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DUPIXENT® (DUPILUMAB)

September 28, 2022 at 5:44 PM EDT

DUPIXENT® (DUPILUMAB) APPROVED BY FDA AS THE FIRST AND ONLY TREATMENT INDICATED FOR PRURIGO NODULARIS

Dupixent significantly reduced itch and skin lesions compared to placebo in direct-to-Phase 3 program consisting of two pivotal trials

About 75,000 adults in the U.S. living with prurigo nodularis are most in need of new treatment options

Approval represents the second dermatology indication for Dupixent and fifth disease indication overall in the U.S.

TARRYTOWN, N.Y. and PARIS, Sept. 28, 2022 /PRNewswire/ -- Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) and Sanofi today announced that the U.S. Food and Drug Administration (FDA) has approved Dupixent® (dupilumab) for the treatment of adult patients with prurigo nodularis. With this approval, Dupixent becomes the first and only medicine specifically indicated to treat prurigo nodularis in the U.S. Prurigo nodularis is a chronic, debilitating skin disease with underlying type 2 inflammation and its impact on quality of life is one of the highest among inflammatory skin diseases. The FDA evaluated the Dupixent application for prurigo nodularis under Priority Review, which is granted to therapies that have the potential to provide significant improvements in the treatment, diagnosis or prevention of serious conditions.

"Patients living with prurigo nodularis must often contend with dozens, if not hundreds, of itchy and painful nodules covering their body and have not had an approved treatment option for their disease," said George D. Yancopoulos, M.D., Ph.D., President and Chief Scientific Officer at Regeneron, and a principal inventor of Dupixent. "Dupixent has already transformed the treatment landscape of several diseases driven by type 2 inflammation – including atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyposis and eosinophilic esophagitis – and been prescribed to more than half a million patients around the world for its approved indications. With this approval, those suffering with prurigo nodularis finally have a medicine to address the debilitating signs and symptoms of the disease."

"Until today, there were limited treatment options to manage the relentless itch and associated sensations of burning and stinging skin that can negatively impact the lives of patients struggling with prurigo nodularis," said Naimish Patel, M.D, Head of Global Development, Immunology and Inflammation at Sanofi. "Dupixent has the potential to transform the standard-of-care for prurigo nodularis patients by alleviating the key hallmarks of the disease, such as reducing itch and achieving clearer skin. With Dupixent now approved in two diseases in dermatology where type 2 inflammation is a central driver, we look forward to further evaluating the potential of inhibiting IL-4 and IL-13 in other chronic skin diseases."

The FDA approval is based on data from two Phase 3 trials, PRIME and PRIME2, evaluating the efficacy and safety of Dupixent in adults with prurigo nodularis. Efficacy in these trials assessed the proportion of subjects with clinically meaningful reduction in itch, clearing of skin, or both:

About three times as many Dupixent patients (60% and 58%) experienced a clinically meaningful reduction in itch from baseline at 24 weeks, compared to 18% and 20% for placebo, the primary endpoint in PRIME
44% and 37% of Dupixent patients experienced a clinically meaningful reduction in itch from baseline at 12 weeks, compared to 16% and 22% for placebo, the primary endpoint in PRIME2
More than twice as many Dupixent patients (48% and 45%) achieved clear or almost clear skin at 24 weeks, compared to 18% and 16% for placebo
More than three times as many Dupixent patients (39% and 32%) experienced both a clinically meaningful reduction in itch and clear or almost clear skin, compared to 9% and 9% of placebo patients at 24 weeks

The safety results of the trial were generally consistent with the known safety profile of Dupixent in its approved dermatology indication. The most common adverse events (≥2%) from pooled PRIME and PRIME2 data more frequently observed with Dupixent than placebo were nasopharyngitis (5% Dupixent, 2% placebo), conjunctivitis (4% Dupixent, 1% placebo), herpes infection (3% Dupixent, 0% placebo), dizziness (3% Dupixent, 1% placebo), muscle pain (3% Dupixent, 1% placebo), and diarrhea (3% Dupixent, 1% placebo).

A regulatory filing for prurigo nodularis is under review by the European Medicines Agency, and submissions to regulatory authorities in additional countries are also planned in 2022.

About the Dupixent Prurigo Nodularis Trials

The PRIME and PRIME2 Phase 3 double-blind, placebo-controlled trials evaluated the efficacy and safety of Dupixent in 311 adults with uncontrolled prurigo nodularis.

In PRIME and PRIME2, the primary endpoint evaluated the proportion of patients with clinically meaningful improvement in itch from baseline (measured by a ≥4-point reduction in Worst-Itch Numeric Rating Scale [WI-NRS] on a 0-10 scale) at 24 and 12 weeks, respectively. Additional endpoints included the proportion of patients with clear or almost clear skin of nodules at 24 weeks (measured by a score of 0 or 1 on the Investigator's Global Assessment PN-Stage [IGA PN-S] on a 0-4 scale), and the proportion of patients who achieved a clinically meaningful response in both WI-NRS and IGA PN-S.

About Dupixent

Dupixent is administered as an injection under the skin (subcutaneous injection) at different injection sites. In patients aged 18 years and older with prurigo nodularis, Dupixent 300 mg is administered with a pre-filled syringe or pre-filled pen every two weeks following an initial loading dose. Dupixent is intended for use under the guidance of a healthcare professional and can be given in a clinic or at home by self-administration after training by a healthcare professional.

Regeneron and Sanofi are committed to helping patients in the U.S. who are prescribed Dupixent gain access to the medicine and receive the support they may need with the DUPIXENT MyWay® program. For more information, please call 1-844-DUPIXENT (1-844-387-4936) or visit www.DUPIXENT.com.

Dupixent has received regulatory approvals in one or more countries around the world for use in certain patients with atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP), eosinophilic esophagitis (EoE) or prurigo nodularis in different age populations. Dupixent is currently approved across these indications in the U.S. and for one or more of these indications in more than 60 countries, including in the European Union and Japan. More than 500,000 patients have been treated with Dupixent globally.

Dupixent, which was invented using Regeneron's proprietary VelocImmune® technology, is a fully human monoclonal antibody that inhibits the signaling of the interleukin-4 (IL-4) and interleukin-13 (IL-13) pathways and is not an immunosuppressant. The Dupixent development program has shown significant clinical benefit and a decrease in type 2 inflammation in Phase 3 trials, establishing that IL-4 and IL-13 are key and central drivers of the type 2 inflammation that plays a major role in multiple related and often co-morbid diseases. These diseases include approved indications for Dupixent such as prurigo nodularis, atopic dermatitis, asthma, CRSwNP and EoE.

About Regeneron's VelocImmune Technology

Regeneron's VelocImmune technology utilizes a proprietary genetically engineered mouse platform endowed with a genetically humanized immune system to produce optimized fully human antibodies. When Regeneron's co-Founder, President and Chief Scientific Officer George D. Yancopoulos was a graduate student with his mentor Frederick W. Alt in 1985, they were the first to envision making such a genetically humanized mouse, and Regeneron has spent decades inventing and developing VelocImmune and related VelociSuite® technologies. Dr. Yancopoulos and his team have used VelocImmune technology to create approximately one in five of all original, FDA-approved or authorized fully human monoclonal antibodies. This includes REGEN-COV® (casirivimab and imdevimab), Dupixent, Libtayo® (cemiplimab-rwlc), Praluent® (alirocumab), Kevzara® (sarilumab), Evkeeza® (evinacumab-dgnb) and Inmazeb™ (atoltivimab, maftivimab and odesivimab-ebgn).

Dupilumab Development Program

Dupilumab is being jointly developed by Regeneron and Sanofi under a global collaboration agreement. To date, dupilumab has been studied across more than 60 clinical trials involving more than 10,000 patients with various chronic diseases driven in part by type 2 inflammation.

In addition to the currently approved indications, Regeneron and Sanofi are studying dupilumab in a broad range of diseases driven by type 2 inflammation or other allergic processes in Phase 3 trials, including pediatric eosinophilic esophagitis, hand and foot atopic dermatitis, chronic inducible urticaria-cold, chronic spontaneous urticaria, chronic pruritis of unknown origin, chronic obstructive pulmonary disease with evidence of type 2 inflammation, chronic rhinosinusitis without nasal polyposis, allergic fungal rhinosinusitis, allergic bronchopulmonary aspergillosis and bullous pemphigoid. These potential uses of dupilumab are currently under clinical investigation, and the safety and efficacy in these conditions have not been fully evaluated by any regulatory authority.

https://www.dupixent.com/

INDICATIONS

DUPIXENT is a prescription medicine used:

to treat adults and children 6 months of age and older with moderate-to-severe eczema (atopic dermatitis or AD) that is not well controlled with prescription therapies used on the skin (topical), or who cannot use topical therapies. DUPIXENT can be used with or without topical corticosteroids. It is not known if DUPIXENT is safe and effective in children with atopic dermatitis under 6 months of age.
with other asthma medicines for the maintenance treatment of moderate-to-severe eosinophilic or oral steroid dependent asthma in adults and children 6 years of age and older whose asthma is not controlled with their current asthma medicines. DUPIXENT helps prevent severe asthma attacks (exacerbations) and can improve your breathing. DUPIXENT may also help reduce the amount of oral corticosteroids you need while preventing severe asthma attacks and improving your breathing. DUPIXENT is not used to treat sudden breathing problems. It is not known if DUPIXENT is safe and effective in children with asthma under 6 years of age.
with other medicines for the maintenance treatment of chronic rhinosinusitis with nasal polyposis (CRSwNP) in adults whose disease is not controlled. It is not known if DUPIXENT is safe and effective in children with chronic rhinosinusitis with nasal polyposis under 18 years of age.
to treat adults and children 12 years of age and older, who weigh at least 88 pounds (40 kg), with eosinophilic esophagitis (EoE). It is not known if DUPIXENT is safe and effective in children with eosinophilic esophagitis under 12 years of age and who weigh at least 88 pounds (40 kg).
to treat adults with prurigo nodularis (PN). It is not known if DUPIXENT is safe and effective in children with prurigo nodularis under 18 years of age.

About Regeneron Regeneron is a leading biotechnology company that invents, develops and commercializes life-transforming medicines for people with serious diseases. Founded and led for nearly 35 years by physician-scientists, our unique ability to repeatedly and consistently translate science into medicine has led to nine FDA-approved treatments and numerous product candidates in development, almost all of which were homegrown in our laboratories. Our medicines and pipeline are designed to help patients with eye diseases, allergic and inflammatory diseases, cancer, cardiovascular and metabolic diseases, pain, hematologic conditions, infectious diseases and rare diseases.

Regeneron is accelerating and improving the traditional drug development process through our proprietary VelociSuite® technologies, such as VelocImmune®, which uses unique genetically humanized mice to produce optimized fully human antibodies and bispecific antibodies, and through ambitious research initiatives such as the Regeneron Genetics Center®, which is conducting one of the largest genetics sequencing efforts in the world.

For more information, please visit www.Regeneron.com or follow @Regeneron on Twitter.

About Sanofi
We are an innovative global healthcare company, driven by one purpose: we chase the miracles of science to improve people's lives. Our team, across some 100 countries, is dedicated to transforming the practice of medicine by working to turn the impossible into the possible. We provide potentially life-changing treatment options and life-saving vaccine protection to millions of people globally, while putting sustainability and social responsibility at the center of our ambitions.

Sanofi is listed on EURONEXT: SAN and NASDAQ: SNY.

View original content:https://www.prnewswire.com/news-releases/dupixent-dupilumab-approved-by-fda-as-the-first-and-only-treatment-indicated-for-prurigo-nodularis-301636139.html

SOURCE Regeneron Pharmaceuticals, Inc.

Sanofi, Regeneron win FDA label expansion for Dupixent in chronic, skin condition

Sep. 29, 2022 6:51 AM ET

Regeneron Pharmaceuticals, Inc. (REGN), SNYSNYNF, GCVRX

By: Dulan Lokuwithana, SA News Editor

The FDA has approved Dupixent, developed by Regeneron (NASDAQ:REGN) and Sanofi (NASDAQ:SNY) (OTCPK:SNYNF) (GCVRX), for adults with prurigo nodularis, a chronic, inflammatory skin condition.
https://seekingalpha.com/news/3887050-sanofi-regeneron-win-fda-label-expansion-for-dupixent-in-chronic-skin-condition
https://seekingalpha.com/symbol/SNY
https://seekingalpha.com/symbol/REGN
https://www.regeneron.com/
https://www.dupixent.com/

Indications DUPIXENT is a prescription medicine used: to treat adults and children 6 months of age and older with moderate-to-severe atopic dermatitis (eczema) that is not well controlled with prescription therapies used on the skin (topical), or who cannot use topical therapies. DUPIXENT can be used with or without topical corticosteroids. It is not known if DUPIXENT is safe and effective in children with atopic dermatitis under 6 months of age. with other asthma medicines for the maintenance treatment of moderate-to-severe eosinophilic or oral steroid dependent asthma in adults and children 6 years of age and older whose asthma is not controlled with their current asthma medicines. DUPIXENT helps prevent severe asthma attacks (exacerbations) and can improve your breathing. DUPIXENT may also help reduce the amount of oral corticosteroids you need while preventing severe asthma attacks and improving your breathing. DUPIXENT is not used to treat sudden breathing problems. It is not known if DUPIXENT is safe and effective in children with asthma under 6 years of age. with other medicines for the maintenance treatment of chronic rhinosinusitis with nasal polyposis (CRSwNP) in adults whose disease is not controlled. It is not known if DUPIXENT is safe and effective in children with chronic rhinosinusitis with nasal polyposis under 18 years of age. to treat adults and children 12 years of age and older, who weigh at least 88 pounds (40 kg), with eosinophilic esophagitis (EoE). It is not known if DUPIXENT is safe and effective in children with eosinophilic esophagitis under 12 years of age and who weigh at least 88 pounds (40 kg).

BIOTECNOVA™

KEYTRUDA® (pembrolizumab)

LYNPARZA® (olaparib) tablets

Merck’s KEYTRUDA® (pembrolizumab) Receives Four New Approvals in Japan, Including in High-Risk Early-Stage Triple-Negative Breast Cancer (TNBC)

September 27, 2022 6:45 am ET

KEYTRUDA now approved for 23 uses in 13 different types of cancer in Japan

RAHWAY, N.J.--(BUSINESS WIRE)-- Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced that KEYTRUDA, Merck’s anti-PD-1 therapy, received four new approvals from Japan’s Ministry of Health, Labor and Welfare (MHLW):

KEYTRUDA in combination with chemotherapy as neoadjuvant treatment, and then continued as monotherapy as adjuvant treatment after surgery for patients with hormone receptor-negative and human epidermal growth factor receptor 2 (HER2)-negative breast cancer at high risk of recurrence, based on data from the KEYNOTE-522 trial;
KEYTRUDA as monotherapy for the adjuvant treatment of certain patients with renal cell carcinoma (RCC) at increased risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions, based on data from the KEYNOTE-564 trial;
KEYTRUDA in combination with chemotherapy, with or without bevacizumab, for the treatment of patients with advanced or recurrent cervical cancer with no prior chemotherapy who are not amenable to curative treatment, based on data from the KEYNOTE-826 trial, and;
KEYTRUDA as monotherapy for the adjuvant treatment of patients with stage IIB or IIC melanoma after complete resection, based on data from the KEYNOTE-716 trial.

“Based on compelling data from our clinical trial program, KEYTRUDA has become an important treatment option in Japan and now has 23 approved uses across 13 different types of cancer,” said Dr. Eliav Barr, senior vice president, head of global clinical development and chief medical officer, Merck Research Laboratories. “These four new approvals provide certain patients with advanced or recurrent cervical cancer, high-risk early-stage triple-negative breast cancer, renal cell carcinoma and completely resected stage IIB and IIC melanoma the opportunity to be treated with KEYTRUDA.”

“In Japan, the cancer mortality rate continues to rise annually, and patients are in need of new treatment options – particularly those with breast cancer, which is the most prevalent cancer among women in the country,” said Kyle Tattle, Representative Director and President, MSD Japan. “These new approvals for KEYTRUDA are the result of strong collaboration with the MHLW and provide additional treatment options for appropriate patients with difficult-to-treat cancers.”

Approval as neoadjuvant and adjuvant treatment regimen for triple-negative breast cancer
The approval of KEYTRUDA plus chemotherapy as neoadjuvant treatment, and then continued as monotherapy as adjuvant treatment after surgery for patients with hormone receptor-negative and HER2-negative breast cancer at high risk of recurrence is based on results from the Phase 3 KEYNOTE-522 trial, in which KEYTRUDA in combination with chemotherapy before surgery and continued as a single agent after surgery resulted in a statistically significant and clinically meaningful improvement in event-free survival (EFS), reducing the risk of disease progression that precludes curative surgery, local or distant recurrence, second primary malignancy or death by 37% (HR=0.63 [95% CI, 0.48-0.82]; p=0.00031) compared to neoadjuvant placebo in combination with chemotherapy and adjuvant placebo alone after surgery in these patients.

The Japanese package insert states that in KEYNOTE-522, adverse reactions were observed in 774 patients (98.9%) out of the safety analysis set of 783 patients (including 45/45 Japanese patients) receiving KEYTRUDA at a dose of 200 mg every three weeks in combination with chemotherapy as neoadjuvant treatment, and then continued as monotherapy as adjuvant treatment after surgery. The most common adverse reactions (≥20%) were nausea (63.2%), alopecia (60.2%), anemia (54.8%), neutropenia (46.9%), fatigue (42.1%), diarrhea (30.4%), elevated alanine aminotransferase (26.1%), vomiting (25.5%), asthenia (25.3%), rash (25.0%), constipation (24.0%), decreased neutrophil count (23.6%) and elevated aspartate aminotransferase (20.1%).

Triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer, which has the highest risk of recurrence within the first five years after diagnosis and is associated with worse outcomes compared to other forms of breast cancer. While some breast cancers may test positive for estrogen receptors, progesterone receptors or overexpression of HER2, TNBC tests negative for all three. Triple-negative breast cancer is known to be prevalent in Japan, as approximately 15% of patients with breast cancer in Japan are diagnosed with TNBC. Breast cancer is the most commonly diagnosed cancer in women in Japan, with more than 94,000 people diagnosed in 2020.

Approval in renal cell carcinoma
The approval of KEYTRUDA for the adjuvant treatment of certain patients with RCC at increased risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions is based on results from the Phase 3 KEYNOTE-564 trial, in which KEYTRUDA as adjuvant treatment demonstrated a statistically significant improvement in disease-free survival, reducing the risk of disease recurrence or death by 32% (HR=0.68 [95% CI, 0.53-0.87]; p=0.0010) compared to placebo.

The Japanese package insert states that in KEYNOTE-564, adverse reactions were observed in 386 patients (79.1%) out of the safety analysis set of 488 patients receiving KEYTRUDA at a dose of 200 mg every three weeks or 400 mg every six weeks for up to 12 months. The most common adverse reactions (≥10%) were fatigue (20.3%), pruritus (18.6%), hypothyroidism (17.6%), diarrhea (15.8%), rash (15.0%) and hyperthyroidism (10.2%).

Renal cell carcinoma is by far the most common type of kidney cancer; about nine out of 10 kidney cancer diagnoses are RCCs. Renal cell carcinoma is about twice as common in men than in women. In Japan, it is estimated there were more than 25,000 new cases of kidney cancer diagnosed and more than 8,000 deaths from the disease in 2020.

Approval in advanced cervical cancer
The approval for KEYTRUDA plus chemotherapy, with or without bevacizumab, for the treatment of patients with advanced or recurrent cervical cancer with no prior chemotherapy who are not amenable to curative treatment is based on results from the Phase 3 KEYNOTE-826 trial, in which KEYTRUDA plus chemotherapy, with or without bevacizumab, demonstrated a statistically significant improvement in overall survival, reducing the risk of death by 33% (HR=0.67 [95% CI, 0.54-0.84]; p=0.0003), and progression-free survival, reducing the risk of disease progression or death by 35% (HR=0.65 [95% CI, 0.53-0.79]; p<0.0001), compared to chemotherapy with or without bevacizumab in these patients.

The Japanese package insert states that in KEYNOTE-826, adverse reactions were observed in 298 patients (97.1%) out of the safety analysis set of 307 patients (including 35/35 Japanese patients) receiving KEYTRUDA at a dose of 200 mg every three weeks in combination with investigator’s choice of anti-cancer regimens. The most common adverse reactions (≥20%) were alopecia (55.7%), anemia (48.5%), nausea (33.9%), diarrhea (24.8%), peripheral neuropathy (24.4%), fatigue (22.8%), peripheral sensory neuropathy (22.5%), neutropenia (22.1%) and vomiting (20.5%).

Cervical cancer forms in the lower part of the uterus and in the cells lining the cervix. All women are at risk for cervical cancer, and the disease is most frequently diagnosed between the ages of 35 to 44. In Japan, it is estimated there were more than 12,700 new cases of cervical cancer diagnosed and nearly 4,200 deaths from the disease in 2020.

Expanded indication in the adjuvant treatment of melanoma
The expanded indication for KEYTRUDA as monotherapy for the adjuvant treatment of patients with stage IIB or IIC melanoma after complete resection is based on results of the Phase 3 KEYNOTE-716 trial, in which KEYTRUDA as adjuvant treatment significantly prolonged recurrence-free survival, reducing the risk of disease recurrence or death by 35% (HR=0.65 [95% CI, 0.46-0.92]; p=0.00658) compared to placebo in these patients. With this expansion, Keytruda is now approved for the adjuvant treatment of resected stage IIB, IIC and stage III melanoma.

The Japanese package insert states that in KEYNOTE-716, adverse reactions were observed in 400 patients (82.8%) out of the safety analysis set of 483 patients (including 2/2 Japanese patients) receiving KEYTRUDA at a dose of 200 mg every three weeks. The most common adverse reactions (≥10%) were pruritus (24.2%), fatigue (21.1%), diarrhea (18.6%), arthralgia (16.1%), rash (15.7%) and hypothyroidism (15.5%).

Melanoma, the most serious form of skin cancer, is characterized by the uncontrolled growth of pigment-producing cells. In Japan, the rates of skin cancer have been rapidly increasing, and it is estimated there were more than 1,500 new cases of melanoma diagnosed and nearly 700 deaths from the disease in Japan in 2020.

About KEYTRUDA® (pembrolizumab) injection, 100 mg
KEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Merck has the industry’s largest immuno-oncology clinical research program. There are currently more than 1,600 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.

Selected KEYTRUDA® (pembrolizumab) Indications in the U.S.
Melanoma
KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.

KEYTRUDA is indicated for the adjuvant treatment of adult and pediatric (12 years and older) patients with stage IIB, IIC, or III melanoma following complete resection.

Non-Small Cell Lung Cancer
KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [tumor proportion score (TPS) ≥1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is:

stage III where patients are not candidates for surgical resection or definitive chemoradiation, or
metastatic.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.

Head and Neck Squamous Cell Cancer
KEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [Combined Positive Score (CPS) ≥1] as determined by an FDA-approved test.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy.

Classical Hodgkin Lymphoma
KEYTRUDA is indicated for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL).

KEYTRUDA is indicated for the treatment of pediatric patients with refractory cHL, or cHL that has relapsed after 2 or more lines of therapy.

Primary Mediastinal Large B-Cell Lymphoma
KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy.

KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.

Urothelial Carcinoma
KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC):

who are not eligible for any platinum-containing chemotherapy, or
who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

Non-muscle Invasive Bladder Cancer
KEYTRUDA is indicated for the treatment of patients with Bacillus Calmette-Guerin-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.

Microsatellite Instability-High or Mismatch Repair Deficient Cancer
KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options.

Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer
KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC) as determined by an FDA-approved test.

Gastric Cancer
KEYTRUDA, in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of patients with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma.

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Esophageal Cancer
KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic esophageal or gastroesophageal junction (GEJ) (tumors with epicenter 1 to 5 centimeters above the GEJ) carcinoma that is not amenable to surgical resection or definitive chemoradiation either:

in combination with platinum- and fluoropyrimidine-based chemotherapy, or
as a single agent after one or more prior lines of systemic therapy for patients with tumors of squamous cell histology that express PD-L1 (CPS ≥10) as determined by an FDA-approved test.

Cervical Cancer
KEYTRUDA, in combination with chemotherapy, with or without bevacizumab, is indicated for the treatment of patients with persistent, recurrent, or metastatic cervical cancer whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.

Hepatocellular Carcinoma
KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Merkel Cell Carcinoma
KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC). This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Renal Cell Carcinoma
KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC).

KEYTRUDA is indicated for the adjuvant treatment of patients with RCC at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions.

Endometrial Carcinoma
KEYTRUDA, as a single agent, is indicated for the treatment of patients with advanced endometrial carcinoma that is MSI-H or dMMR, as determined by an FDA-approved test, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.

Tumor Mutational Burden-High Cancer
KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [≥10 mutations/megabase] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with TMB-H central nervous system cancers have not been established.

Cutaneous Squamous Cell Carcinoma
KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) or locally advanced cSCC that is not curable by surgery or radiation.

Triple-Negative Breast Cancer
KEYTRUDA is indicated for the treatment of patients with high-risk early-stage triple-negative breast cancer (TNBC) in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.

KEYTRUDA, in combination with chemotherapy, is indicated for the treatment of patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 (CPS ≥10) as determined by an FDA-approved test.

https://www.keytruda.com/

Merck’s focus on cancer
Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck, the potential to bring new hope to people with cancer drives our purpose and supporting accessibility to our cancer medicines is our commitment. As part of our focus on cancer, Merck is committed to exploring the potential of immuno-oncology with one of the largest development programs in the industry across more than 30 tumor types. We also continue to strengthen our portfolio through strategic acquisitions and are prioritizing the development of several promising oncology candidates with the potential to improve the treatment of advanced cancers. For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.

About Merck
At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.merck.com and connect with us on Twitter, Facebook, Instagram, YouTube and LinkedIn.

Please see Prescribing Information for KEYTRUDA (pembrolizumab) at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf and Medication Guide for KEYTRUDA at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_mg.pdf .

Source: Merck & Co., Inc.

Merck wins four new approvals for Keytruda in Japan

Sep. 27, 2022 7:16 AM ET

Merck & Co., Inc. (MRK)

By: Dulan Lokuwithana, SA News Editor3 Comments

Merck (NYSE:MRK) announced Wednesday that Japan's Ministry of Health approved its blockbuster for four new indications, increasing the treatment's licensure in the country to 23 approved uses across 13 cancer types.
https://seekingalpha.com/news/3886260-merck-wins-four-new-approvals-for-keytruda-in-japan
https://seekingalpha.com/symbol/MRK
https://www.keytruda.com/
https://www.merck.com/

A BREAKTHROUGH IMMUNOTHERAPY THAT MAY HELP YOU FACE YOUR CANCER IT’S TRU. KEYTRUDA. SELECT A TYPE OF CANCER Search by cancer type or name Advanced non–small cell lung cancer Melanoma Head and neck squamous cell cancer High-risk non-muscle invasive bladder cancer (NMIBC) Advanced urothelial bladder cancer Kidney cancer (RCC) Advanced MSI-H/dMMR colorectal cancer Microsatellite instability-high cancer (MSI-H/dMMR) High-risk early-stage triple-negative breast cancer (TNBC) Advanced triple-negative breast cancer (TNBC) Classical Hodgkin lymphoma (cHL) Advanced gastric cancer Advanced cervical cancer Advanced MSI-H/dMMR endometrial cancer Primary mediastinal B-cell lymphoma (PMBCL) Advanced liver cancer (HCC) Advanced Merkel cell carcinoma Advanced esophageal cancer Cutaneous squamous cell carcinoma (cSCC)

LYNPARZA® (olaparib) tablets

Lynparza approved in China as 1st-line maintenance treatment with bevacizumab for HRD-positive advanced ovarian cancer

PUBLISHED22 September 2022 22 September 2022 07:00 BST

One in two women with advanced ovarian cancer has an HRD-positive tumour

AstraZeneca and MSD’s Lynparza (olaparib) has been approved in China for the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to 1st-line platinum-based chemotherapy in combination with bevacizumab, and whose cancer is associated with homologous recombination deficiency (HRD)-positive status.

In China, ovarian cancer is the third most common gynaecologic cancer, with a five-year survival rate of approximately 39%, largely because more than 70% of women are diagnosed with advanced disease (Stage III or IV).1,2 In 2020, there were over 55,000 new cases of ovarian cancer in China.3

The approval by China's National Medical Products Administration was based on an HRD-positive subgroup exploratory analysis of the PAOLA-1 Phase III trial which showed Lynparza plus bevacizumab demonstrated a substantial progression-free survival (PFS) improvement versus bevacizumab alone for patients with HRD-positive advanced ovarian cancer. During European Society for Medical Oncology Congress (ESMO) 2022, the final overall survival (OS) results were presented from the PAOLA-1 Phase III trial demonstrating that Lynparza plus bevacizumab provided a clinically meaningful improvement in overall survival in HRD-positive advanced ovarian cancer.

Professor Ding Ma, Member of the Chinese Academy of Engineering, said: “Ovarian cancer has the highest fatality rate among gynaecologic cancers in China. The emergence of PARP inhibitors and their application in the 1st-line treatment of ovarian cancer could help patients delay disease progression and achieve long-term remission. In the PAOLA-1 trial, the combination of olaparib and bevacizumab demonstrated clinically meaningful improvements in overall survival. This approval provides HRD-positive patients with a new option for 1st-line maintenance therapy.”

Professor Beihua Kong, Chairman of the Gynaecological Oncology Branch of the Chinese Medical Association, said: "Ovarian cancer has entered the era of precision medicine, and HRD detection (including BRCA1/2 mutations) has important clinical value for newly diagnosed patients with advanced ovarian cancer, to help guide first-line treatment decisions. The approval of the combination of olaparib and bevacizumab brings a clinically meaningful survival benefit to HRD-positive patients, and further reflects the importance of a precision approach to help guide treatment decisions in ovarian cancer."

Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: “The maintenance treatment of Lynparza in combination with bevacizumab has shown to both improve progression-free survival and provide a clinically meaningful improvement in overall survival in patients with HRD-positive advanced ovarian cancer following response to platinum-based chemotherapy. I am thrilled we can now bring this targeted treatment option to these patients in China.”

Dr Eliav Barr, Senior Vice President, Head of Global Clinical Development and Chief Medical Officer, MSD Research Laboratories, said: “This approval is an important milestone for patients with newly diagnosed advanced ovarian cancer in China and underscores the critical importance of HRD testing for all women with advanced ovarian cancer at the point of diagnosis.”

The initial results from the PAOLA-1 Phase III trial showed that Lynparza plus bevacizumab reduced the risk of disease progression or death by 67% in the subgroup of patients with HRD-positive advanced ovarian cancer (based on a hazard ratio [HR] of 0.33; 95% confidence interval [CI] 0.25-0.45 from the pre-specified exploratory analysis). The primary endpoint in the intent-to-treat population was a statistically significant and clinically meaningful improvement in PFS. The data from the PAOLA-1 trial was published in The New England Journal of Medicine in 2019.

Further results from the five-year analysis of the PAOLA-1 trial recently presented at the ESMO 2022 showed Lynparza plus bevacizumab increased median overall survival to 56.5 months versus 51.6 months with bevacizumab alone, in patients with newly diagnosed advanced ovarian cancer irrespective of HRD status. This increase was not statistically significant. In HRD-positive patients, Lynparza plus bevacizumab provided a clinically meaningful improvement in overall survival, reducing the risk of death by 38% versus bevacizumab (based on a HR of 0.62; 95% CI 0.45-0.85 from the pre-specified exploratory sub-group analysis) despite PAOLA-1 having 30% Stage IV patients. The safety and tolerability profile of Lynparza in this trial was in line with that observed in prior clinical trials, with no new safety signals.

Lynparza in combination with bevacizumab is approved in the US, and several other countries as a 1st-line maintenance treatment for patients with HRD-positive advanced ovarian cancer and is currently under regulatory review in other countries around the world. In China, Lynparza is approved for the treatment of BRCA-mutated metastatic castration-resistant prostate cancer as well as a 1st-line maintenance therapy in BRCA-mutated advanced ovarian cancer.

PAOLA-1
PAOLA-1 is a double-blinded Phase III trial testing the efficacy and safety of Lynparza added to standard of care bevacizumab versus bevacizumab alone, as a 1st-line maintenance treatment for newly diagnosed advanced FIGO Stage III-IV high-grade serous or endometroid ovarian, fallopian tube, or peritoneal cancer patients who had a complete or partial response to 1st-line treatment with platinum-based chemotherapy and bevacizumab. AstraZeneca and MSD announced in August 2019 that the trial met its primary endpoint of PFS in the overall trial population.

The primary analysis of the PAOLA-1 Phase III trial showed that Lynparza, in combination with bevacizumab maintenance treatment, reduced the risk of disease progression or death by 67% (based on a HR of 0.33; 95% CI 0.25-0.45) in the subgroup of patients with HRD-positive advanced ovarian cancer. The addition of Lynparza improved PFS to a median of 46.8 months versus 17.6 with bevacizumab alone in this patient population.

Updated results from the five-year analysis of the PAOLA-1 Phase III trial demonstrate that in a pre-specified exploratory subgroup analysis of HRD-positive patients, Lynparza plus bevacizumab provided a clinically meaningful improvement in overall survival, reducing the risk of death by 38% versus bevacizumab (based on a HR of 0.62; 95% CI 0.45-0.85). In addition, 65.5% of patients treated with Lynparza plus bevacizumab were still alive at five years versus 48.4% of those treated with bevacizumab alone. Lynparza plus bevacizumab also improved median PFS to almost four years (46.8 months) versus 17.6 months with bevacizumab plus placebo, and 46.1% of patients treated with Lynparza plus bevacizumab remain progression free at five years versus 19.2% of patients treated with bevacizumab alone.

PAOLA-1 is an ENGOT (European Network of Gynaecological Oncological Trial groups) trial, sponsored by ARCAGY Research (Association de Recherche sur les CAncers dont GYnécologiques) on behalf of GINECO (Groupe d’Investigateurs National des Etudes des Cancers Ovariens et du sein), lead group for the PAOLA-1 trial. ARCAGY-GINECO is an academic group specialising in clinical and translational research in patients’ gynaecological cancers, labelled by the French National Cancer Institute (INCa), and a member of the GCIG (Gynecologic Cancer InterGroup).

Homologous recombination deficiency
HRD, which defines a subgroup of ovarian cancer, encompasses a wide range of genetic abnormalities, including BRCA mutations and beyond. As with BRCA gene mutations, HRD interferes with normal cell DNA repair mechanisms and confers sensitivity to PARP inhibitors including Lynparza.13

Lynparza
Lynparza (olaparib) is a 1st-in-class PARP inhibitor and the first targeted treatment to block DNA damage response (DDR) in cells/tumours harbouring a deficiency in homologous recombination repair (HRR), such as mutations in BRCA1 and/or BRCA2. Inhibition of PARP with Lynparza leads to the trapping of PARP bound to DNA single-strand breaks, stalling of replication forks, their collapse and the generation of DNA double-strand breaks and cancer cell death. Lynparza is being tested in a range of PARP-dependent tumour types with defects and dependencies in the DDR pathway.

Lynparza is currently approved in a number of countries across multiple tumour types including maintenance treatment of platinum-sensitive relapsed ovarian cancer and as both monotherapy and in combination with bevacizumab for the 1st-line maintenance treatment of BRCA-mutated (BRCAm) and HRD-positive advanced ovarian cancer, respectively; for gBRCAm, HER2-negative metastatic breast cancer (in the EU and Japan this includes locally advanced breast cancer); for gBRCAm, HER2-negative high-risk early breast cancer (in Japan this includes all BRCAm HER2-negative high-risk early breast cancer); for gBRCAm metastatic pancreatic cancer; and HRR gene-mutated metastatic castration-resistant prostate cancer (BRCAm only in the EU and Japan). In China, Lynparza is approved for the treatment of BRCA-mutated metastatic castration-resistant prostate cancer as well as a 1st-line maintenance therapy in BRCA-mutated advanced ovarian cancer.

Lynparza, which is being jointly developed and commercialised by AstraZeneca and MSD, has been used to treat over 75,000 patients worldwide. Lynparza has a broad clinical trial development programme, and AstraZeneca and MSD are working together to understand how it may affect multiple PARP-dependent tumours as a monotherapy and in combination across multiple cancer types. Lynparza is the foundation of AstraZeneca's industry-leading portfolio of potential new medicines targeting DDR mechanisms in cancer cells.

https://www.lynparza.com/

The AstraZeneca and MSD strategic oncology collaboration
In July 2017, AstraZeneca and Merck & Co., Inc., Kenilworth, NJ, US, known as MSD outside the US and Canada, announced a global strategic oncology collaboration to co-develop and co-commercialise Lynparza, the world’s first PARP inhibitor, and Koselugo (selumetinib), a MEK inhibitor, for multiple cancer types. Working together, the companies will develop Lynparza and Koselugo in combination with other potential new medicines and as monotherapies. Independently, the companies will develop Lynparza and Koselugo in combination with their respective PD-L1 and PD-1 medicines.

AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.

The Company's focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience.

By harnessing the power of six scientific platforms – Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response, Antibody Drug Conjugates, Epigenetics, and Cell Therapies – and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and, one day, eliminate cancer as a cause of death.

AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on Twitter @AstraZeneca.

AstraZeneca/Merck's Lynparza gets approval in China for ovarian cancer subtype

Sep. 22, 2022 4:23 AM ET

AstraZeneca PLC (AZN), MRK

By: Ravikash, SA News Editor1 Comment

AstraZeneca (NASDAQ:AZN) and Merck's (NYSE:MRK) Lynparza was approved in China as a maintenance therapy for certain patients with a type of ovarian cancer.
https://seekingalpha.com/news/3885135-astrazenecamercks-lynparza-gets-approval-in-china-for-ovarian-cancer-subtype
https://seekingalpha.com/symbol/AZN
https://seekingalpha.com/symbol/MRK
https://www.lynparza.com/

WHAT IS LYNPARZA? LYNPARZA is a prescription medicine used to treat adults who have: advanced ovarian cancer, fallopian tube cancer, or primary peritoneal cancer with a certain type of inherited (germline) or acquired (somatic) abnormal BRCA gene. LYNPARZA is used alone as maintenance treatment after the cancer has responded to your first treatment with platinum-based chemotherapy. Your healthcare provider will perform a test to make sure that LYNPARZA is right for you advanced ovarian cancer, fallopian tube cancer, or primary peritoneal cancer with a certain type of abnormal BRCA gene or a positive laboratory tumor test for genomic instability called HRD. LYNPARZA is used in combination with another anti-cancer medicine, bevacizumab, as maintenance treatment after the cancer has responded to your first treatment with platinum-based chemotherapy. Your healthcare provider will perform a test to make sure that LYNPARZA is right for you ovarian cancer, fallopian tube cancer, or primary peritoneal cancer, as maintenance treatment, when the cancer has come back. LYNPARZA is used after the cancer has responded to treatment with platinum-based chemotherapy human epidermal growth factor receptor 2 (HER2)-negative early breast cancer with a certain type of inherited (germline) abnormal BRCA gene. LYNPARZA is given after surgery (treatment after surgery is called adjuvant therapy). You should have received chemotherapy medicines before or after surgery to remove the tumor. Your healthcare provider will perform a test to make sure that LYNPARZA is right for you a certain type of abnormal inherited BRCA gene, human epidermal growth factor receptor 2 (HER2)-negative breast cancer that has spread to other parts of the body (metastatic). You should have received chemotherapy medicines, either before or after your cancer has spread. If you have hormone receptor (HR)-positive disease, you should have been treated with hormonal therapy. Your healthcare provider will perform a test to make sure that LYNPARZA is right for you metastatic pancreatic cancer with a certain type of abnormal inherited BRCA gene. LYNPARZA is used as a maintenance treatment after your cancer has not progressed on at least 16 weeks of treatment with platinum-based chemotherapy. Your healthcare provider will perform a test to make sure LYNPARZA is right for you prostate cancer with certain inherited or acquired abnormal genes called homologous recombination repair (HRR genes). LYNPARZA is used when the cancer has spread to other parts of the body (metastatic), and no longer responds to a medical or surgical treatment that lowers testosterone, and has progressed after treatment with enzalutamide or abiraterone. Your healthcare provider will perform a test to make sure LYNPARZA is right for you It is not known if LYNPARZA is safe and effective in children.

ZEJULA (niraparib) capsules

LYNPARZA® (olaparib) tablets

ZEJULA (niraparib) capsules

22 September 2022

Oncologic Drugs Advisory Committee to review Zejula overall survival data from the NOVA phase III trial in recurrent ovarian cancer

Issued: London UK

For media and investors only

GSK plc (LSE/NYSE: GSK) today announced that the US Food and Drug Administration (FDA) will convene a meeting of the Oncologic Drugs Advisory Committee (ODAC) to discuss overall survival (OS) data from the ENGOT-OV16/NOVA phase III clinical trial. NOVA is a randomised, double-blind, placebo-controlled phase III trial of Zejula (niraparib), an oral, once-daily poly (ADP-ribose) polymerase (PARP) inhibitor for the maintenance treatment of women with platinum-sensitive recurrent ovarian cancer.

The phase III NOVA trial met the primary endpoint of progression-free survival (PFS) in both the gBRCAm and non-gBRCAm cohorts, demonstrating a statistically significant and clinically meaningful treatment effect of Zejula in this patient population, regardless of biomarker status. These PFS results served as the primary basis for the US FDA approval for the maintenance treatment of women with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy. Overall survival was a secondary endpoint. Updated final overall survival data was recently shared with the FDA.

Hesham Abdullah, SVP, Global Head of Oncology Development, GSK said: “We believe PARP inhibitors, including Zejula, are important options for the maintenance treatment of patients with recurrent ovarian cancer, across all biomarker subgroups, who are in complete or partial response to platinum-based chemotherapy. We look forward to continuing our ongoing discussions with the FDA.”

The ODAC meeting is scheduled for 22 November 2022. This is not related to the niraparib indication in the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to first-line platinum-based chemotherapy.

About ovarian cancer

Ovarian cancer is the eighth most common cancer in women worldwide. [1] Despite high response rates to platinum-based chemotherapy in the front-line setting, approximately 85% of patients will experience disease recurrence.[2] Once the disease recurs, it is rarely curable, with decreasing time intervals to each subsequent recurrence.

About Zejula (niraparib)

Zejula is an oral, once-daily PARP inhibitor currently being evaluated in multiple pivotal trials. GSK is building a robust clinical development programme by assessing activity across multiple tumour types and evaluating several potential combinations of Zejula with other therapeutics. The ongoing development programme includes several combination studies.

ZEJULA is indicated:

for the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to first-line platinum-based chemotherapy
for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy
https://zejula.com/
https://www.zejulahcp.com/

Please see accompanying US Prescribing Information.

About GSK

GSK is a global biopharma company with a purpose to unite science, technology, and talent to get ahead of disease together. Find out more at gsk.com/company.

FDA panel to review GSK Zejula's overall survival data in recurrent ovarian cancer

Sep. 23, 2022 5:04 AM ET

GSK plc (GSK)

By: Ravikash, SA News Editor

GSK (NYSE:GSK) said on Sept. 22 that a panel of the U.S. Food and Drug Administration (FDA) is scheduled to hold a meeting on Nov. 22 to discuss overall survival (OS) data from a phase 3 trial of Zejula (niraparib) for recurrent ovarian cancer.

https://seekingalpha.com/news/3885526-fda-panel-to-review-gsk-zejulas-overall-survival-data-in-recurrent-ovarian-cancer

https://seekingalpha.com/symbol/GSK

https://zejula.com/

https://www.zejulahcp.com/

https://us.gsk.com/en-us/

Approved Use ZEJULA is a prescription medicine used for the maintenance treatment of adults with advanced ovarian cancer, fallopian tube cancer, or primary peritoneal cancer. ZEJULA is used after the cancer has responded (complete or partial response) to treatment with platinum-based chemotherapy. It is not known if ZEJULA is safe and effective in children.

Retevmo® (selpercatinib)

TUKYSA® (tucatinib) in Combination with Trastuzumab

ZEJULA (niraparib) capsules

FDA Approves Lilly's Retevmo® (selpercatinib), the First and Only RET Inhibitor for Adults with Advanced or Metastatic Solid Tumors with a RET Gene Fusion, Regardless of Type

September 21, 2022Download PDF

Tumor-agnostic data supporting approval demonstrated an overall response rate (ORR) of 44% across multiple tumor types

FDA simultaneously grants traditional approval in adults with locally advanced or metastatic non-small cell lung cancer (NSCLC) with a RET gene fusion, as detected by an FDA-approved test

INDIANAPOLIS, Sept. 21, 2022 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY) today announced the U.S. Food and Drug Administration (FDA) has granted approval to Retevmo® (selpercatinib, 40 mg & 80 mg capsules) for adult patients with locally advanced or metastatic solid tumors with a rearranged during transfection (RET) gene fusion that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options. This indication is approved under accelerated approval based on ORR and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trial.

"In the LIBRETTO-001 trial, selpercatinib demonstrated clinically meaningful and durable responses across a variety of tumor types in patients with RET-driven cancers, including pancreatic, colon and other cancers in need of new treatment options," said Vivek Subbiah, M.D., associate professor of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center and co-investigator for LIBRETTO-001. "These data and FDA approval of the tumor-agnostic indication underscore the importance of routine, comprehensive genomic testing for patients across a wide variety of tumor types."

In addition to the tumor-agnostic approval, the FDA has granted traditional approval for Retevmo in adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with a RET gene fusion, as detected by an FDA-approved test. This FDA action broadens the Retevmo label to include patients with locally advanced disease and converts the May 2020 accelerated approval for NSCLC to a traditional approval.

The labeling for Retevmo contains warnings and precautions for hepatotoxicity (evidence of liver dysfunction), interstitial lung disease (ILD)/pneumonitis, hypertension, QT interval prolongation, hemorrhagic events, hypersensitivity, tumor lysis syndrome, risk of impaired wound healing, hypothyroidism, and embryo-fetal toxicity.

"Since its initial accelerated approval, Retevmo has shifted the treatment paradigm for patients with RET-altered cancers," said David Hyman, M.D., chief medical officer, Loxo@Lilly. "Retevmo is the first and only RET inhibitor to receive both tumor-agnostic accelerated approval and traditional approval in NSCLC, further supporting its ability to deliver meaningful clinical benefit for patients across diverse tumor types."

The two approvals are supported by data from the pivotal LIBRETTO-001 trial, which is the largest clinical trial of patients with RET-driven cancers treated with a RET inhibitor. The multicenter, open-label, multi-cohort study enrolled patients with locally advanced or metastatic RET-driven solid tumors, including NSCLC. Major efficacy outcomes were ORR and DOR, assessed by a blinded independent review committee (BIRC). Prespecified secondary endpoints included central nervous system (CNS) ORR and CNS DOR.

RET Fusion-Positive Solid Tumors
Among the 41 patients in the tumor-agnostic data set, the most common cancers were pancreatic adenocarcinoma (27%), colorectal (24%), salivary (10%), and unknown primary (7%). Thirty-seven patients (90%) received prior systemic therapy (median 2 [range 0 – 9]; 32% received 3 or more). Efficacy results are summarized below:

The activity of Retevmo in patients with CNS metastases was also evaluated. Among the 247 patients with previously treated RET fusion-positive NSCLC, 16 had measurable CNS metastases at baseline as assessed by BIRC. One patient received radiation therapy (RT) to the brain within two months prior to study entry. Responses in intracranial lesions were observed in 87.5% (14 of 16) of patients; 39% of responders had an intracranial DOR of 12 months or greater. Among the 69 patients with treatment-naïve RET fusion-positive NSCLC, five had measurable CNS metastases at baseline as assessed by BIRC. Two patients received RT to the brain within two months prior to study entry. Responses in intracranial lesions were observed in four of these five patients; 38% of responders had an intracranial DOR of 12 months or greater.

"Retevmo's accelerated approval played an important role in providing earlier access for patients who needed new treatment options. We are now pleased to see the conversion from an accelerated approval to a traditional approval," said Andrea Ferris, president and chief executive officer, LUNGevity Foundation. "As a targeted treatment, this traditional approval further reinforces the need for comprehensive biomarker testing for lung cancer patients, with the hope that as many patients as possible can benefit from receiving treatments tailored to their specific tumor mutations."

In the full LIBRETTO-001 safety population (n=796) with advanced solid tumors, the most common adverse reactions (≥25%) were edema, diarrhea, fatigue, dry mouth, hypertension, abdominal pain, constipation, rash, nausea, and headache. The most common Grade 3 or 4 laboratory abnormalities (≥5%) were decreased lymphocytes, increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), decreased sodium, and decreased calcium. For more information, see "IMPORTANT SAFETY INFORMATION FOR RETEVMO® (selpercatinib)" below.

About LIBRETTO-001
The Phase 1/2 LIBRETTO-001 trial is the largest clinical trial of patients with RET-driven cancers treated with a RET inhibitor. The trial, which spans 16 countries and 85 sites, included a dose escalation phase (Phase 1) and a dose expansion phase (Phase 2). The primary objective was to determine ORR by blinded independent review committee (BIRC) and other objectives included DOR, CNS ORR & DOR, safety and PFS.

About Retevmo® (selpercatinib, 40 mg & 80 mg capsules)
Retevmo (selpercatinib, formerly known as LOXO-292) (pronounced ret-tév-mo) is a selective and potent RET kinase inhibitor. Retevmo may affect both tumor cells and healthy cells, which can result in side effects. RET-driver alterations are predominantly mutually exclusive from other oncogenic drivers. Retevmo is a U.S. FDA-approved oral prescription medicine, 120 mg or 160 mg dependent on weight (<50 kg or ≥50 kg, respectively), taken twice daily until disease progression or unacceptable toxicity.

https://www.retevmo.com/

Please see full Prescribing Information for Retevmo.

About Lilly
Lilly unites caring with discovery to create medicines that make life better for people around the world. We've been pioneering life-changing discoveries for nearly 150 years, and today our medicines help more than 47 million people across the globe. Harnessing the power of biotechnology, chemistry and genetic medicine, our scientists are urgently advancing new discoveries to solve some of the world's most significant health challenges, redefining diabetes care, treating obesity and curtailing its most devastating long-term effects, advancing the fight against Alzheimer's disease, providing solutions to some of the most debilitating immune system disorders, and transforming the most difficult-to-treat cancers into manageable diseases. With each step toward a healthier world, we're motivated by one thing: making life better for millions more people. That includes delivering innovative clinical trials that reflect the diversity of our world and working to ensure our medicines are accessible and affordable. To learn more, visit Lilly.com and Lilly.com/newsroom or follow us on Facebook, Instagram, Twitter and LinkedIn. P-LLY

Retevmo® is a registered trademark owned by or licensed to Eli Lilly and Company, its subsidiaries, or affiliates.

PP-SE-US-1166 09/2022

Eli Lilly and Company logo. (PRNewsFoto, Eli Lilly and Company)

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SOURCE Eli Lilly and Company

Eli Lilly wins FDA approval for solid tumor therapy

Sep. 22, 2022 6:58 AM ET

Eli Lilly and Company (LLY)

By: Dulan Lokuwithana, SA News Editor1 Comment

Eli Lilly and Company (NYSE:LLY) announced that the FDA greenlighted its oral lung cancer medication Retevmo under the agency’s accelerated approval for certain adult patients with solid tumors with a specific genetic makeup.

https://seekingalpha.com/news/3885170-lly-stock-gains-after-fda-approval-for-solid-tumor-therapy

https://seekingalpha.com/symbol/LLY

https://www.retevmo.com/

https://www.lilly.com/

Important Facts About RETEVMO® (reh-TEHV-moh). It is also known as selpercatinib. RETEVMO is a prescription medicine that is used to treat certain cancers caused by an abnormal gene, called RET, in: adults with non-small cell lung cancer (NSCLC) that has spread. adults and children 12 years of age and older with advanced medullary thyroid cancer (MTC) or MTC that has spread, who need a medicine that can be taken by mouth or injection. adults and children 12 years of age and older with advanced thyroid cancer or thyroid cancer that has spread, who need a medicine that can be taken by mouth or injection, and who have received radioactive iodine and it did not work or is no longer working. Your doctor will perform a test to make sure that RETEVMO is right for you. It is not known if RETEVMO is safe and effective in children younger than 12 years of age.

TUKYSA® (tucatinib) in Combination with Trastuzumab

Seagen Announces TUKYSA® (tucatinib) in Combination with Trastuzumab Granted Priority Review by FDA for Previously Treated HER2-Positive Metastatic Colorectal Cancer

09/19/2022

- FDA Has Set Action Date of January 19, 2023 -

BOTHELL, Wash.--(BUSINESS WIRE)-- Seagen Inc. (Nasdaq: SGEN) today announced that the U.S. Food and Drug Administration (FDA) has accepted for Priority Review the supplemental New Drug Application (sNDA) seeking accelerated approval for TUKYSA® (tucatinib) in combination with trastuzumab for adult patients with HER2-positive colorectal cancer who have received at least one prior treatment regimen for unresectable or metastatic disease.

The sNDA submission is based on the results of the pivotal phase 2 MOUNTAINEER trial. These data were presented at the European Society for Medical Oncology (ESMO) World Congress on Gastrointestinal Cancer in July 2022.

“There are currently no FDA-approved therapies for metastatic colorectal cancer that specifically target HER2,” said Marjorie Green, M.D., Senior Vice President and Head of Late-Stage Development, Seagen. “The FDA’s prioritization of our application for tucatinib in combination with trastuzumab supports our belief in its significant potential to benefit people with previously treated HER2-positive metastatic colorectal cancer.”

The FDA grants Priority Review to applications for medicines that, if approved, would provide significant improvements in safety or effectiveness of the treatment, diagnosis or prevention of serious diseases. Under the Prescription Drug User Fee Act (PDUFA), the FDA has set a target action date of January 19, 2023. In July 2022, the FDA granted Breakthrough Therapy Designation for tucatinib in combination with trastuzumab for the treatment of adult patients with unresectable or metastatic HER2-positive colorectal cancer who have previously received fluoropyrimidine-, oxaliplatin- and irinotecan-containing chemotherapy based on results from the MOUNTAINEER trial.

In February 2022, Seagen initiated the randomized, global phase 3 MOUNTAINEER-03 clinical trial, which is evaluating tucatinib in combination with trastuzumab and standard chemotherapy versus chemotherapy given with or without cetuximab or bevacizumab in first-line HER2-positive metastatic colorectal cancer. MOUNTAINEER-03 is intended to serve as a confirmatory trial in the U.S. and to support global filings. Merck, known as MSD outside of the U.S. and Canada, is commercializing TUKYSA in regions outside of the U.S., Canada and Europe.

About MOUNTAINEER

MOUNTAINEER is a U.S. and European open-label, multicenter phase 2 clinical trial of tucatinib in combination with trastuzumab or as a single agent that enrolled 117 patients with HER2-positive unresectable or metastatic colorectal cancer following previous standard-of-care therapies. Patients evaluated in MOUNTAINEER had not received prior anti-HER2 therapy. Patients received tucatinib (300 mg) twice per day orally in combination with trastuzumab intravenously (8 mg/kg loading dose, then 6 mg/kg every three weeks thereafter). The primary endpoint of the trial is confirmed objective response rate by RECIST (Response Evaluation Criteria in Solid Tumors) version 1.1 criteria per blinded independent central review. Duration of response, progression-free survival, overall survival and safety and tolerability of the combination regimen are secondary objectives.

About TUKYSA (tucatinib)

TUKYSA is an oral medicine that is a tyrosine kinase inhibitor of the HER2 protein. In vitro (in lab studies), TUKYSA inhibited phosphorylation of HER2 and HER3, resulting in inhibition of downstream MAPK and AKT signaling and cell growth (proliferation), and showed anti-tumor activity in HER2-expressing tumor cells. In vivo (in living organisms), TUKYSA inhibited the growth of HER2-expressing tumors. The combination of TUKYSA and the anti-HER2 antibody trastuzumab showed increased anti-tumor activity in vitro and in vivo compared to either medicine alone.

TUKYSA is approved in 38 countries. It was approved by the U.S. FDA in April 2020 and by the European Medicines Agency and the UK Medicines and Healthcare Products Regulatory Agency in February 2021.

U.S. Indication and Important Safety Information

TUKYSA is indicated in combination with trastuzumab and capecitabine for treatment of adult patients with advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received one or more prior anti-HER2-based regimens in the metastatic setting.

https://www.tukysa.com/

About Seagen

Seagen is a global biotechnology company that discovers, develops and commercializes transformative cancer medicines to make a meaningful difference in people’s lives. Seagen is headquartered in the Seattle, Washington area, and has locations in California, Canada, Switzerland and the European Union. For more information on the company’s marketed products and robust pipeline, visit www.seagen.com and follow @SeagenGlobal on Twitter.

View source version on businesswire.com: https://www.businesswire.com/news/home/20220919005223/en/

Source: Seagen Inc.

Seagen's application seeking nod for colon cancer combo treatment gets FDA priority review

Sep. 19, 2022 9:01 AM ET

Seagen Inc. (SGEN)

By: Anuron Mitra, SA News Editor

Seagen (NASDAQ:SGEN) on Monday said its supplemental new drug application (sNDA) for the accelerated approval of its inhibitor Tukysa in combination with monoclonal antibody trastuzumab to treat colon cancer had been accepted for priority review by the U.S. FDA.
https://seekingalpha.com/news/3883742-seagens-application-seeking-nod-for-colon-cancer-combo-treatment-gets-fda-priority-review
https://seekingalpha.com/symbol/SGEN
https://www.seagen.com/

What is TUKYSA? TUKYSA is a prescription medicine used with the medicines trastuzumab and capecitabine to treat adults with human epidermal growth factor receptor-2 (HER2) positive breast cancer that has spread to other parts of the body such as the brain (metastatic), or that cannot be removed by surgery, and who have received one or more anti-HER2 breast cancer treatments. It is not known if TUKYSA is safe and effective in children.

Veklury® (Remdesivir)

TUKYSA® (tucatinib) in Combination with Trastuzumab

September 16, 2022

CHMP Adopts Positive Opinion to Extend Indication of Veklury® (Remdesivir) for the Treatment of Pediatric Patients with COVID-19

-- If Granted by the European Commission, Veklury Will Become the First and Only Authorized Antiviral Treatment for Pediatric Patients Under 12 Years of Age in the European Union --

FOSTER CITY, Calif.--(BUSINESS WIRE)-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion to extend the indication of Veklury® (remdesivir) for the treatment of pediatric patients (weighing at least 40 kg) who do not require supplemental oxygen and are at increased risk of progressing to severe COVID-19 and pediatric patients (4 weeks of age and older and weighing at least 3 kg) with SARS-CoV-2 with pneumonia who require supplemental oxygen (low- or high-flow oxygen or other non-invasive ventilation at the start of treatment). The European Commission (EC) will review the CHMP recommendation, and if adopted, Veklury will be the only authorized COVID-19 treatment for adolescents at high risk of progressing to severe COVID-19 and pediatric patients with COVID-19 requiring supplemental oxygen.

“As the pandemic persists, there remains a critical need for proven and effective antiviral therapies like Veklury that can treat some of the most vulnerable in our society,” said Merdad Parsey, MD, PhD, Chief Medical Officer, Gilead Sciences. “We are proud of today’s CHMP opinion that represents a positive step toward bridging the treatment gap for children and helping them recover from COVID-19 more quickly.”

This positive opinion was based on results from the ongoing CARAVAN Phase 2/3 study, which demonstrated Veklury was generally well-tolerated among pediatric patients hospitalized with COVID-19, with a high proportion of participants showing clinical improvement and recovery, as well as data from trials in adults. Of the 53 pediatric patients enrolled in the CARAVAN study, no new safety signals were apparent for patients treated with Veklury. Overall, 75% and 85% showed clinical improvement (≥2 point increase on an ordinal scale) at Day 10 and last assessment, respectively, while 60% and 83% were discharged by Day 10 and Day 30, respectively. In the study, 38 patients (72%) experienced adverse events (AEs), with 11 patients (21%) experiencing serious adverse events (SAEs) that were determined not to be study-drug related, including three participant deaths, which were consistent with the patients’ underlying medical conditions prior to study entry or with COVID-19 during hospitalization.

“As the COVID-19 pandemic evolves, it’s important to have effective treatments with well-established safety profiles, including for the vulnerable groups like children to help them recover faster from COVID-19,” said Pablo Rojo, MD, PhD, Pediatric Infectious Diseases Specialist of Hospital 12 de Octubre, Madrid, Spain and Associate Professor of Complutense University, Madrid, Spain. “Therefore, the medical community welcomes this CHMP positive opinion for Veklury in pediatric patients and looks forward to the EC decision.”

In the European Economic Area (EEA), Veklury is the only antiviral indicated for both the treatment of COVID-19 in adult patients who do not require supplemental oxygen and are at increased risk of developing severe COVID-19, as well as adults and adolescents (aged 12 to less than 18 years and weighing at least 40 kg) with pneumonia requiring supplemental oxygen (low- or high-flow oxygen or other non-invasive ventilation at start of treatment).

About Veklury

Veklury (remdesivir) is a nucleotide analog invented by Gilead, building on more than a decade of the company’s antiviral research. Veklury is a foundation for the treatment of hospitalized patients with COVID-19 and is a recommended treatment for reducing disease progression in non-hospitalized patients at high risk of disease progression. Veklury has an established safety profile and minimal known drug interactions in diverse populations. It can help reduce disease progression across a spectrum of disease severity and enable patients to recover faster, freeing up limited hospital resources and saving healthcare systems money.

Veklury directly inhibits viral replication inside of the cell by targeting the SARS-CoV-2 viral RNA polymerase. Based on in vitro analyses, Veklury retains antiviral activity against Omicron subvariants BA.2.12.2, BA.4 and BA.5, which are currently the most common circulating variants. Data continue to confirm that Veklury retains antiviral activity against all Omicron subvariants analyzed to date. Gilead continuously evaluates the activity of Veklury against new SARS-CoV-2 variants of concern as they emerge around the world.

Veklury is approved in more than 50 countries worldwide. To date, Veklury and generic remdesivir have been made available to more than 11 million patients around the world, including more than 7 million people in 127 middle- and low-income countries through Gilead’s voluntary licensing program. These licenses currently remain royalty-free, reflecting Gilead’s existing commitment to enabling broad patient access to remdesivir.

https://www.vekluryhcp.com/

U.S. Indication for Veklury

Veklury® (remdesivir 100 mg for injection) is indicated for the treatment of COVID-19 in adults and pediatric patients (≥28 days old and weighing ≥3 kg) with positive results of SARS-CoV-2 viral testing, who are:

Hospitalized, or
Not hospitalized and have mild-to-moderate COVID-19 and are at high risk for progression to severe COVID-19, including hospitalization or death.

For more information, please see the U.S. full Prescribing Information available at www.gilead.com.

U.S. Important Safety Information for Veklury

https://www.vekluryhcp.com/

View source version on businesswire.com: https://www.businesswire.com/news/home/20220915006144/en/

Source: Gilead Sciences, Inc.

September 15, 2022
WHO Expands Recommendation for Veklury® (Remdesivir) to Patients With Severe Disease in Latest Update to COVID-19 Guideline

Gilead's COVID drug Veklury, cancer therapy Yescarta get EMA panel backing for expanded use

Sep. 16, 2022 7:38 AM ET

Gilead Sciences, Inc. (GILD)

By: Ravikash, SA News Editor1 Comment

A committee of the European Medicines Agency (EMA) recommended the approval of expanded use of Gilead Sciences' (NASDAQ:GILD) Veklury (remdesivir) to treat pediatric patients who do not require supplemental oxygen and are at increased risk of progressing to severe COVID-19.

https://seekingalpha.com/news/3883357-gileads-covid-drug-veklury-cancer-therapy-yescarta-get-ema-panel-backing-for-expanded-use

https://seekingalpha.com/symbol/GILD

https://www.vekluryhcp.com/

https://www.gilead.com/

INDICATION VEKLURY is indicated for the treatment of COVID-19 in adults and pediatric patients (≥28 days old and weighing ≥3 kg) with positive results of SARS-CoV-2 viral testing, who are: Hospitalized, or Not hospitalized, have mild-to-moderate COVID-19, and are at high risk for progression to severe COVID-19, including hospitalization or death.

YESCARTA® (axicabtagene ciloleucel)

September 16, 2022

Kite’s CAR T-cell Therapy Yescarta® First in Europe to Receive Positive CHMP Opinion for Use in Second-line Diffuse Large B-cell Lymphoma and High-grade B-cell Lymphoma

– Positive Opinion Based on Landmark ZUMA-7 Study in Which 41% of Patients Demonstrated Event-Free Survival at Two Years versus 16% for Standard of Care -

SANTA MONICA, Calif.--(BUSINESS WIRE)-- Kite, a Gilead Company (Nasdaq: GILD), today announces that the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion for Yescarta® (axicabtagene ciloleucel) for adult patients with diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma (HGBL) that relapses within 12 months from completion of, or is refractory to, first-line chemoimmunotherapy. If approved, Yescarta will be the first Chimeric Antigen Receptor (CAR) T-cell therapy approved for patients in Europe who do not respond to first-line treatment. Although 60% of newly diagnosed LBCL patients will respond to their initial treatment, 40% will relapse or will not respond and need 2nd line treatment.

“At Kite, we are committed to bringing the curative potential of cell therapy to the world, and changing the way cancer is treated,” said Christi Shaw, CEO, Kite. “Today’s positive CHMP opinion brings us a step closer to utilizing cell therapy earlier in the treatment journey, potentially transforming the standard of care for the most common and aggressive form of non-Hodgkin lymphoma.”

The European Commission will review the CHMP opinion, and a final decision on the marketing authorization is expected in the coming months.

“For people with DLBCL and HGBL who do not respond to first-line treatment or have an early relapse, outcomes are often poor and there are limited curative treatment options for these patients,” said Marie José Kersten, Professor of Hematology at Amsterdam University Medical Centers, Amsterdam. “If approved, axicabtagene ciloleucel may offer a new standard of care for patients with relapsed or refractory DLBCL and HGBL. Importantly, in a randomized trial of axicabtagene ciloleucel versus the current standard of care, quality of life also showed greater improvement in the experimental arm.”

The positive opinion for Yescarta is based on the primary results of the landmark Phase 3 ZUMA-7 study, the largest and longest trial of a CAR T-cell therapy versus standard of care (SOC) in second-line LBCL. Results demonstrated that at a median follow-up of two years, Yescarta-treated patients had a four-fold greater improvement in the primary endpoint of event-free survival (EFS; hazard ratio 0.40; 95% CI: 0.31-0.51, P<0.001) over the current SOC (8.3 months v 2.0 months). Additionally, Yescarta demonstrated a 2.5 fold increase in patients who were alive at two years without disease progression or need for additional cancer treatment vs SOC (41% v 16%). Improvements in EFS with Yescarta were consistent across key patient subgroups, including elderly patients (HR: 0.28 [95% CI: 0.16-0.46]), primary refractory patients (HR: 0.43 [95% CI: 0.32- 0.57]), high-grade B cell lymphoma including double-hit and triple-hit lymphoma patients (HGBL; HR: 0.28 [95% CI: 0.14-0.59]), and double expressor lymphoma patients (HR: 0.42 [95% CI: 0.27-0.67]).

In a separate, secondary analysis of Patient-Reported Outcomes (PROs) published in Blood patients receiving Yescarta and eligible for the PROs portion of the study (n=165) showed statistically significant improvements in Quality of Life (QoL) at Day 100 compared with those who received SOC (n=131), using a pre-specified analysis for three PRO-domains (EORTC QLQ-C30 Physical Functioning, EORTC QLQ-C30 Global Health Status/QOL, and EQ-5D-5L visual analog scale [VAS]). There was also a trend toward faster recovery to baseline QoL in the Yescarta arm versus SOC.

In the ZUMA-7 trial, Yescarta had a manageable safety profile that was consistent with previous studies. Among the 170 Yescarta-treated patients evaluable for safety, Grade ≥3 cytokine release syndrome (CRS) and neurologic events were observed in 6% and 21% of patients, respectively. No Grade 5 CRS or neurologic events occurred. In the SOC arm, 83% of patients had high-grade events, mostly cytopenias (low blood counts).

About ZUMA-7

ZUMA-7 is an ongoing, randomized, open-label, global, multicenter (US, Australia, Canada, Europe, Israel) Phase 3 study of 359 patients at 77 centers, evaluating the safety and efficacy of a single-infusion of Yescarta versus current SOC for second-line therapy (platinum-based salvage combination chemotherapy regimen followed by high-dose chemotherapy and autologous stem cell transplant in those who respond to salvage chemotherapy) in adult patients with relapsed or refractory LBCL within 12 months of first-line therapy. The primary endpoint is event free survival (EFS) as determined by blinded central review, and defined as the time from randomization to the earliest date of disease progression per Lugano Classification, commencement of new lymphoma therapy, or death from any cause. Key secondary endpoints include objective response rate (ORR) and overall survival (OS). Additional secondary endpoints include patient reported outcomes (PROs) and safety.

About Yescarta

Yescarta was first approved in Europe in 2018 and is currently indicated for three types of blood cancer: Diffuse Large B-Cell Lymphoma (DLBCL); Primary Mediastinal Large B-Cell Lymphoma (PMBCL); and Follicular Lymphoma (FL). For the full European Prescribing Information, please visit: https://www.ema.europa.eu/en/medicines/human/EPAR/yescarta

Please see full US Prescribing Information, including BOXED WARNING and Medication Guide.

YESCARTA is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of:

Adult patients with large B-cell lymphoma that is refractory to first-line chemoimmunotherapy or that relapses within 12 months of first-line chemoimmunotherapy.
Adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma, and DLBCL arising from follicular lymphoma.
Limitations of Use: YESCARTA is not indicated for the treatment of patients with primary central nervous system lymphoma.
Adult patients with relapsed or refractory follicular lymphoma (FL) after two or more lines of systemic therapy. This indication is approved under accelerated approval based on the response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trial(s).
https://www.yescarta.com/

About Kite

Kite, a Gilead Company, is a global biopharmaceutical company based in Santa Monica, California, with manufacturing operations in North America and Europe. Kite’s singular focus is cell therapy to treat and potentially cure cancer. As the cell therapy leader, Kite has more approved CAR T indications to help more patients than any other company. For more information on Kite, please visit www.kitepharma.com. Follow Kite on social media on Twitter (@KitePharma) and LinkedIn.

About Gilead Sciences

Gilead Sciences, Inc. is a biopharmaceutical company that has pursued and achieved breakthroughs in medicine for more than three decades, with the goal of creating a healthier world for all people. The company is committed to advancing innovative medicines to prevent and treat life-threatening diseases, including HIV, viral hepatitis and cancer. Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, California.

View source version on businesswire.com: https://www.businesswire.com/news/home/20220916005209/en/

Source: Gilead Sciences, Inc.

Gilead's COVID drug Veklury, cancer therapy Yescarta get EMA panel backing for expanded use

Sep. 16, 2022 7:38 AM ET

Gilead Sciences, Inc. (GILD)

By: Ravikash, SA News Editor1 Comment

https://seekingalpha.com/news/3883357-gileads-covid-drug-veklury-cancer-therapy-yescarta-get-ema-panel-backing-for-expanded-use

https://seekingalpha.com/symbol/GILD

https://www.yescarta.com/

APPROVED USE YESCARTA is a prescription medicine used to treat two types of non-Hodgkin lymphoma: large B-cell lymphoma when your first treatment did not work or your cancer returned within a year of first treatment, OR when at least two kinds of treatment have failed to control your cancer. follicular lymphoma when at least two kinds of treatment have failed to control your cancer. YESCARTA is different than other cancer medicines because it is made from your own white blood cells, which have been modified to recognize and attack your lymphoma cells.

OPDIVO® (nivolumab)

YESCARTA® (axicabtagene ciloleucel)

Bristol Myers Squibb Announces Adjuvant Treatment with Opdivo (nivolumab) Demonstrated Statistically Significant and Clinically Meaningful Improvement in Recurrence-Free Survival (RFS) in Patients with Stage IIB/C Melanoma in the CheckMate -76K Trial

09/15/2022CATEGORY:

Corporate/Financial News

Positive results from CheckMate -76K reinforce the potential benefit of Opdivo in earlier stages of melanoma

PRINCETON, N.J.--(BUSINESS WIRE)-- Bristol Myers Squibb (NYSE: BMY) today announced that the Phase 3 CheckMate -76K trial evaluating Opdivo (nivolumab) as a single agent in the adjuvant settingin patients with completely resected stage IIB/C melanoma met its primary endpoint and demonstrated a statistically significant and clinically meaningful benefit in recurrence-free survival (RFS) versus placebo at a pre-specified interim analysis. No new safety signals were observed at the time of the analysis.

CheckMate -76K is part of BMS’ development program studying Opdivo and Opdivo-based combinations in earlier stages of cancer, which currently spans seven tumor types.

“Stage IIB/C melanoma patients are at high risk of disease recurrence, with approximately one third of stage IIB and half of stage IIC patients experiencing recurrence within five years after surgery. The results of the CheckMate -76K study represent a significant advancement for patients with stage IIB/C melanoma and an extension of our legacy in the treatment of melanoma,” said Gina Fusaro, PhD, development program lead, melanoma, Bristol Myers Squibb. “Recurrence represents a life-altering event for people living with cancer. Treating with Opdivo in earlier stages of cancer, when the immune system may be more responsive, has the potential to help prevent recurrence – a critical goal of improving patient outcomes.”

The company will complete a full evaluation of the CheckMate -76K data and looks forward to sharing the results at an upcoming medical conference, as well as with health authorities. Bristol Myers Squibb thanks the patients and investigators who were involved in the CheckMate -76K clinical trial.

About CheckMate -76K

CheckMate -76K is a randomized Phase 3, double-blind study evaluating adjuvant Opdivo (nivolumab) 480 mg Q4W for up to 12 months versus placebo in patients with completely resected stage IIB/C melanoma.

The primary endpoint of the trial is recurrence-free survival (RFS). Secondary endpoints of the trial include overall survival (OS), distant metastases-free survival (DMFS), progression-free survival on next-line therapy (PFS2), and safety endpoints.

About Melanoma

Melanoma is a form of skin cancer characterized by the uncontrolled growth of pigment-producing cells (melanocytes) located in the skin. Metastatic melanoma is the deadliest form of the disease and occurs when cancer spreads beyond the surface of the skin to other organs. The incidence of melanoma has been increasing steadily for the last 30 years. In the United States, 99,780 new diagnoses of melanoma and about 7,650 related deaths are estimated for 2022. Globally, the World Health Organization estimates that by 2035, melanoma incidence will reach 424,102, with 94,308 related deaths. Melanomas can be mostly treatable when caught in very early stages; however, survival rates can decrease as the disease progresses.

Bristol Myers Squibb: Creating a Better Future for People with Cancer

Bristol Myers Squibb is inspired by a single vision — transforming patients’ lives through science. The goal of the company’s cancer research is to deliver medicines that offer each patient a better, healthier life and to make cure a possibility. Building on a legacy across a broad range of cancers that have changed survival expectations for many, Bristol Myers Squibb researchers are exploring new frontiers in personalized medicine, and through innovative digital platforms, are turning data into insights that sharpen their focus. Deep scientific expertise, cutting-edge capabilities and discovery platforms enable the company to look at cancer from every angle. Cancer can have a relentless grasp on many parts of a patient’s life, and Bristol Myers Squibb is committed to taking actions to address all aspects of care, from diagnosis to survivorship. Because as a leader in cancer care, Bristol Myers Squibb is working to empower all people with cancer to have a better future.

About Opdivo

Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body’s own immune system to help restore anti-tumor immune response. By harnessing the body’s own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers.

Opdivo’s leading global development program is based on Bristol Myers Squibb’s scientific expertise in the field of Immuno-Oncology, and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical development program has treated more than 35,000 patients. The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression.

In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 65 countries, including the United States, the European Union, Japan and China. In October 2015, the Company’s Opdivo and Yervoy combination regimen was the first Immuno-Oncology combination to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 50 countries, including the United States and the European Union.

OPDIVO U.S. INDICATIONS

OPDIVO® (nivolumab), as a single agent, is indicated for the treatment of adult patients with unresectable or metastatic melanoma.

OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of adult patients with unresectable or metastatic melanoma.

OPDIVO® (nivolumab) is indicated for the adjuvant treatment of adult patients with melanoma with involvement of lymph nodes or metastatic disease who have undergone complete resection.

OPDIVO® (nivolumab), in combination with platinum-doublet chemotherapy, is indicated as neoadjuvant treatment of adult patients with resectable (tumors ≥4 cm or node positive) non-small cell lung cancer (NSCLC).

OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 (≥1%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.

OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab) and 2 cycles of platinum-doublet chemotherapy, is indicated for the first-line treatment of adult patients with metastatic or recurrent non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

OPDIVO® (nivolumab) is indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving OPDIVO.

OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with unresectable malignant pleural mesothelioma (MPM).

OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with intermediate or poor risk advanced renal cell carcinoma (RCC).

OPDIVO® (nivolumab), in combination with cabozantinib, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC).

OPDIVO® (nivolumab) is indicated for the treatment of adult patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy.

OPDIVO® (nivolumab) is indicated for the treatment of adult patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin or after 3 or more lines of systemic therapy that includes autologous HSCT. This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

OPDIVO® (nivolumab) is indicated for the treatment of adult patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after platinum-based therapy.

OPDIVO® (nivolumab) is indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

OPDIVO® (nivolumab), as a single agent, is indicated for the adjuvant treatment of adult patients with urothelial carcinoma (UC) who are at high risk of recurrence after undergoing radical resection of UC.

OPDIVO® (nivolumab), as a single agent, is indicated for the treatment of adult and pediatric (12 years and older) patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of adults and pediatric patients 12 years and older with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of adult patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

OPDIVO® (nivolumab) is indicated for the treatment of adult patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine- and platinum-based chemotherapy.

OPDIVO® (nivolumab) is indicated for the adjuvant treatment of completely resected esophageal or gastroesophageal junction cancer with residual pathologic disease in adult patients who have received neoadjuvant chemoradiotherapy (CRT).

OPDIVO® (nivolumab), in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adult patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC).

OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC).

OPDIVO® (nivolumab), in combination with fluoropyrimidine- and platinum- containing chemotherapy, is indicated for the treatment of adult patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma.

https://www.opdivo.com/

Please see US Full Prescribing Information for OPDIVO and YERVOY.

About Bristol Myers Squibb

Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube, Facebook and Instagram.

Source: Bristol Myers Squibb

Bristol Myers Opdivo shows survival benefit as adjuvant therapy for skin cancer in trial

Sep. 15, 2022 8:10 AM ET

Bristol-Myers Squibb Company (BMY)

By: Ravikash, SA News Editor

Bristol Myers Squibb (NYSE:BMY) said Opdivo as an adjuvant therapy met the main goal of a phase 3 trial called CheckMate -76K in patients with completely resected stage IIB/C melanoma, a type of skin cancer.
https://seekingalpha.com/news/3882972-bristol-myers-opdivo-shows-survival-benefit-as-adjuvant-therapy-for-skin-cancer-in-trial
https://seekingalpha.com/symbol/BMY
https://www.opdivo.com/
https://www.bms.com/

OPDIVO® Immunotherapy: Giving People a Choice and a Chance Against Their Cancer BACK Non-Small Cell Lung Cancer (NSCLC) OPDIVO + YERVOY for certain adults with newly diagnosed advanced NSCLC that test positive for PD-L1 OPDIVO + YERVOY, with chemotherapy, for adults with newly diagnosed advanced NSCLC OPDIVO, with chemotherapy, for adults with early-stage NSCLC before surgery OPDIVO for adults who have had prior treatments for NSCLC Choose your condition: Non-Small Cell Lung Cancer (NSCLC) Advanced Kidney Cancer Advanced Liver Cancer Colorectal Cancer (MSI-H/dMMR) Gastric (Stomach), or Gastroesophageal Junction, or Esophageal Cancers Melanoma Head and Neck Squamous Cell Cancer Bladder or Urinary Tract Cancer (Urothelial) Classical Hodgkin Lymphoma Malignant Pleural Mesothelioma

KEYTRUDA® (pembrolizumab)

YESCARTA® (axicabtagene ciloleucel)

PADCEV® (enfortumab vedotin-ejfv) With KEYTRUDA® (pembrolizumab)

Health Canada Approves KEYTRUDA® (pembrolizumab) as Adjuvant Treatment for Adults and Children with Stage IIB or IIC Melanoma Following Complete Resection

Sep. 13, 2022 7:05 AM ETMerck & Co., Inc. (MRK)

Approval is based on the Phase 3 KEYNOTE-716 Trial

Melanoma is the most serious of all skin cancers, with over 5,000 Canadians diagnosed each year.1,2

KIRKLAND, QC, Sept. 13, 2022 /CNW/ - Merck (MRK), known as MSD outside the United States and Canada, announced that Health Canada has granted approval for KEYTRUDA® (pembrolizumab), Merck's anti-PD-1 therapy, for the adjuvant treatment of adult and pediatric (12 years and older) patients with stage IIB or IIC melanoma following complete resection.3 This approval is based on the results from the Phase 3 KEYNOTE-716 trial, which demonstrated a statistically significant improvement in recurrence-free survival (RFS).3

In 2022, an estimated 9,000 Canadians will be diagnosed with melanoma,4 a form of cancer that takes place when melanocytes, the cells responsible for melanin production, start to grow uncontrollably and develop into a tumour.5 Although it is the least common of all skin cancers, melanoma is the most serious type and early diagnosis and treatment are critical.1,5

"We welcome the news of a new treatment option for Canadians living with this disease as the incidence of melanoma continues to rise across the country,"6,8 said Kathy Barnard, Founder/President of Save Your Skin Foundation. "Having options available right after surgery can help take action against a disease that moves quickly if not caught."

"Melanoma can affect anyone, including children, for whom, although rare, this is the most common amongst pediatric skin cancer types,"7 said Falyn Katz, Executive Director, Melanoma Canada. "Having options available, like this one, can help to make a difference for Canadians facing this particular type of skin cancer, helping them navigate the disease."

About KEYNOTE-716 Trial
Health Canada's approval is based on findings from KEYNOTE-716, a multicenter, randomized, double-blind, placebo-controlled clinical trial in patients (n=976) with completely resected stage IIB or IIC melanoma.3 Only patients that had not been previously treated for melanoma beyond complete surgical resection for their melanoma prior to study entry were included in the trial.3 Patients were randomized to KEYTRUDA® 200 mg or the pediatric (≥12 years old) dose of KEYTRUDA® 2 mg/kg intravenously (up to a maximum of 200 mg) every three weeks (n=487) or placebo (n=489) for up to one year until disease recurrence or unacceptable toxicity.3 The primary efficacy outcome was investigator-assessed recurrence-free survival (RFS). RFS was defined as the time between the date of randomization and the date of first recurrence (local, regional, or distant metastasis) or death, whichever occurs first.3

The results of KEYNOTE-716 demonstrated a statistically significant improvement in RFS for patients randomized to receive KEYTRUDA® compared with patients randomized to placebo at the first pre-specified interim analysis.3 At the time of median follow-up (14.3 months), 11% (n=54/487) of patients who received KEYTRUDA® had a recurrence or died compared to 17% (n=82/489) of patients who received placebo.

In the study, the safety profile of KEYTRUDA® was consistent with previously reported studies in patients with solid tumors. The most common treatment-related adverse events (reported in at least 15% of patients) were pruritis, fatigue, diarrhea, and rash. KEYTRUDA® was discontinued for treatment-related adverse events in 15% of patients in KEYNOTE-716. Refer to the product monograph for complete information.3

"This approval is important for people living with melanoma and for all of us at Merck," said Marwan Akar, President, and Managing Director, Merck Canada. "With this new indication, KEYTRUDA® is the first checkpoint inhibitor approved in Canada in the adjuvant space in Stage IIB or IIC melanoma, meaning it can be considered for patients earlier in their journey. We are proud to continue to pursue our passion to save and improve lives as well as reinforce our commitment to finding innovative and effective options for more patients with melanoma."

About KEYTRUDA®
KEYTRUDA® is an anti-PD-1 therapy that works by helping increase the ability of the body's immune system to help detect and fight tumour cells.3 KEYTRUDA® is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumour cells and healthy cells.3

KEYTRUDA® was first approved in Canada in 2015 and currently has indications in several disease areas, including advanced renal cell carcinoma, bladder cancer, non-small cell lung carcinoma, primary mediastinal B-cell lymphoma, classical Hodgkin lymphoma, colorectal cancer, endometrial carcinoma, esophageal cancer, triple-negative breast cancer, melanoma, and head and neck squamous cell carcinoma.3

https://www.keytruda.com/

About Merck
At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information about our operations in Canada, visit www.merck.ca and connect with us on YouTube and Twitter @MerckCanada.

SOURCE Merck Canada

Merck's Keytruda gets approval in Canada for certain skin cancer patients following surgery

Sep. 13, 2022 8:10 AM ET

Merck & Co., Inc. (MRK)

By: Ravikash, SA News Editor2 Comments

Health Canada approved Merck's (NYSE:MRK) blockbuster drug Keytruda (pembrolizumab) as an adjuvant therapy for patients 12 years and older with stage IIB or IIC melanoma following complete resection.
https://seekingalpha.com/news/3882274-mercks-keytruda-gets-approval-in-canada-for-certain-skin-cancer-patients-following-surgery
https://seekingalpha.com/symbol/MRK
https://www.keytruda.com/
https://www.merck.com/

PADCEV® (enfortumab vedotin-ejfv) With KEYTRUDA® (pembrolizumab)

Seagen, Astellas and Merck Announce Results of Clinical Trial Investigating PADCEV® (enfortumab vedotin-ejfv) With KEYTRUDA® (pembrolizumab) and PADCEV as Monotherapy in First-Line Advanced Urothelial Cancer

September 12, 2022 8:55 am ET

Results demonstrated a 64.5% confirmed objective response rate in patients treated with investigational combination of enfortumab vedotin and pembrolizumab

Data highlighted in late-breaking presentation at the European Society for Medical Oncology Congress 2022

BOTHELL, W.A., TOKYO and RAHWAY, N.J., Sept.12, 2022 – Seagen Inc. (Nasdaq:SGEN), Astellas Pharma Inc. (TSE:4503, President and CEO: Kenji Yasukawa, Ph.D., “Astellas”) and Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced results from the Phase 1b/2 EV-103 clinical trial (also known as KEYNOTE-869) Cohort K investigating PADCEV® (enfortumab vedotin-ejfv) in combination with Merck’s anti-PD-1 therapy KEYTRUDA® (pembrolizumab) and PADCEV alone as first-line treatment in patients with unresectable locally advanced or metastatic urothelial cancer (la/mUC) who are ineligible to receive cisplatin-based chemotherapy. The findings were presented today at the European Society for Medical Oncology (ESMO) Congress as part of a late-breaking abstract presentation (Abstract #LBA73).

In patients treated with enfortumab vedotin and pembrolizumab (n=76), results demonstrated a 64.5% confirmed objective response rate (ORR) (95% CI, 52.7-75.1) per RECIST v1.1 by blinded independent central review (BICR), the primary endpoint of Cohort K, with 10.5% of patients experiencing a complete response and 53.9% of patients experiencing a partial response. The median duration of response (DOR) per BICR was not reached (95% CI, 10.25-NR). All-grade treatment-related adverse events (TRAEs) of special interest for enfortumab vedotin in combination with pembrolizumab were skin reactions (67.1%), peripheral neuropathy (60.5%), ocular disorders (dry eye, blurred vision and corneal disorders) (26.3%), hyperglycemia (14.5%) and infusion-related reactions (3.9%). Pembrolizumab adverse events of special interest were consistent with previously observed safety data from monotherapy with the exception of severe skin reactions. Overall, the results were generally consistent with previously reported efficacy and safety results of the EV-103/KEYNOTE-869 dose-escalation cohort and expansion Cohort A.

Please see Important Safety Information at the end of this press release for both drugs, including BOXED WARNING for enfortumab vedotin and immune mediated adverse reactions for pembrolizumab.

Cohort K also included a monotherapy arm in which patients were treated with enfortumab vedotin alone (n=73), though this study was not designed to support a formal comparison between the two arms. Results showed a 45.2% confirmed ORR (95% CI, 33.5-57.3) per RECIST v1.1 by BICR, with 4.1% of patients experiencing a complete response and 41.1% of patients experiencing a partial response. The median DOR was 13.2 months (95% CI, 6.14-15.97) per RECIST v1.1 by BICR. All-grade TRAEs of special interest for enfortumab vedotin were peripheral neuropathy (54.8%), skin reactions (45.2%), ocular disorders (dry eye, blurred vision and corneal disorders) (28.8%), hyperglycemia (11.0%) and infusion-related reactions (5.5%).

Additional secondary endpoints in the EV-103 Cohort K trial included progression-free survival (PFS) and overall survival (OS). Among patients treated with enfortumab vedotin and pembrolizumab, median PFS was not reached (95% CI, 8.31-NR). Median OS was 22.3 months (95% CI, 19.09-NR). Among patients treated with enfortumab vedotin, median PFS was 8.0 months (95% CI, 6.05-10.35), and median OS was 21.7 months (95% CI, 15.21-NR).

The TRAEs of any grade that occurred in more than 20% of patients treated with enfortumab vedotin alone or in combination with pembrolizumab were fatigue, peripheral sensory neuropathy, alopecia, rash maculo-papular, pruritus, dysgeusia, weight decreased, diarrhea, decreased appetite, nausea and dry eye.

“Results from EV-103/KEYNOTE-869 Cohort K support the ongoing investigation of enfortumab vedotin and pembrolizumab in cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer who are in need of treatment options, and this combination may be an important therapeutic option for these patients,” said Dr. Jonathan E. Rosenberg, M.D., chief, genitourinary medical oncology service, division of solid tumor oncology and Enno W. Ercklentz chair, Memorial Sloan Kettering Cancer Center and EV-103/KEYNOTE-869 Cohort K primary investigator. Dr. Rosenberg has consulting relationships with Seagen, Astellas and Merck.

“Nearly 65% of patients who were treated with enfortumab vedotin and pembrolizumab responded to this combination, with almost 11% showing no detectable cancer following treatment. These study results represent an encouraging finding for people with advanced urothelial cancer who are not eligible for cisplatin treatment,” said Margorie Green, senior vice president and head of late stage development, Seagen.

“We’re encouraged by these positive findings from the combination of enfortumab vedotin and pembrolizumab in people with advanced urothelial cancer who historically have had limited treatment options in the first-line setting, and we intend to discuss these results with regulatory authorities,” said Ahsan Arozullah, M.D., M.P.H., senior vice president and head of development therapeutic areas, Astellas.

“We’re pleased that this combination provided a meaningful benefit to this group of advanced bladder cancer patients in this study, and we will continue to investigate enfortumab vedotin plus pembrolizumab through our collaboration,” said Eliav Barr, M.D., senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories.

In February 2020, the U.S. Food and Drug Administration granted Breakthrough Therapy Designation for enfortumab vedotin in combination with pembrolizumab for patients with unresectable la/mUC who are ineligible to receive cisplatin-based chemotherapy in the first-line setting. The designation is based on results from the dose-escalation cohort and expansion Cohort A of the phase 1b/2 trial, EV-103/KEYNOTE-869 (NCT03288545), evaluating patients with la/mUC who are ineligible to receive cisplatin-based chemotherapy treated in the first-line setting with enfortumab vedotin in combination with pembrolizumab.

Seagen, Astellas and Merck are further investigating enfortumab vedotin plus pembrolizumab in Phase 3 studies, including EV-302/KEYNOTE-A39 (NCT04223856), which is intended to confirm these results for the investigational treatment combination in previously untreated la/mUC, and in muscle-invasive bladder cancer in EV-304/KEYNOTE-B15 (NCT04700124) and EV-303/KEYNOTE-905 (NCT03924895).

About the EV-103/KEYNOTE-869 trial (Cohort K)

The EV-103/KEYNOTE-869 trial (NCT03288545) is an ongoing, multi-cohort, open-label, multicenter Phase 1b/2 trial of enfortumab vedotin alone or in combination with pembrolizumab and/or chemotherapy in first- or second-line settings in patients with la/mUC and in patients with muscle-invasive bladder cancer.

Cohort K of the EV-103/KEYNOTE-869 trial is a randomized 1:1 cohort investigating enfortumab vedotin alone (n=73) or in combination with pembrolizumab (n=76) in adult patients with unresectable la/mUC who are ineligible for cisplatin-based chemotherapy and have received no prior treatment for la/mUC. The enfortumab vedotin monotherapy study arm is intended to characterize the activity of enfortumab vedotin alone in this patient population. The key outcome measure of EV-103/KEYNOTE-869 Cohort K is ORR per BICR using RECIST 1.1. Secondary endpoints include ORR per investigator assessment; DOR, disease control rate and progression-free survival per BICR and investigator assessment; overall survival; and assessment of safety.

About PADCEV

PADCEV (enfortumab vedotin-ejfv) is a first-in-class antibody-drug conjugate (ADC) that is directed against Nectin-4, a protein located on the surface of cells and highly expressed in bladder cancer. Nonclinical data suggest the anticancer activity of PADCEV is due to its binding to Nectin-4 expressing cells followed by the internalization and release of the anti-tumor agent monomethyl auristatin E (MMAE) into the cell, which result in the cell not reproducing (cell cycle arrest) and in programmed cell death (apoptosis).

PADCEV (enfortumab vedotin-ejfv) U.S. Indication & Important Safety Information

Indication

PADCEV® is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer (mUC) who:

have previously received a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor and platinum-containing chemotherapy, or
are ineligible for cisplatin-containing chemotherapy and have previously received one or more prior lines of therapy.
https://www.padcev.com/
For more information, please see the full Prescribing Information including BOXED WARNING for PADCEV here.

About the Seagen, Astellas and Merck collaboration

Seagen and Astellas entered a clinical collaboration agreement with Merck to evaluate the combination of Seagen’s and Astellas’ PADCEV® (enfortumab vedotin-ejfv) and Merck’s KEYTRUDA® (pembrolizumab) in patients with previously untreated metastatic urothelial cancer. KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Rahway, N.J., USA.

About Seagen

Seagen Inc. is a global biotechnology company that discovers, develops and commercializes transformative cancer medicines to make a meaningful difference in people’s lives. Seagen is headquartered in the Seattle, Washington area, and has locations in California, Canada, Switzerland and the European Union. For more information on the company’s marketed products and robust pipeline, visit www.seagen.com and follow @SeagenGlobal on Twitter.

About Astellas

Astellas Pharma Inc. is a pharmaceutical company conducting business in more than 70 countries around the world. We are promoting the Focus Area Approach that is designed to identify opportunities for the continuous creation of new drugs to address diseases with high unmet medical needs by focusing on Biology and Modality. Furthermore, we are also looking beyond our foundational Rx focus to create Rx+® healthcare solutions that combine our expertise and knowledge with cutting-edge technology in different fields of external partners. Through these efforts, Astellas stands on the forefront of healthcare change to turn innovative science into value for patients. For more information, please visit our website at https://www.astellas.com/en.

Merck’s focus on cancer

Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck, the potential to bring new hope to people with cancer drives our purpose and supporting accessibility to our cancer medicines is our commitment. As part of our focus on cancer, Merck is committed to exploring the potential of immuno-oncology with one of the largest development programs in the industry across more than 30 tumor types. We also continue to strengthen our portfolio through strategic acquisitions and are prioritizing the development of several promising oncology candidates with the potential to improve the treatment of advanced cancers. For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.

About Merck

At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.merck.com and connect with us on Twitter, Facebook, Instagram, YouTube and LinkedIn.

Seagen, Astellas and Merck Announce Results of Clinical Trial Investigating PADCEV® (enfortumab vedotin-ejfv) with KEYTRUDA® (pembrolizumab) and PADCEV as Monotherapy in First-Line Advanced Urothelial Cancer

09/12/2022

– Results demonstrated a 64.5% confirmed objective response rate in patients treated with investigational combination of enfortumab vedotin and pembrolizumab –

– Data highlighted in late-breaking presentation at the European Society for Medical Oncology (ESMO) Congress 2022 –

BOTHELL, Wash. & TOKYO & RAHWAY, N.J.--(BUSINESS WIRE)-- Seagen Inc. (Nasdaq:SGEN), Astellas Pharma Inc. (TSE:4503, President and CEO: Kenji Yasukawa, Ph.D., “Astellas”) and Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced results from the phase 1b/2 EV-103 clinical trial (also known as KEYNOTE-869) Cohort K investigating PADCEV® (enfortumab vedotin-ejfv) in combination with Merck’s anti-PD-1 therapy KEYTRUDA® (pembrolizumab) and PADCEV alone as first-line treatment in patients with unresectable locally advanced or metastatic urothelial cancer (la/mUC) who are ineligible to receive cisplatin-based chemotherapy. The findings were presented today at the European Society for Medical Oncology (ESMO) Congress as part of a late-breaking abstract presentation (Abstract #LBA73).

https://investor.seagen.com/press-releases/news-details/2022/Seagen-Astellas-and-Merck-Announce-Results-of-Clinical-Trial-Investigating-PADCEV-enfortumab-vedotin-ejfv-with-KEYTRUDA-pembrolizumab-and-PADCEV-as-Monotherapy-in-First-Line-Advanced-Urothelial-Cancer/default.aspx

Astellas/Seagen, Merck Padcev/Keytruda combo shows promise in urothelial cancer in trial

Sep. 12, 2022 9:51 AM ET

Merck & Co., Inc. (MRK), SGEN, ALPMY, ALPMF

By: Ravikash, SA News Editor

Astellas Pharma (OTCPK:ALPMF) (OTCPK:ALPMY), Seagen (NASDAQ:SGEN) and Merck (NYSE:MRK) said Padcev and Keytruda showed a 64.5% confirmed objective response rate (ORR) in patients with a type of urothelial cancer.

https://seekingalpha.com/news/3882015-astellasseagen-merck-padcevkeytruda-combo-shows-promise-in-urothelial-cancer-in-trial

https://seekingalpha.com/symbol/ALPMF

https://seekingalpha.com/symbol/ALPMY

https://seekingalpha.com/symbol/SGEN

https://seekingalpha.com/symbol/MRK

https://www.padcev.com/

https://www.keytruda.com/

WHAT IS PADCEV®? PADCEV is a prescription medicine used to treat adults with bladder cancer and cancers of the urinary tract (renal pelvis, ureter or urethra) that has spread or cannot be removed by surgery. PADCEV may be used if you: • have received an immunotherapy medicine and chemotherapy that contains platinum, or • you are not able to receive a chemotherapy that contains the medicine cisplatin and you have received one or more prior therapy. It is not known if PADCEV is safe and effective in children.

RUBRACA® (rucaparib) tablets

PADCEV® (enfortumab vedotin-ejfv) With KEYTRUDA® (pembrolizumab)

ENHERTU® (fam-trastuzumab deruxtecan-nxki) for injection

Clovis Oncology’s Rubraca® (Rucaparib) As First-Line Maintenance Treatment Improves Progression-Free Survival In Women With Advanced Ovarian Cancer Across Disease Risk Subgroups

September 11, 2022 Download this Press ReleasePDF Format (opens in new window)

Subgroup analysis from the Phase 3 ATHENA trial evaluating Rubraca monotherapy versus placebo (ATHENA-MONO) presented in a Mini Oral session at the ESMO Congress 2022
Results reinforce potential of Rubraca as a first-line maintenance treatment option in a broad population of patients with ovarian cancer irrespective of molecular characteristics, with or without high risk factors for progression

BOULDER, Colo.--(BUSINESS WIRE)-- Clovis Oncology, Inc. (NASDAQ: CLVS), today announced results from a subgroup analysis of data from the monotherapy comparison of the randomized, Phase 3 ATHENA (GOG-3020/ENGOT-ov45) trial (ATHENA-MONO). These data showed that Rubraca as first-line maintenance treatment improved progression-free survival (PFS) versus placebo across disease risk subgroups including surgical outcome, response to first-line chemotherapy, and additional analyses in other subgroups. The data were presented by Rebecca S. Kristeleit, MD, PhD, of Guy’s and St. Thomas’ NHS Foundation Trust in London and lead ENGOT/NCRI National Cancer Research Institute (https://www.ncri.org.uk/) investigator of the ATHENA trial as a Mini Oral abstract at the European Society of Medical Oncology (ESMO) Congress 2022 in Paris.

“These additional results from the ATHENA-MONO analysis of the Phase 3 ATHENA trial demonstrate that rucaparib should be considered a new first-line maintenance treatment option for women with advanced ovarian cancer,” Dr. Kristeleit said. “In this analysis, rucaparib prolonged progression-free survival for patients with or without high risk factors for progression, irrespective of molecular characteristics, adding to our understanding of the efficacy of rucaparib in the broadest population of patients assessed in a clinical trial for first-line PARP inhibitor monotherapy.”

ATHENA is a double-blind, placebo-controlled, Phase 3 trial of Rubraca in first-line ovarian cancer maintenance treatment. It has two parts which are statistically independent. The results presented at ESMO are from the ATHENA-MONO part (Rubraca versus placebo), with results from the ATHENA-COMBO part (Rubraca plus nivolumab versus Rubraca) expected in Q1 2023.

“As further demonstrated by the additional data presented at ESMO, the ATHENO-MONO analysis continues to reinforce the potential of Rubraca as a first-line maintenance therapy for women with advanced ovarian cancer,” said Patrick J. Mahaffy, President and CEO of Clovis Oncology. “We remain grateful to the patients who participated in the trial and for the support of the clinical community familiar with these results.”

ATHENA-MONO enrolled 538 women with high-grade ovarian, fallopian tube, or primary peritoneal cancer. The primary efficacy analysis evaluated two prospectively defined molecular subgroups in a step-down manner: 1) homologous recombination deficiency (HRD)-positive (inclusive of BRCAm tumors and BRCAwt/LOH high tumors), and 2) all patients randomized (overall intent-to-treat population [ITT]) in ATHENA-MONO. The following exploratory subgroup analyses are included in the ESMO presentation:

PFS by Surgical Outcome

Patients who received Rubraca as maintenance therapy showed benefit regardless of surgical outcome, whether there was complete resection (R0) during cytoreductive surgery or not.

In HRD-positive patients:

Patients who had a complete resection following cytoreductive surgery (R0):
- Rubraca (n=107), median PFS not yet reached (NR); placebo (n=33), median PFS of 22.1 months
- Hazard ratio of 0.52 (95% [Confidence Interval] CI: 0.30-0.92)
Patients who did not have a complete resection following cytoreductive surgery (non-R0):
- Rubraca (n=78), median PFS of 20.3 months; placebo (n=16), median PFS of 9.1 months
- Hazard ratio of 0.29 (95% CI: 0.15-0.56)

Among the ITT population:

Patients who had a complete resection following cytoreductive surgery (R0):
- Rubraca (n=263), median PFS of 25.1 months; placebo (n=73), median PFS of 12.0 months
- Hazard ratio of 0.60 (95% CI: 0.43-0.84)
Patients who did not have a complete resection following cytoreductive surgery (non-R0):
- Rubraca (n=164), median PFS of 13.9 months; placebo (n=38), median PFS of 6.4 months
- Hazard ratio of 0.41 (95% CI: 0.27-0.62)

PFS by First-Line Chemotherapy Response

Similarly, patients treated with Rubraca as maintenance therapy showed benefit among all subgroups when evaluated against response per RECIST v1.1 at any time during first-line chemotherapy.

Among HRD-positive patients:

Patients who demonstrated a partial response to first-line chemotherapy:
- Rubraca (n=33), median PFS of 14.8 months; placebo (n=9), median PFS of 9.1 months
- Hazard ratio of 0.43 (95% CI: 0.18-1.02)
Patients who demonstrated a complete response to first-line chemotherapy:
- Rubraca (n=38), median PFS of 25.8 months; placebo (n=4), median PFS NR
- Hazard ratio of 0.41 (95% CI: 0.10-1.63)

Among the ITT population:

Patients who demonstrated a partial response to first-line chemotherapy:
- Rubraca (n=76), median PFS of 12.2 months; placebo (n=22), median PFS of 6.4 months
- Hazard ratio of 0.37 (95% CI: 0.21-0.65)
Patients who demonstrated a complete response to first-line chemotherapy:
- Rubraca (n=73), median PFS of 15.6 months; placebo (n=11), median PFS of 6.4 months
- Hazard ratio of 0.48 (95% CI: 0.23-1.03)

Additional Analyses in the ITT Population by Subgroup

Additional analyses in other subgroups based on baseline clinical characteristics, including FIGO stage, timing of surgery, and CA-125 levels, also demonstrated that patients treated with Rubraca experienced a progression-free survival benefit compared to those treated with placebo. Safety was similar between subgroups analyzed.

Dr. Kristeleit’s presentation, as well as other company-sponsored Rubraca data presented at ESMO, can be viewed at the time of presentation at https://www.clovisoncology.com/pipeline/scientific-presentations/.

Rubraca is not currently approved in the first-line ovarian cancer maintenance setting.

About Rubraca (rucaparib)

Rucaparib is an oral, small molecule inhibitor of PARP1, PARP2 and PARP3 being developed in multiple tumor types, including ovarian and metastatic castration-resistant prostate cancers, as monotherapy, and in combination with other anti-cancer agents. Exploratory studies in other tumor types are also underway.

Rubraca is an unlicensed medical product outside of the US and Europe.

Rubraca Ovarian Cancer US FDA Approved Indication

Rubraca is indicated for the maintenance treatment of adult women with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy.

https://www.rubraca.com/

Please Click here for full Prescribing Information for Rubraca.

About Clovis Oncology

Clovis Oncology, Inc. is a biopharmaceutical company focused on acquiring, developing, and commercializing innovative anti-cancer agents in the US, Europe, and additional international markets. Clovis Oncology targets development programs at specific subsets of cancer populations, and simultaneously develops, with partners, for those indications that require them, diagnostic tools intended to direct a compound in development to the population that is most likely to benefit from its use. Clovis Oncology is headquartered in Boulder, Colorado, with additional office locations in the US and Europe. Please visit www.clovisoncology.com for more information.

View source version on businesswire.com: https://www.businesswire.com/news/home/20220911005019/en/

Source: Clovis Oncology, Inc.

Clovis stock rises 15% as Rubraca shows survival benefit as maintenance therapy for ovarian cancer in trial

Sep. 12, 2022 6:48 AM ET Clovis Oncology, Inc. (CLVS)

By: Ravikash, SA News Editor

Clovis Oncology (NASDAQ:CLVS) said Rubraca as initial maintenance therapy improved progression-free survival (PFS), compared to placebo across disease risk subgroups in patients with ovarian cancer.
https://seekingalpha.com/news/3881900-clovis-stock-rises-as-rubraca-shows-survival-benefit-as-maintenance-therapy-for-ovarian-cancer-in-trial
https://seekingalpha.com/symbol/CLVS
https://clovisoncology.com/
https://www.rubraca.com/

What is Rubraca used for? Rubraca tablets are a prescription medicine used in adults for: the maintenance treatment of ovarian cancer, fallopian tube cancer, or primary peritoneal cancer whose cancer has come back and who are in response (complete or partial response) to a platinum-based chemotherapy. the treatment of castration-resistant prostate cancer (prostate cancer that no longer responds to medical or surgical treatment that lowers testosterone): that has spread to other parts of the body, and has a certain type of inherited (germline) or acquired (somatic) abnormal BRCA gene, and you have been treated with certain medicines for your cancer. Rubraca was approved based on response rate and how long patients’ responses lasted. There are ongoing studies to confirm the clinical benefit of Rubraca. Your healthcare provider will perform a test to make sure Rubraca is right for you. It is not known if Rubraca is safe and effective in children.

ENHERTU® (fam-trastuzumab deruxtecan-nxki) for injection

PADCEV® (enfortumab vedotin-ejfv) With KEYTRUDA® (pembrolizumab)

ENHERTU® (fam-trastuzumab deruxtecan-nxki) for injection

Enhertu continues to demonstrate clinically meaningful tumour response in patients with HER2-mutant metastatic non-small cell lung cancer

PUBLISHED11 September 2022

11 September 2022 09:15 BST

DESTINY-Lung02 Phase II trial shows clinically meaningful efficacy and favourable safety at 5.4mg/kg vs. 6.4mg/kg dose of AstraZeneca and Daiichi Sankyo’s Enhertu in HER2-mutant disease

Updated results from DESTINY-Lung01 Phase II trial demonstrate continued durable activity across patient subtypes

Detailed positive results from an interim analysis of the DESTINY-Lung02 Phase II trial showed Enhertu (trastuzumab deruxtecan) demonstrated clinically meaningful tumour responses in previously-treated patients with HER2-mutant (HER2m) unresectable and/or metastatic non-squamous non-small cell lung cancer (NSCLC). Results will be presented today as a late-breaking presentation at the European Society for Medical Oncology (ESMO) Congress 2022.

Enhertu is a specifically engineered HER2-directed antibody drug conjugate (ADC) being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.

At a pre-specified interim analysis of DESTINY-Lung02, patients receiving Enhertu at a dose of 5.4mg/kg or 6.4mg/kg demonstrated clinically meaningful activity. The safety profile for both doses was also consistent with the overall safety profile of Enhertu, with the 5.4mg/kg dose demonstrating a favourable safety profile in this patient population. A confirmed objective response rate (ORR) of 53.8% (95% confidence interval [CI] 39.5-67.8) and 42.9% (95% CI 24.5-62.8) was seen in the 5.4mg/kg and 6.4mg/kg arms respectively, as assessed by blinded independent central review (BICR). One complete response (CR) was observed in each arm (5.4mg/kg: 1.9%, 6.4mg/kg: 3.6%), with 27 (51.9%) partial responses (PR) observed in the 5.4mg/kg arm and 11 (39.3%) PRs observed in the 6.4mg/kg arm.

Koichi Goto, MD, Medical Oncologist and Investigator at National Cancer Center Hospital East, Kashiwa, Japan, said: “DESTINY-Lung02 reinforces HER2 as an actionable mutation in patients with metastatic non-small cell lung cancer and further demonstrates that Enhertu provides a clinically meaningful tumour response for these patients who have historically had limited treatment options. The response seen in this trial, along with the disease control observed support Enhertu as a potential treatment option in this type of non-small cell lung cancer.”

Cristian Massacesi, Chief Medical Officer & Oncology Chief Development Officer, AstraZeneca, said: “The clinically meaningful activity, together with the favourable safety profile seen in the DESTINY-Lung02 trial helps establish the optimal dose of Enhertu at 5.4 milligrams per kilogram in previously-treated HER2-mutant non-small cell lung cancer. As we continue to explore the potential of this important medicine across multiple HER2-targetable tumour types, these data reaffirm the need to undertake HER2 testing in patients diagnosed with lung cancer.”

Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo, said: “The DESTINY-Lung02 results are consistent with the data previously seen with Enhertu in non-small cell lung cancer and the efficacy demonstrated in this interim analysis, which supported the recent US FDA accelerated approval of Enhertu in patients with HER2-mutant non-small cell lung cancer, reinforces the potential to establish this medicine as a treatment option for these patients. These data will help inform future regulatory submissions worldwide with the goal of continuing to offer this innovative medicine to as many patients as possible.”

DESTINY-Lung01 updated results
Updated results from the DESTINY-Lung01 Phase II trial, which evaluated Enhertu in HER2m (cohort 2) or HER2-over-expressing (cohort 1 and cohort 1a) NSCLC, were also presented at ESMO and showed that Enhertu continues to demonstrate consistent efficacy, safety and survival with longer follow-up.

After a median follow-up of 16.7 months, results of previously treated patients with HER2m NSCLC (cohort 2) showed the median DoR for Enhertu in the overall patient population increased to 10.6 months (95% CI 5.6-18.3), with median overall survival (OS) increasing to 18.6 months (95% CI 13.8-25.8). Subgroup analyses of patients with or without a presence of baseline asymptomatic brain metastases showed that treatment with Enhertu resulted in a median PFS of 7.1 months (95% CI 5.5-9.8) and 9.7 months (95% CI 4.5-16.9) respectively, and a median OS of 14.0 months (95% CI: 9.8-19.5) and 27.0 months (95% CI: 15.3-NE), respectively. The subgroup analysis of patients who had received either two or fewer prior therapies or more than two prior therapies showed a median PFS of 8.3 months (95% CI: 5.8-15.2) and 6.8 months (95% CI: 4.4-9.8) respectively, and a median OS of 22.1 months (95% CI: 14.0-31.3) and 13.8 months (95% CI: 7.1-18.6), respectively.

Additionally, updated results from cohort 1 (Enhertu 6.4mg/kg) and cohort 1a (Enhertu 5.4mg/kg), which evaluated patients with previously-treated metastatic HER2-overexpressing NSCLC, highlight encouraging anti-tumour activity. In cohort 1, a confirmed ORR of 26.5% (95% CI 15.0-41.1) was seen in patients receiving Enhertu 6.4mg/kg, with a median progression-free survival (PFS) of 5.7 months (95% CI 2.8-7.2) and a median OS of 12.4 months (95% CI 7.8-17.2). In cohort 1a, a confirmed ORR of 34.1% (95% CI 20.1-50.6) was seen in patients receiving Enhertu 5.4mg/kg, with a median PFS of 6.7 months (95% CI 4.2-8.4), and a median OS of 11.2 months (95% CI 8.4-NE).

The overall safety profile of Enhertu in DESTINY-Lung01 was consistent with previous data, with no new safety signals identified with the longer follow-up. In the HER2m NSCLC patient cohort, there was one additional case of treatment-related ILD or pneumonitis observed, as determined by an independent adjudication committee. ILD has been observed in 27.5% of patients treated with Enhertu 6.4mg/kg in the HER2m cohort, with the majority identified as low Grade, and two Grade 5 events reported. In the HER2-overexpressing NSCLC patient cohorts, there were two additional cases of treatment-related ILD or pneumonitis observed in the 6.4mg/kg dose cohort, and two cases observed in the 5.4mg/kg dose cohort, as determined by an independent adjudication committee. ILD has been observed in 20.4% and 4.9% of patients treated with Enhertu at the 6.4mg/kg and 5.4mg/kg doses respectively in the HER2-overexpressing cohort, with the majority identified as low Grade, and four Grade 5 events (three in the 6.4mg/kg dose cohort and one in the 5.4mg/kg dose cohort) reported. Data from the DESTINY-Lung01 Phase II trial were previously published in The New England Journal of Medicine.1

DESTINY-Lung02
DESTINY-Lung02 is a global, randomised, Phase II trial evaluating the safety and efficacy of Enhertu in patients with HER2m metastatic NSCLC with disease recurrence or progression during or after at least one regimen of prior anticancer therapy that must have contained a platinum-based chemotherapy. Patients were randomised 2:1 to receive Enhertu 5.4mg/kg (n=102) or Enhertu 6.4mg/kg (n=50).The primary endpoint of the trial is confirmed ORR as assessed by BICR. Secondary endpoints include confirmed disease control rate (DCR), DoR and PFS assessed by investigator and BICR, investigator-assessed OS and safety. DESTINY-Lung02 enrolled 152 patients at multiple sites, including Asia, Europe and North America. For more information about the trial, visit ClinicalTrials.gov.

DESTINY-Lung01
DESTINY-Lung01 is a global Phase II, open-label, two-cohort trial evaluating the efficacy and safety of Enhertu (5.4mg/kg or 6.4mg/kg) in patients with HER2m (cohort 2, n=91) or HER2-overexpressing (defined as IHC 3+ or IHC 2+) [cohort 1 and 1a, n=90] unresectable or metastatic non-squamous NSCLC who had progressed after one or more systemic therapies. The primary endpoint is confirmed ORR by independent central review. Key secondary endpoints include DoR, DCR, PFS, OS and safety. DESTINY-Lung01 enrolled 181 patients at multiple sites, including Asia, Europe and North America. For more information about the trial, visit ClinicalTrials.gov.

Enhertu
Enhertu is a HER2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, Enhertu is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced programme in AstraZeneca’s ADC scientific platform. Enhertu consists of a HER2 monoclonal antibody attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a stable tetrapeptide-based cleavable linker.

Enhertu (5.4mg/kg) is approved in more than 30 countries for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received a (or one or more) prior anti-HER2-based regimen either in the metastatic setting, or in the neoadjuvant or adjuvant setting and have developed disease recurrence during or within six months of completing therapy based on the results from the DESTINY-Breast03 trial.

Enhertu (5.4mg/kg) is approved in several countries for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens based on the results from the DESTINY-Breast01 trial.

Enhertu (5.4mg/kg) is approved in the US for the treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial.

Enhertu (5.4mg/kg) is approved under accelerated approval in the US for the treatment of adult patients with unresectable or metastatic NSCLC whose tumours have activating HER2 (ERBB2) mutations, as detected by a FDA-approved test, and who have received a prior systemic therapy based on the results from the DESTINY-Lung02 trial. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Enhertu (6.4mg/kg) is approved in several countries for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 trial.

https://www.enhertu.com/

Enhertu development programme
A comprehensive development programme is underway globally, evaluating the efficacy and safety of Enhertu monotherapy across multiple HER2-targetable cancers, including breast, gastric, lung and colorectal cancers. Trials in combination with other anticancer treatments, such as immunotherapy, are also underway.

Regulatory applications for Enhertu in breast and gastric cancer are currently under review in several countries based on the DESTINY-Breast01, DESTINY-Breast03, DESTINY-Breast04, DESTINY-Gastric01 and DESTINY-Gastric02 trials, respectively.

Daiichi Sankyo collaboration
Daiichi Sankyo Company, Limited (TSE: 4568) [referred to as Daiichi Sankyo] and AstraZeneca entered into a global collaboration to jointly develop and commercialise Enhertu (a HER2-directed ADC) in March 2019 and datopotamab deruxtecan (a TROP2-directed ADC) in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights. Daiichi Sankyo is responsible for the manufacturing and supply of Enhertu and datopotamab deruxtecan.

AstraZeneca in lung cancer
AstraZeneca is working to bring patients with lung cancer closer to cure through the detection and treatment of early-stage disease, while also pushing the boundaries of science to improve outcomes in the resistant and advanced settings. By defining new therapeutic targets and investigating innovative approaches, the Company aims to match medicines to the patients who can benefit most.

The Company’s comprehensive portfolio includes leading lung cancer medicines and the next wave of innovations, including Tagrisso (osimertinib) and Iressa (gefitinib); Imfinzi (durvalumab) and tremelimumab; Enhertu (trastuzumab deruxtecan) and datopotamab deruxtecan in collaboration with Daiichi Sankyo; Orpathys (savolitinib) in collaboration with HUTCHMED; as well as a pipeline of potential new medicines and combinations across diverse mechanisms of action.

AstraZeneca is a founding member of the Lung Ambition Alliance, a global coalition working to accelerate innovation and deliver meaningful improvements for people with lung cancer, including and beyond treatment.

AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.

AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on Twitter @AstraZeneca.

AstraZeneca, Daiichi Sankyo's Enhertu shows response in lung cancer patients in trial

Sep. 12, 2022 7:49 AM ET

AstraZeneca PLC (AZN), DSKYF, DSNKY

By: Ravikash, SA News Editor

AstraZeneca (NASDAQ:AZN) and Daiichi Sankyo (OTCPK:DSKYF) (OTCPK:DSNKY) said their drug Enhertu showed clinically meaningful tumor responses in previously-treated patients with HER2-mutant (HER2m) unresectable and/or metastatic non-squamous non-small cell lung cancer (NSCLC) in a phase 2 trial.

https://seekingalpha.com/news/3881924-astrazeneca-daiichi-sankyos-enhertu-shows-response-in-lung-cancer-patients-in-trial

https://seekingalpha.com/symbol/DSKYF

https://seekingalpha.com/symbol/DSNKY

https://seekingalpha.com/symbol/AZN

https://www.enhertu.com/

What is ENHERTU? ENHERTU (en-HER-too) is a prescription medicine used to treat adults who have: Human epidermal growth factor receptor 2 (HER2)-positive breast cancer that cannot be removed by surgery or that has spread to other parts of the body (metastatic), and who have received a prior anti-HER2 breast cancer treatment: For metastatic disease, or Have breast cancer that has come back during or within 6 months of completing treatment for their early-stage breast cancer. HER2-low breast cancer that cannot be removed by surgery or that has spread to other parts of your body (metastatic), and who have received a prior chemotherapy: For metastatic disease, or Your disease has returned during or within 6 months of completing adjuvant chemotherapy (after surgery). Your healthcare provider will perform a test to make sure ENHERTU is right for you. Non-small cell lung cancer (NSCLC) that has a certain mutation in the HER2 gene and cannot be removed by surgery or has spread to other parts of your body (metastatic), and who have received a prior treatment. Your healthcare provider will perform a test to make sure ENHERTU is right for you. ENHERTU was FDA approved for this use based on a clinical study that measured how many patients responded and how long they responded. ENHERTU is still being studied to confirm these results. Stomach cancer called gastric or gastroesophageal junction (GEJ) adenocarcinoma that is HER2-positive and has spread to areas near your stomach (locally advanced) or that has spread to other parts of your body (metastatic), and who have received a prior trastuzumab-based regimen. It is not known if ENHERTU is safe and effective in children.

BIOTECNOVA™

Imfinzi (durvalumab) and tremelimumab with chemotherapy

Imfinzi and tremelimumab with chemotherapy demonstrated sustained survival benefit in metastatic non-small cell lung cancer, nearly doubling the number of patients alive after three years vs. chemotherapy

PUBLISHED11 September 2022 11 September 2022 9:20 BST

Exploratory analysis from POSEIDON Phase III trial also showed trends for overall survival benefit with a limited course of tremelimumab added to Imfinzi and chemotherapy in subgroups with high unmet need

Updated results after approximately four years of follow-up of the POSEIDON Phase III trial showed a limited course of tremelimumab when added to AstraZeneca’s Imfinzi (durvalumab) plus four cycles of chemotherapy demonstrated a sustained improvement in overall survival (OS) compared to chemotherapy alone in the 1st-line treatment of patients with Stage IV (metastatic) non-small cell lung cancer (NSCLC). Additional post-hoc, exploratory analyses continued to show a trend for OS improvement with this combination in patients with STK11, KEAP1 and KRAS-mutated NSCLC, as well as in patients whose tumours were PD-L1-negative (less than 1% tumour cell expression).

These late-breaking results were presented today at the European Society of Medical Oncology (ESMO) Congress 2022 (Abstract #LBA59).

KRAS mutations are the most common tumour growth driver in NSCLC, occurring in approximately 25% of patients. NSCLC tumours with STK11 and KEAP1 mutations are often associated with poor outcomes and classified as immunologically “cold.” KRAS-mutated NSCLC can be responsive to immunotherapy but also can have poor outcomes, particularly when associated with STK11 or KEAP1 co-mutations.1-6

Melissa Johnson, MD, Director of Lung Cancer Research, Sarah Cannon Research Institute at Tennessee Oncology in Nashville, Tennessee, and a lead investigator in the POSEIDON Phase III trial, said: "Metastatic non-small cell lung cancer is a devastating diagnosis, particularly for patients whose cancers are less responsive to standard treatments such as chemotherapy and immune therapy. These results support the addition of a limited course of tremelimumab to durvalumab plus chemotherapy as a potential new treatment option for patients with these harder-to-treat forms of lung cancer.”

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: "These updated POSEIDON results at nearly four years of follow-up show further evidence that the addition of a limited course of tremelimumab to Imfinzi plus chemotherapy improves outcomes for metastatic non-small cell lung cancer patients, including those with specific tumour mutations where a high unmet need for effective, well tolerated treatments remains. We look forward to bringing this potential new treatment option to patients as quickly as possible."

These latest data show that a limited course of five cycles of tremelimumab added to Imfinzi plus platinum-based chemotherapy improved overall survival by 25% compared to chemotherapy alone (hazard ratio [HR] 0.75; 95% CI 0.63-0.88). Updated median OS was 14 months for the combination versus 11.7 for chemotherapy alone. An estimated 25% of patients treated with the combination were alive at three years versus 13.6% for those treated with chemotherapy alone.

A trend for OS improvement continued to be observed in patients with STK11, KEAP1, and KRAS-mutated mNSCLC when treated with the combination, which reduced the risk of death by 38% (based on a HR of 0.62; 95% CI 0.34-1.12), 57% (based on a HR of 0.43; 95% CI 0.16-1.25), and 45% (based on a HR of 0.55; 95% CI 0.36-0.85), respectively. The combination also extended sustained OS benefit to patients with less than 1% PD-L1 tumour cell expression. These post hoc, exploratory subgroup analyses should be interpreted with caution due to the small sample sizes.

Consistent with previous POSEIDON Phase III trial readouts, OS benefit in these updated results appeared more pronounced with tremelimumab plus Imfinzi and chemotherapy in patients with non-squamous NSCLC histology. A 32% improvement in OS compared to chemotherapy alone (HR 0.68; 95% CI 0.55–0.85) was reported for patients with non-squamous histology, with an updated median OS of 17.2 months for the combination versus 13.1 months for chemotherapy. An estimated 31.4% of patients with non-squamous NSCLC treated with the combination were alive at three years versus 17.3% for those receiving chemotherapy alone.

Tremelimumab plus Imfinzi and chemotherapy continued to be well-tolerated, with no new safety signals identified based on the collection of serious adverse events (AEs) during the approximately four years of follow-up. Serious treatment-related AEs of any grade occurred in 27.6% of patients in the Imfinzi, tremelimumab and chemotherapy arm versus 17.7% in the chemotherapy alone arm as assessed by investigators. Treatment-related AEs leading to death occurred in 3.3% of patients in the combination arm versus 2.4% in the chemotherapy arm.

These updated results build on the primary progression-free survival (PFS) and OS results presented at the 2021 World Conference on Lung Cancer (WCLC) in September 2021 as well as post-hoc exploratory results in patients with STK11, KEAP1 or KRAS-mutated metastatic NSCLC recently presented at WCLC 2022 in August.

Tremelimumab is under review by global regulatory authorities in combination with Imfinzi and chemotherapy in 1st-line metastatic NSCLC based on the results of the POSEIDON trial.

POSEIDON
The POSEIDON trial was a randomised, open-label, multi-centre, global, Phase III trial of Imfinzi plus platinum-based chemotherapy or Imfinzi, tremelimumab and chemotherapy versus chemotherapy alone in the 1st-line treatment of 1,013 patients with metastatic NSCLC. The trial population included patients with either non-squamous or squamous disease and the full range of PD-L1 expression levels. POSEIDON excluded patients with certain epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) fusions.

In the experimental arms, patients were treated with a flat dose of 1,500mg of Imfinzi, or Imfinzi and 75mg of tremelimumab with up to four cycles of chemotherapy every three weeks, followed by maintenance treatment with Imfinzi once every four weeks, or Imfinzi and a fifth dose of 75mg of tremelimumab given at week 16. In comparison, the control arm allowed up to six cycles of chemotherapy. Pemetrexed maintenance treatment was allowed in all arms in patients with non-squamous disease if given during the induction phase. Nearly all patients with non-squamous disease (95.5%) had pemetrexed and platinum, while the majority of patients with squamous disease receiving chemotherapy (88.3%) received gemcitabine and platinum.

Primary endpoints included PFS and OS for the Imfinzi plus chemotherapy arm. Key secondary endpoints included PFS and OS in the Imfinzi plus tremelimumab and chemotherapy arm. As both PFS endpoints were met for Imfinzi plus chemotherapy and Imfinzi, tremelimumab and chemotherapy, the prespecified statistical analysis plan allowed for testing OS in the Imfinzi plus tremelimumab and chemotherapy arm. The trial was conducted in more than 150 centres across 18 countries, including the US, Europe, South America, Asia and South Africa.

Imfinzi
Imfinzi (durvalumab) is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, countering the tumour's immune-evading tactics and releasing the inhibition of immune responses.

Imfinzi is the only approved immunotherapy in the curative-intent setting of unresectable, Stage III non-small cell lung cancer (NSCLC) in patients whose disease has not progressed after chemoradiotherapy, and is the global standard of care in this setting based on the PACIFIC Phase III trial.

Imfinzi is currently approved in a number of countries in multiple tumour types including for the treatment of extensive-stage small cell lung cancer (ES-SCLC); for previously treated patients with advanced bladder cancer and for locally advanced or metastatic BTC in combination with chemotherapy (gemcitabine plus cisplatin).

Since the first approval in May 2017, more than 100,000 patients have been treated with Imfinzi.

Imfinzi combinations have demonstrated clinical benefit in multiple additional cancer settings with positive Phase III trials in unresectable advanced liver cancer (HIMALAYA), metastatic NSCLC (POSEIDON) and resectable NSCLC (AEGEAN). The data from HIMALAYA and POSEIDON are under review with global health authorities.

As part of a broad development programme, Imfinzi is being tested as a single treatment and in combinations with other anti-cancer treatments for patients with SCLC, NSCLC, bladder cancer, several GI cancers, ovarian cancer, endometrial cancer and other solid tumours. 

https://www.imfinzi.com/

Tremelimumab
Tremelimumab is a human monoclonal antibody and potential new medicine that targets the activity of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). Tremelimumab blocks the activity of CTLA-4, contributing to T-cell activation, priming the immune response to cancer and fostering cancer cell death.

Beyond POSEIDON, tremelimumab is being tested in combination with Imfinzi across multiple tumour types including in bladder cancer (VOLGA and NILE), locoregional HCC (EMERALD-3) and SCLC (ADRIATIC).

Tremelimumab is also under review by global regulatory authorities in combination with Imfinzi in unresectable advanced liver cancer based on the results of the HIMALAYA Phase III trial.

The Company's comprehensive portfolio includes leading lung cancer medicines and the next wave of innovations, including Tagrisso (osimertinib) and Iressa (gefitinib); Imfinzi (durvalumab) and tremelimumab; Enhertu (trastuzumab deruxtecan) and datopotamab deruxtecan in collaboration with Daiichi Sankyo; Orpathys (savolitinib) in collaboration with HUTCHMED; as well as a pipeline of potential new medicines and combinations across diverse mechanisms of action.

AstraZeneca in immuno-oncology (IO)
Immunotherapy is a therapeutic approach designed to stimulate the body’s immune system to attack tumours. The Company’s Immuno-Oncology (IO) portfolio is anchored in immunotherapies that have been designed to overcome evasion of the anti-tumour immune response. AstraZeneca is invested in using IO approaches that deliver long-term survival for new groups of patients across tumour types.

The Company is pursuing a comprehensive clinical-trial programme that includes Imfinzi as a single treatment and in combination with tremelimumab and other novel antibodies in multiple tumour types, stages of disease, and lines of treatment, and where relevant using the PD-L1 biomarker as a decision-making tool to define the best potential treatment path for a patient.

In addition, the ability to combine the IO portfolio with radiation, chemotherapy, and targeted small molecules from across AstraZeneca’s oncology pipeline, and from research partners, may provide new treatment options across a broad range of tumours.

AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.

AstraZeneca Imfinzi/tremelimumab combo shows survival benefit in lung cancer in 4-year data

Sep. 12, 2022 7:17 AM ET

AstraZeneca PLC (AZN)

By: Ravikash, SA News Editor

AstraZeneca (NASDAQ:AZN) said ~4 years of follow-up data from a phase 3 trial suggested that a limited five cycles of tremelimumab added to Imfinzi (durvalumab) plus four cycles of chemotherapy improved overall survival (OS) by 25% compared to chemotherapy alone as initial treatment of patients with stage IV (metastatic) non-small cell lung cancer (NSCLC).

https://seekingalpha.com/news/3881911-astrazeneca-imfinzitremelimumab-combo-shows-survival-benefit-in-lung-cancer-in-4-year-data

https://seekingalpha.com/symbol/AZN

https://www.imfinzi.com/

https://www.astrazeneca.com/

Imfinzi plus chemotherapy further improved overall survival benefit in advanced biliary tract cancer in the TOPAZ-1 Phase III trial, reducing the risk of death by 24% in additional follow-up

PUBLISHED12 September 2022 12 September 2022 07:00 BST

HIMALAYA Phase III trial exploratory results support the benefit of tremelimumab
added to Imfinzi in unresectable liver cancer regardless of aetiology

Updated results from the TOPAZ-1 Phase III trial showed AstraZeneca’s Imfinzi (durvalumab), in combination with standard-of-care chemotherapy demonstrated a clinically meaningful and durable overall survival (OS) benefit as a treatment for patients with advanced biliary tract cancer (BTC).

These results from TOPAZ-1, the first Phase III trial to show improved OS with an immunotherapy combination in this setting, will be presented today at the European Society for Medical Oncology (ESMO) Congress 2022 in Paris (abstract #56P).

https://www.astrazeneca.com/media-centre/press-releases/2022/imfinzi-plus-chemotherapy-further-improved-overall-survival-benefit-in-advanced-biliary-tract-cancer-in-the-topaz-1-phase-iii-trial.html

AstraZeneca Imfinzi combo cuts risk of death by 24% in biliary tract cancer patients in trial

Sep. 12, 2022 5:30 AM ET

AstraZeneca PLC (AZN)

By: Ravikash, SA News Editor

AstraZeneca (NASDAQ:AZN) said Imfinzi, in combination with standard-of-care chemotherapy, showed a clinically meaningful and durable overall survival (OS) benefit for patients with advanced biliary tract cancer (BTC) in a phase 3 trial called TOPAZ-1.

https://seekingalpha.com/news/3881886-astrazeneca-imfinzi-combo-cuts-risk-of-death-by-24-in-biliary-tract-cancer-patients-in-trial

https://seekingalpha.com/symbol/AZN

https://www.imfinzi.com/

What is IMFINZI? IMFINZI is a prescription medicine used to treat adults with a type of lung cancer called non-small cell lung cancer (NSCLC). IMFINZI may be used when your NSCLC has not spread outside your chest, cannot be removed by surgery, and has responded or stabilized with initial treatment with chemotherapy that contains platinum, given at the same time as radiation therapy. IMFINZI is a prescription medicine used to treat adults with a type of lung cancer called small cell lung cancer (SCLC). IMFINZI may be used with the chemotherapy medicines etoposide and carboplatin or cisplatin as your first treatment when your SCLC has spread within your lungs or to other parts of the body (extensive-stage small cell lung cancer, or ES-SCLC). IMFINZI is a prescription medicine used to treat adults with a type of cancer called biliary tract cancer (BTC), including cancer of the bile ducts (cholangiocarcinoma) and gallbladder cancer. IMFINZI may be used in combination with chemotherapy medicines gemcitabine and cisplatin when your BTC has spread to nearby tissues (locally advanced), or has spread to other parts of the body (metastatic). It is not known if IMFINZI is safe and effective in children.

Lynparza (olaparib) in combination with bevacizumab

Imfinzi (durvalumab) and tremelimumab with chemotherapy

Lynparza in combination with bevacizumab, and as a monotherapy, demonstrates clinically meaningful survival benefit in 1st-line advanced ovarian cancer across two Phase III trials

PUBLISHED9 September 2022 09 September 2022 13:10 BST

Landmark 5-year follow-up of PAOLA-1 Phase III trial demonstrated Lynparza plus bevacizumab meaningfully extended survival with 65.5% of HRD-positive patients surviving 5 years vs. 48.4% treated with bevacizumab and placebo

SOLO-1 Phase III trial demonstrated 67% of advanced ovarian cancer patients with BRCA mutations treated with Lynparza were alive at 7 years vs. 47% on placebo

Positive long-term follow-up results from the PAOLA-1 and SOLO-1 Phase III trials of AstraZeneca and MSD’s Lynparza (olaparib) with or without bevacizumab demonstrated clinically meaningful improvements in overall survival (OS). Further results showed class-leading progression-free survival (PFS) in combination with bevacizumab for homologous recombination deficiency (HRD)-positive patients, versus active comparator, bevacizumab, and as monotherapy for patients with BRCA mutations, versus placebo, respectively.

Both trials which were conducted in biomarker-selected, newly diagnosed patients with advanced ovarian cancer in the 1st-line maintenance setting also demonstrated a consistent safety profile.1,2

The results for PAOLA-1 (Abstract #LBA29) and SOLO-1 (Abstract #517O) were presented on 9 September at the 2022 European Society of Medical Oncology (ESMO) and SOLO-1 results were published in Journal of Clinical Oncology.

Ovarian cancer is one of the most common gynaecologic cancers, with a poor prognosis and a high mortality rate.3 Over two thirds of patients are diagnosed with advanced disease, and approximately 50-70% of these patients die within five years.4,5 Up to one in five women with advanced ovarian cancer have a BRCA mutation, and roughly half of women have HRD-positive tumours (which includes those with a BRCA mutation).6-8

Professor Isabelle Ray-Coquard, principal investigator from the PAOLA-1 trial and President of the Gineco group, said: “For women facing an advanced ovarian cancer diagnosis who are HRD-positive, a targeted treatment in the 1st-line maintenance setting is critical to helping them live longer. These latest results at the five-year landmark demonstrate that olaparib with bevacizumab reduces the risk of death by 38% in HRD-positive patients compared to bevacizumab alone, further reinforcing the clinically meaningful long-term survival benefit of this combination. This should be promising news for both clinicians and patients, as we see these additional data show that this combination may allow patients more time with family and loved ones. These results also highlight the importance of biomarker testing as part of a precision medicine approach to guide treatment decisions in ovarian cancer patients.”

Professor Paul DiSilvestro, investigator from the SOLO-1 trial and Director of the Program in Women’s Oncology at Women and Infants Hospital in Providence, Rhode Island, said: “The long-term results from SOLO-1 confirm that olaparib continues to elicit a clinically meaningful improvement in overall survival in the 1st-line maintenance setting for more than seven years. Achieving long-term survival for patients with newly diagnosed advanced ovarian cancer is critical because the 1st-line setting offers the greatest potential to impact patient survival.”

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “Historically the five year survival rate of newly diagnosed patients with advanced ovarian cancer is 30-50%. In that context, it is phenomenal to share the long term overall survival data from both PAOLA-1 and SOLO-1, with two out of three patients still alive in these trials. We continue to believe in Lynparza’s ability to help biomarker-selected patients with advanced ovarian cancer to achieve better outcomes.”

Dr Eliav Barr, Senior Vice President, Head of Global Clinical Development and Chief Medical Officer, MSD Research Laboratories, said: “These latest data from the PAOLA-1 and SOLO-1 trials further highlight the importance of HRD testing, including for BRCA1/2 mutations, for all newly diagnosed advanced ovarian cancer patients at the point of diagnosis. Maintenance therapy with Lynparza may provide certain patients with HRD-positive and/or BRCA-mutated advanced ovarian cancer the opportunity to live longer.”

Updated results from the PAOLA-1 Phase III trial
Updated results from the PAOLA-1 Phase III trial demonstrate that Lynparza plus bevacizumab increased median overall survival to 56.5 months versus 51.6 months with bevacizumab alone, in patients with newly diagnosed advanced ovarian cancer irrespective of HRD status. This increase was not statistically significant.

In HRD-positive patients, Lynparza plus bevacizumab provided a clinically meaningful improvement in overall survival, reducing the risk of death by 38% versus bevacizumab (based on a HR of 0.62; 95% CI 0.45-0.85) despite PAOLA-1 having 30% Stage IV patients. 65.5% of patients treated with Lynparza plus bevacizumab were still alive at five years versus 48.4% of those treated with bevacizumab alone. Lynparza plus bevacizumab also improved median PFS to almost four years (46.8 months) versus 17.6 months with bevacizumab plus placebo and 46.1% of patients treated with Lynparza plus bevacizumab remain progression free at five years versus 19.2% of patients treated with bevacizumab alone. The safety and tolerability profile of Lynparza in this trial was in line with that observed in prior clinical trials, with no new safety signals.

Updated results from the SOLO-1 Phase III trial
Updated results from the SOLO-1 Phase III trial demonstrate that Lynparza provided a clinically meaningful improvement in overall survival (OS) versus placebo in patients with BRCA-mutated (BRCAm) newly diagnosed advanced ovarian cancer, reducing the risk of death by 45% (based on an HR of 0.55; 95% CI 0.40-0.76; nominal p=0.0004 [not statistically significant]). Median OS was still not reached with Lynparza versus 75.2 months with placebo. At the seven-year descriptive OS analysis, 67% of Lynparza patients were alive versus 47% of placebo patients (44% of whom had a subsequent PARP inhibitor) and 45% of Lynparza patients versus 21% of placebo patients were alive and had not received a first subsequent treatment.

Additional data showed median time to first subsequent therapy was 64 months with Lynparza versus 15.1 months with placebo. The safety and tolerability profile of Lynparza in this trial was in line with that observed in prior clinical trials, with no new safety signals.

PAOLA-1
PAOLA-1 is a double-blinded Phase III trial testing the efficacy and safety of Lynparza added to standard-of-care bevacizumab versus bevacizumab alone, as a 1st-line maintenance treatment for newly diagnosed advanced FIGO Stage III-IV high-grade serous or endometroid ovarian, fallopian tube, or peritoneal cancer patients who had a complete or partial response to 1st-line treatment with platinum-based chemotherapy and bevacizumab. AstraZeneca and MSD announced in August 2019 that the trial met its primary endpoint of PFS in the overall trial population.

PAOLA-1 is an ENGOT (European Network of Gynaecological Oncological Trial groups) trial, sponsored by ARCAGY Research (Association de Recherche sur les CAncers dont GYnécologiques) on behalf of GINECO (Groupe d’Investigateurs National des Etudes des Cancers Ovariens et du sein). ARCAGY-GINECO is an academic group specialising in clinical and translational research in patients’ cancers and a member of the GCIG (Gynecologic Cancer InterGroup).

SOLO-1
SOLO-1 is a Phase III randomised, double-blinded, placebo-controlled, multicentre trial to evaluate the efficacy and safety of Lynparza tablets (300 mg twice daily) as maintenance monotherapy compared with placebo, in newly-diagnosed patients with advanced BRCAm ovarian cancer following platinum-based chemotherapy. The trial randomised 391 patients with a deleterious or suspected deleterious BRCA1 or BRCA2 mutation who were in clinical complete or partial response following platinum-based chemotherapy. Patients were randomised (2:1) to receive Lynparza or placebo for up to two years or until disease progression (at the investigator’s discretion). The primary endpoint was PFS and key secondary endpoints included time to second disease progression or death, time to first subsequent treatment and overall survival. AstraZeneca and MSD announced in June 2018 that the trial met its primary endpoint of PFS in the overall trial population.

BRCA
BRCA1 and BRCA2 are human genes that produce proteins responsible for repairing damaged DNA and play an important role maintaining the genetic stability of cells.13 When either of these genes is mutated or altered such that its protein product either is not made or does not function correctly, DNA damage may not be repaired properly, and cells become unstable. As a result, cells are more likely to develop additional alterations that can lead to cancer. Cancers with BRCA mutations are more likely to be sensitive to PARP inhibitors including Lynparza.13-16

Lynparza
Lynparza (olaparib) is a first-in-class PARP inhibitor and the first targeted treatment to block DNA damage response (DDR) in cells/tumours harbouring a deficiency in homologous recombination repair (HRR), such as those with mutations in BRCA1 and/or BRCA2, or those where deficiency is induced by other agents (such as new hormonal agents – NHAs).

Inhibition of PARP proteins with Lynparza leads to the trapping of PARP bound to DNA single-strand breaks, stalling of replication forks, their collapse and the generation of DNA double-strand breaks and cancer cell death.

Lynparza is currently approved in a number of countries across multiple tumour types including maintenance treatment of platinum-sensitive relapsed ovarian cancer and as both monotherapy and in combination with bevacizumab for the 1st-line maintenance treatment of BRCA-mutated (BRCAm) and homologous recombination repair deficient (HRD)-positive advanced ovarian cancer, respectively; for gBRCAm, HER2-negative metastatic breast cancer (in the EU and Japan this includes locally advanced breast cancer); for gBRCAm, HER2-negative high-risk early breast cancer (in Japan this includes all BRCAm HER2-negative high-risk early breast cancer); for gBRCAm metastatic pancreatic cancer; and HRR gene-mutated metastatic castration-resistant prostate cancer (BRCAm only in the EU and Japan).

Lynparza, which is being jointly developed and commercialised by AstraZeneca and MSD, is the foundation of AstraZeneca's industry-leading portfolio of potential new medicines targeting DDR mechanisms in cancer cells.

https://www.lynparza.com/

Working together, the companies will develop Lynparza and Koselugo in combination with other potential new medicines and as monotherapies. The companies will develop Lynparza and Koselugo in combination with their respective PD-L1 and PD-1 medicines independently.

AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.

AstraZeneca/Merck's Lynparza shows survival benefit in ovarian cancer patients in long-term data

Sep. 09, 2022 9:25 AM ET

AstraZeneca PLC (AZN), MRKRHHBY, RHHBF

By: Ravikash, SA News Editor

AstraZeneca (NASDAQ:AZN) and Merck's (NYSE:MRK) Lynparza showed clinically meaningful survival benefit as first line therapy in certain patients with ovarian cancer as per long-term data from two phase 3 trials.

https://seekingalpha.com/news/3881639-astrazenecamercks-lynparza-shows-survival-benefit-in-ovarian-cancer-patients-in-long-term-data

https://seekingalpha.com/symbol/AZN

https://seekingalpha.com/symbol/MRK

https://www.lynparza.com/

Trodelvy® (sacituzumab govitecan-hziy)

Imfinzi (durvalumab) and tremelimumab with chemotherapy

Trodelvy® (sacituzumab govitecan-hziy)

September 07, 2022

Trodelvy® Significantly Improved Overall Survival in Pre-Treated HR+/HER2- Metastatic Breast Cancer Patients in TROPiCS-02 Study

-- 3.2 Month Survival Benefit Demonstrated in Patients who had Already Received Prior Endocrine-based Therapy and at Least Two Prior Chemotherapies --

-- Trodelvy Now Shows a Survival Benefit in both Pre-treated HR+/HER2- Metastatic Breast Cancer and Second-Line Metastatic Triple-Negative Breast Cancer --

FOSTER CITY, Calif.--(BUSINESS WIRE)-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced the positive overall survival (OS) results from the Phase 3 TROPiCS-02 study evaluating Trodelvy® (sacituzumab govitecan-hziy) versus comparator chemotherapy (physicians’ choice of chemotherapy, TPC) in patients with HR+/HER2- metastatic breast cancer who received endocrine-based therapies and at least two chemotherapies. In the study, Trodelvy demonstrated a statistically significant and clinically meaningful improvement of 3.2 months in OS compared to TPC (median OS: 14.4 months vs. 11.2 months; hazard ratio [HR]=0.79; [95% confidence interval [CI]: 0.65-0.96]; p=0.02). OS was a key secondary endpoint of the trial.

These findings will be presented on Friday, September 9 at 4:20pm CEST during the European Society for Medical Oncology (ESMO) Congress 2022 as a late-breaking oral presentation (#LBA76) in the Brest Auditorium, Paris Expo Porte de Versailles.

Other key secondary endpoints including objective response rate (ORR) demonstrated statistically significant improvement in favoring Trodelvy versus TPC. Time to deterioration (TTD) of Global Health Status/Quality of Life (QoL) and Fatigue scale per EORTC-QLQ-C30 also favored Trodelvy versus TPC (QoL: 4.3 months vs. 3.0 months, p=0.006; Fatigue: 2.2 months vs. 1.4 months, p=0.002). No statistically significant difference in TTD on the Pain Scale was observed.

“It is outstanding to see a clinically meaningful survival benefit of over three months for patients with pre-treated HR+/HER2- metastatic breast cancer,” said Hope S. Rugo, MD, Professor of Medicine and Director, Breast Oncology and Clinical Trials Education at the University of California San Francisco Comprehensive Cancer Center, U.S. “Nearly all patients with HR+/HER2- metastatic breast cancer will develop resistance to endocrine-based therapies even in combination with targeted agents, so these data are welcome news for the breast cancer community. The results of TROPiCS-02 highlight the potential for sacituzumab govitecan in patients with pre-treated HR+/HER2- metastatic breast cancer.”

The safety profile for Trodelvy was consistent with prior studies, with no new safety signals identified in this patient population.

“With these data from TROPiCS-02, Trodelvy has now demonstrated a survival benefit in both pre-treated HR+/HER2- metastatic breast cancer and second-line metastatic TNBC – two difficult-to-treat forms of breast cancer,” said Bill Grossman, MD, PhD, Senior Vice President, Therapeutic Area Head, Gilead Oncology. “Our Gilead Oncology ambition is to transform care for people with cancer, and the meaningful improvement in survival benefit seen in the TROPiCS-02 study with Trodelvy is another step forward in pursuing this ambition for patients.”

The TROPiCS-02 study met its primary endpoint of progression-free survival earlier this year; detailed results were presented during the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting.

Trodelvy has not been approved by any regulatory agency for the treatment of HR+/HER2- metastatic breast cancer. Its safety and efficacy have not been established for this indication. Gilead has submitted a supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (FDA) based on data from TROPiCS-02; these data will also be shared with health authorities outside the U.S.

Sacituzumab govitecan-hziy is currently included in the National Comprehensive Cancer Network® (NCCN®) Clinical Practice Guidelines in Oncology (NCCN Guidelines®)i. This includes a Category 1 recommendation for use in adult patients with second-line metastatic triple-negative breast cancer (defined as those who received at least two prior therapies, with at least one line for metastatic disease). It also has a Category 2A preferred recommendation for investigational use in HR+/HER2- advanced breast cancer after prior treatment including endocrine therapy, a CDK4/6 inhibitor and at least two lines of chemotherapy.

Trodelvy has a Boxed Warning for severe or life-threatening neutropenia and severe diarrhea; please see below for additional Important Safety Information.

About the TROPiCS-02 Study

The TROPiCS-02 study is a global, multicenter, open-label, Phase 3 study, randomized 1:1 to evaluate Trodelvy versus physicians’ choice of chemotherapy (eribulin, capecitabine, gemcitabine, or vinorelbine) in 543 patients with HR+/HER2- metastatic breast cancer who were previously treated with endocrine therapy, CDK4/6 inhibitors and two to four lines of chemotherapy for metastatic disease. The primary endpoint is progression-free survival per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) as assessed by blinded independent central review (BICR) for participants treated with Trodelvy compared to those treated with chemotherapy. Secondary endpoints include overall survival, overall response rate, clinical benefit rate and duration of response, as well as assessment of safety and tolerability and quality of life measures. In the study, HER2 negativity was defined per American Society of Clinical Oncology (ASCO) and the College of American Pathologists (CAP) criteria as immunohistochemistry (IHC) score of 0, IHC 1+ or IHC 2+ with a negative in-situ hybridization (ISH) test. More information about TROPiCS-02 is available at https://clinicaltrials.gov/ct2/show/NCT03901339.

About Trodelvy

Trodelvy® (sacituzumab govitecan-hziy) is a first-in-class Trop-2 directed antibody-drug conjugate. Trop-2 is a cell surface antigen highly expressed in multiple tumor types, including in more than 90% of breast and bladder cancers. Trodelvy is intentionally designed with a proprietary hydrolyzable linker attached to SN-38, a topoisomerase I inhibitor payload. This unique combination delivers potent activity to both Trop-2 expressing cells and the microenvironment.

Trodelvy is approved in more than 35 countries, with multiple additional regulatory reviews underway worldwide, for the treatment of adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease. Trodelvy is also approved in the U.S. under the accelerated approval pathway for the treatment of adult patients with locally advanced or metastatic urothelial cancer (UC) who have previously received a platinum-containing chemotherapy and either programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor.

Trodelvy is also being developed for potential investigational use in other TNBC and metastatic UC populations, as well as a range of tumor types where Trop-2 is highly expressed, including hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer, metastatic non-small cell lung cancer (NSCLC), metastatic small cell lung cancer (SCLC), head and neck cancer, and endometrial cancer.

U.S. Indications for Trodelvy

In the United States, Trodelvy is indicated for the treatment of:

Adult patients with unresectable locally advanced or metastatic TNBC who have received two or more prior systemic therapies, at least one of them for metastatic disease.
Adult patients with locally advanced or metastatic UC who have previously received a platinum-containing chemotherapy and either programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
https://www.trodelvy.com/
Please see full Prescribing Information , including BOXED WARNING.

About Gilead Sciences

View source version on businesswire.com: https://www.businesswire.com/news/home/20220906006036/en/

Source: Gilead Sciences, Inc.

Gilead Trodelvy shows 3.2-month benefit for new breast cancer indication

Sep. 08, 2022 6:53 AM ET

Gilead Sciences, Inc. (GILD)

By: Dulan Lokuwithana, SA News Editor1 Comment

Gilead Sciences (NASDAQ:GILD) announced that its antibody-drug conjugate Trodelvy indicated a statistically significant and clinically meaningful improvement of 3.2 months in overall survival (OS) versus chemotherapy in certain patients with HR+/HER2- metastatic breast cancer.

https://seekingalpha.com/news/3881135-gild-stock-on-watch-after-new-breast-cancer-data-for-trodelvy

https://seekingalpha.com/symbol/GILD

https://www.trodelvy.com/

https://www.gilead.com/

WHAT IS TRODELVY? TRODELVY® (sacituzumab govitecan-hziy) is a prescription medicine used to treat adults with: triple-negative breast cancer (negative for estrogen and progesterone hormone receptors and HER2) that has spread to other parts of the body (metastatic) or cannot be removed by surgery, and who have received two or more prior treatments, including at least one treatment for metastatic disease. bladder cancer and cancers of the urinary tract that have spread or cannot be removed by surgery, and who have received a platinum-containing chemotherapy medicine and also received an immunotherapy medicine. It is not known if TRODELVY is safe and effective in people with moderate or severe liver problems or in children.

DUPIXENT® (DUPILUMAB)

Forxiga (dapagliflozin) (known as Farxiga in the US)

Trodelvy® (sacituzumab govitecan-hziy)

September 5, 2022 at 7:29 AM EDT

LATE-BREAKING DUPIXENT® (DUPILUMAB) DATA AT ERS 2022 SHOW CONSISTENT EFFICACY AND SAFETY PROFILE FOR UP TO TWO YEARS IN CHILDREN AGED 6 TO 11 YEARS WITH MODERATE-TO-SEVERE ASTHMA

Results from the longest global Phase 3 open-label extension trial in this age group in asthma show sustained improvement in lung function, low rate of asthma attacks and a consistent safety profile for up to two years

TARRYTOWN, N.Y. and PARIS, Sept. 5, 2022 /PRNewswire/ -- Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) and Sanofi today announced results from a Phase 3 open-label extension trial demonstrating the efficacy and safety profile of Dupixent® (dupilumab) as a maintenance therapy when added to other asthma medications was consistent for up to two years in children aged 6 to 11 years with uncontrolled moderate-to-severe asthma with evidence of type 2 inflammation. These results were presented today in a late-breaking session at the 2022 European Respiratory Society (ERS) International Congress, which coincides with the milestone that more than 500,000 people around the world have been treated with Dupixent across all of its approved indications.

"Children with uncontrolled moderate-to-severe asthma may experience long-term persistent coughing, difficulty breathing, unpredictable asthma attacks and impaired lung function, which can lead to complications later in life as they grow and develop," said Leonard B. Bacharier, M.D., Professor of Pediatrics and Director of the Center for Pediatric Asthma Research, Monroe Carell Jr. Children's Hospital at Vanderbilt University Medical Center in Nashville, Tennessee, and principal investigator of the trial. "An established safety profile balanced with efficacy is always a priority when treating children with a chronic disease, such as those with uncontrolled moderate-to-severe asthma with an eosinophilic phenotype or oral corticosteroid dependent asthma. These new data further support the consistent safety profile of long-term Dupixent - which is indicated for the treatment of uncontrolled moderate-to-severe asthma with an eosinophilic phenotype or oral corticosteroid dependent asthma - and its ability to provide sustained improvements in lung function and reductions in asthma exacerbations in children as young as 6 years old."

The results are from data in children who entered the extension trial after finishing active treatment or placebo in the Phase 3 trial (pivotal trial). Children in the extension trial were treated for up to an additional year with Dupixent, providing up to two years of data in total. Children treated with Dupixent in the extension trial experienced a:

Low rate of severe asthma attacks with an average of 0.118-0.124 events per year, compared to 2.16-2.56 events per year at baseline in the pivotal trial.
Sustained improvement in lung function at 52 weeks of 9.43-12.6 percentage points from baseline in the pivotal trial, measured by percent predicted FEV1 (FEV1pp). FEV1pp seeks to evaluate a patient's change in lung function compared to their predicted lung function based on age, height, sex and ethnicity to account for children's growing lung capacity at different stages of development.
- Children who switched from placebo in the pivotal trial to Dupixent in the extension trial demonstrated improvement of 8.71 percentage points in lung function at two weeks.

The safety results of the trial were generally consistent with the known safety profile of Dupixent in its approved respiratory indications. Over the 52-week treatment period, the overall rates of adverse events (AEs) were 61-68%. The most common AEs (≥5%) were nasopharyngitis (9-10%), pharyngitis (6-10%), upper respiratory tract infection (4-8%), influenza (5-6%), eosinophilia (3-6%), allergic rhinitis (3-7%), diarrhea (4-6%) and injection site reactions (3-7%).

About the LIBERTY ASTHMA EXCURSION Trial
The Phase 3, multicenter, open-label extension trial evaluated the long-term safety and efficacy of Dupixent in 365 children with uncontrolled moderate-to-severe asthma who had previously participated in the placebo-controlled VOYAGE trial (the pivotal trial) when they were 6 to 11 years of age. Based on body weight, patients in the open-label extension trial received Dupixent 100 mg or 200 mg every two weeks or Dupixent 300 mg every four weeks, for 52 weeks.

The primary endpoint assessed the number of patients experiencing any treatment emergent adverse event. Secondary endpoints included the annualized rate of severe asthma exacerbations over one year and change from pivotal trial baseline in FEV1pp.

About Dupixent
Dupixent, which was invented using Regeneron's proprietary VelocImmune® technology, is a fully human monoclonal antibody that inhibits the signaling of the interleukin-4 (IL-4) and interleukin-13 (IL-13) pathways and is not an immunosuppressant. The Dupixent development program has shown significant clinical benefit and a decrease in type 2 inflammation in Phase 3 trials, establishing that IL-4 and IL-13 are key and central drivers of the type 2 inflammation that plays a major role in multiple related and often co-morbid diseases. These diseases include approved indications for Dupixent such as asthma, atopic dermatitis, chronic rhinosinusitis with nasal polyposis (CRSwNP) and eosinophilic esophagitis (EoE), as well as investigational diseases such as prurigo nodularis.

In the EU, Dupixent is approved in children aged 6 to 11 years as an add-on maintenance treatment for severe asthma with type 2 inflammation characterized by raised blood eosinophils and/or raised FeNO, who are inadequately controlled with medium to high dose inhaled corticosteroids (ICS) plus another medicinal product for maintenance treatment. For adolescents and adults 12 years and older with severe asthma with type 2 inflammation, patients must be inadequately controlled with high dose ICS plus another medicinal product for maintenance treatment.

Dupixent has received regulatory approvals around the world for use in in certain patients with atopic dermatitis, asthma, CRSwNP or EoE in different age populations. Dupixent is currently approved across these indications in the U.S. and for one or more of these indications in more than 60 countries, including in the European Union and Japan.

https://www.dupixent.com/

Please see accompanying full

Prescribing Information including Patient Information.

About Regeneron
Regeneron is a leading biotechnology company that invents, develops and commercializes life-transforming medicines for people with serious diseases. Founded and led for nearly 35 years by physician-scientists, our unique ability to repeatedly and consistently translate science into medicine has led to numerous FDA-approved treatments and product candidates in development, almost all of which were homegrown in our laboratories. Our medicines and pipeline are designed to help patients with eye diseases, allergic and inflammatory diseases, cancer, cardiovascular and metabolic diseases, pain, hematologic conditions, infectious diseases and rare diseases.

Regeneron is accelerating and improving the traditional drug development process through our proprietary VelociSuite® technologies, such as VelocImmune®, which uses unique genetically humanized mice to produce optimized fully human antibodies and bispecific antibodies, and through ambitious research initiatives such as the Regeneron Genetics Center, which is conducting one of the largest genetics sequencing efforts in the world.

For more information, please visit www.Regeneron.com or follow @Regeneron on Twitter.

Sanofi is listed on EURONEXT: SAN and NASDAQ: SNY.

Dupilumab Development Program
Dupilumab is being jointly developed by Regeneron and Sanofi under a global collaboration agreement. To date, dupilumab has been studied across more than 60 clinical trials involving more than 10,000 patients with various chronic diseases driven in part by type 2 inflammation.

In addition to the currently approved indications, Regeneron and Sanofi are studying dupilumab in a broad range of diseases driven by type 2 inflammation or other allergic processes in Phase 3 trials, including prurigo nodularis, pediatric eosinophilic esophagitis, hand and foot atopic dermatitis, chronic inducible urticaria-cold, chronic spontaneous urticaria, chronic pruritis of unknown origin, chronic obstructive pulmonary disease with evidence of type 2 inflammation, chronic rhinosinusitis without nasal polyposis, allergic fungal rhinosinusitis, allergic bronchopulmonary aspergillosis and bullous pemphigoid. These potential uses of dupilumab are currently under clinical investigation, and the safety and efficacy in these conditions have not been fully evaluated by any regulatory authority.

U.S. Indications

DUPIXENT is a prescription medicine used:

to treat adults and children 6 months of age and older with moderate-to-severe atopic dermatitis (eczema) that is not well controlled with prescription therapies used on the skin (topical), or who cannot use topical therapies. DUPIXENT can be used with or without topical corticosteroids. It is not known if DUPIXENT is safe and effective in children with atopic dermatitis under 6 months of age.
with other asthma medicines for the maintenance treatment of moderate-to-severe eosinophilic or oral steroid dependent asthma in adults and children 6 years of age and older whose asthma is not controlled with their current asthma medicines. DUPIXENT helps prevent severe asthma attacks (exacerbations) and can improve your breathing. DUPIXENT may also help reduce the amount of oral corticosteroids you need while preventing severe asthma attacks and improving your breathing. DUPIXENT is not used to treat sudden breathing problems. It is not known if DUPIXENT is safe and effective in children with asthma under 6 years of age.
with other medicines for the maintenance treatment of chronic rhinosinusitis with nasal polyposis (CRSwNP) in adults whose disease is not controlled. It is not known if DUPIXENT is safe and effective in children with chronic rhinosinusitis with nasal polyposis under 18 years of age.
to treat adults and children 12 years of age and older, who weigh at least 88 pounds (40 kg), with eosinophilic esophagitis (EoE). It is not known if DUPIXENT is safe and effective in children with eosinophilic esophagitis under 12 years of age and who weigh at least 88 pounds (40 kg).

View original content:https://www.prnewswire.com/news-releases/late-breaking-dupixent-dupilumab-data-at-ers-2022-show-consistent-efficacy-and-safety-profile-for-up-to-two-years-in-children-aged-6-to-11-years-with-moderate-to-severe-asthma-301617551.html

SOURCE Regeneron Pharmaceuticals, Inc.

Sanofi/Regeneron Dupixent shows efficacy for up to 2 years in children with asthma

Sep. 05, 2022 6:18 AM ET

Sanofi (SNY), REGN

By: Ravikash, SA News Editor

Sanofi (NASDAQ:SNY) and Regeneron Pharmaceuticals (NASDAQ:REGN) said their medicine Dupixent showed efficacy and safety of up to two years in children aged six to 11 years with asthma.

https://seekingalpha.com/news/3880235-sanofiregeneron-dupixent-shows-efficacy-for-up-to-2-years-in-children-with-asthma

https://seekingalpha.com/symbol/SNY

https://seekingalpha.com/symbol/REGN

https://www.dupixent.com/

https://www.regeneron.com/

U.S. Indications DUPIXENT is a prescription medicine used: to treat adults and children 6 months of age and older with moderate-to-severe atopic dermatitis (eczema) that is not well controlled with prescription therapies used on the skin (topical), or who cannot use topical therapies. DUPIXENT can be used with or without topical corticosteroids. It is not known if DUPIXENT is safe and effective in children with atopic dermatitis under 6 months of age. with other asthma medicines for the maintenance treatment of moderate-to-severe eosinophilic or oral steroid dependent asthma in adults and children 6 years of age and older whose asthma is not controlled with their current asthma medicines. DUPIXENT helps prevent severe asthma attacks (exacerbations) and can improve your breathing. DUPIXENT may also help reduce the amount of oral corticosteroids you need while preventing severe asthma attacks and improving your breathing. DUPIXENT is not used to treat sudden breathing problems. It is not known if DUPIXENT is safe and effective in children with asthma under 6 years of age. with other medicines for the maintenance treatment of chronic rhinosinusitis with nasal polyposis (CRSwNP) in adults whose disease is not controlled. It is not known if DUPIXENT is safe and effective in children with chronic rhinosinusitis with nasal polyposis under 18 years of age. to treat adults and children 12 years of age and older, who weigh at least 88 pounds (40 kg), with eosinophilic esophagitis (EoE). It is not known if DUPIXENT is safe and effective in children with eosinophilic esophagitis under 12 years of age and who weigh at least 88 pounds (40 kg).

Imfinzi (durvalumab) plus chemotherapy

Forxiga (dapagliflozin) (known as Farxiga in the US)

Imfinzi plus chemotherapy approved in the US as the first immunotherapy regimen for patients with advanced biliary tract cancer

PUBLISHED5 September 2022

5 September 2022 07:00 BST

Approval based on TOPAZ-1 Phase III trial results, which showed Imfinzi
combination reduced risk of death by 20% vs. chemotherapy alone

AstraZeneca’s Imfinzi (durvalumab) has been approved in the US for the treatment of adult patients with locally advanced or metastatic biliary tract cancer (BTC) in combination with chemotherapy (gemcitabine plus cisplatin).

The approval by the Food and Drug Administration (FDA) was based on the results from the TOPAZ-1 Phase III trial. In an interim analysis of TOPAZ-1, Imfinzi plus chemotherapy reduced the risk of death by 20% versus chemotherapy alone (hazard ratio [HR] 0.80; 95% confidence interval [CI] 0.66-0.97; p=0.021). An estimated one in four (25%) patients treated with Imfinzi plus chemotherapy were still alive at two years compared to one in 10 (10%) treated with chemotherapy alone. Results were consistent across all prespecified subgroups, regardless of PD-L1 expression or tumour location.

BTC is a group of rare and aggressive cancers that occur in the bile ducts and gallbladder.1,2 Approximately 23,000 people in the US are diagnosed with BTC each year.1 These patients have a poor prognosis, with approximately 5% to 15% of patients with BTC surviving five years.3

Aiwu Ruth He, MD, PhD, Associate Professor of Medicine, Leader of the GI Cancer Program, Georgetown Lombardi Comprehensive Cancer Center, Medstar Georgetown University Hospital, Washington DC, and a lead investigator in the TOPAZ-1 Phase III trial, said: “This approval represents a major step forward for patients with advanced biliary tract cancer, who urgently need new, well-tolerated and effective treatment options after more than a decade of limited innovation. The combination of durvalumab and chemotherapy should become a new standard of care in this setting, having demonstrated significantly improved survival for these patients who have historically faced a poor prognosis.”

Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: “For the first time, patients in the US with advanced biliary tract cancer have an immunotherapy-based treatment option that meaningfully extends survival and is well-tolerated. This approval for Imfinzi and chemotherapy advances our ambition to challenge treatment expectations and transform care for patients with gastrointestinal cancers with high unmet need.”

Stacie Lindsey, CEO, Cholangiocarcinoma Foundation, said: “Patients have been waiting a long time for a new, first-line treatment option for biliary tract cancer. The Foundation congratulates AstraZeneca for engaging in rare cancer research, which impacts patients and families nationwide. We are especially grateful to the patients who participated in this trial making it possible for the broader rare disease community to benefit from this treatment.”

The TOPAZ-1 Phase III trial results were presented at the 2022 American Society of Clinical Oncology Gastrointestinal Cancers (ASCO GI) Symposium and published in the New England Journal of Medicine Evidence. Imfinzi plus chemotherapy was generally well tolerated and did not increase the discontinuation rate due to adverse events compared to chemotherapy alone.

In July 2022, Imfinzi plus chemotherapy was added to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) as a Category 1 preferred regimen as 1st-line therapy for locally advanced or metastatic BTC based on the data from TOPAZ-1.4

The US regulatory submission for TOPAZ-1 was reviewed under Project Orbis, which provides a framework for concurrent submission and review of oncology medicines among participating international partners. As part of Project Orbis, Imfinzi plus chemotherapy is also under regulatory review for the same indication by the Australian Therapeutic Goods Administration, the Brazilian Health Regulatory Agency (ANVISA), Health Canada, Israel’s Ministry of Health Pharmaceutical Administration, Singapore’s Health Sciences Authority, Switzerland’s Swissmedic and the UK’s Medicines and Healthcare products Regulatory Agency.

The approval was granted after securing Priority Review and Orphan Drug Designation for Imfinzi in the US in this setting. Regulatory applications are also currently under review in Europe, Japan and several other countries based on the TOPAZ-1 results.

TOPAZ-1
TOPAZ-1 is a randomised, double-blind, placebo controlled, multicentre, global Phase III trial of Imfinzi in combination with chemotherapy (gemcitabine plus cisplatin) versus placebo in combination with chemotherapy as a 1st-line treatment in 685 patients with unresectable advanced or metastatic BTC including intrahepatic and extrahepatic cholangiocarcinoma, and gallbladder cancer. Patients with ampullary carcinoma were excluded.

The primary endpoint is overall survival and key secondary endpoints included progression-free survival, objective response rate and safety. The trial was conducted in 105 centres across 17 countries including in the US, Europe, South America and several countries in Asia including South Korea, Thailand, Japan and China.

Imfinzi
Imfinzi (durvalumab) is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, countering the tumour’s immune-evading tactics and releasing the inhibition of immune responses.

In addition to the approval in BTC, Imfinzi is the only approved immunotherapy in the curative-intent setting of unresectable, Stage III non-small cell lung cancer (NSCLC) in patients whose disease has not progressed after chemoradiotherapy and is the global standard of care in this setting based on the PACIFIC Phase III trial.

Imfinzi is also approved in the US, EU, Japan, China and many other countries around the world for the treatment of extensive-stage small cell lung cancer (ES-SCLC) based on the CASPIAN Phase III trial. In 2021, updated results from the CASPIAN trial showed Imfinzi plus chemotherapy tripled patient survival at three years versus chemotherapy alone.

Imfinzi is also approved for previously treated patients with advanced bladder cancer in several countries.

Since the first approval in May 2017, more than 100,000 patients have been treated with Imfinzi.

As part of a broad development programme, Imfinzi is being tested as a single treatment and in combinations with other anti-cancer treatments for patients with SCLC, NSCLC, bladder cancer, several GI cancers, ovarian cancer, endometrial cancer, and other solid tumours.

AstraZeneca in GI cancers
AstraZeneca has a broad development programme for the treatment of GI cancers across several medicines and a variety of tumour types and stages of disease. In 2020, GI cancers collectively represented approximately 5.1 million new cancer cases leading to approximately 3.6 million deaths.6

Within this programme, the Company is committed to improving outcomes in gastric, liver, BTC, oesophageal, pancreatic, and colorectal cancers.

Imfinzi is being assessed in combinations in liver, BTC, oesophageal and gastric cancers in an extensive development programme spanning early to late-stage disease.

The Company aims to understand the potential of Enhertu (trastuzumab deruxtecan), a HER2-directed antibody drug conjugate, in the two most common GI cancers, colorectal and gastric cancers. Enhertu is jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.

Lynparza (olaparib) is a first-in-class PARP inhibitor with a broad and advanced clinical trial programme across multiple GI tumour types including pancreatic and colorectal cancers. Lynparza is developed and commercialised in collaboration with MSD (Merck & Co., Inc. inside the US and Canada).

AstraZeneca in immunotherapy
Immunotherapy is a therapeutic approach designed to stimulate the body’s immune system to attack tumours. The Company’s Immuno-Oncology (IO) portfolio is anchored in immunotherapies that have been designed to overcome evasion of the anti-tumour immune response. AstraZeneca is invested in using IO approaches that deliver long-term survival for new groups of patients across tumour types.

AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.

AstraZeneca's Imfinzi combo gets FDA approval for advanced biliary tract cancer

Sep. 05, 2022 5:37 AM ET

AstraZeneca PLC (AZN)

By: Ravikash, SA News Editor

The U.S. Food and Drug Administration (FDA) approved AstraZeneca's (NASDAQ:AZN) Imfinzi (durvalumab), in combination with chemotherapy (gemcitabine plus cisplatin) to treat adult patients with locally advanced or metastatic biliary tract cancer (BTC).
https://seekingalpha.com/news/3880230-astrazenecas-imfinzi-combo-gets-fda-approval-for-advanced-biliary-tract-cancer
https://seekingalpha.com/symbol/AZN
https://www.astrazeneca.com/
https://www.imfinzi.com/

Forxiga (dapagliflozin) (known as Farxiga in the US)

Forxiga approved in China for the treatment of chronic kidney disease in patients at risk of progression with and without
type-2 diabetes

PUBLISHED5 September 2022 5 September 2022 07:05 BST

Approval marks the first SGLT2 inhibitor approved in China for chronic kidney
disease in adult patients with and without type-2 diabetes

AstraZeneca’s Forxiga (dapagliflozin), a sodium-glucose cotransporter 2 (SGLT2) inhibitor, has been approved in China to reduce the risk of sustained estimated glomerular filtration rate (eGFR) decline, end-stage kidney disease (ESKD), cardiovascular (CV) death and hospitalisation for heart failure (hHF) in adults with chronic kidney disease (CKD) at risk of progression with and without type-2 diabetes (T2D).

The approval by China’s National Medical Products Administration (NMPA) is based on positive results from the DAPA-CKD Phase III trial1.

CKD is a serious, progressive condition defined by decreased kidney function and is often associated with an increased risk of heart disease or stroke2-4. The condition affects 850 million people worldwide5. However, diagnosis rates remain low and up to 90% of patients are unaware they have the disease4.

Member of the DAPA-CKD Executive Committee, Fan Fan Hou, Southern Medical University, Guangzhou, China, said: “With unprecedented results of DAPA-CKD, dapagliflozin becomes the first SGLT2 inhibitor approved in China for the treatment of chronic kidney disease. This transformational milestone brings great hope to the 120 million subjects suffering from chronic kidney disease in China.”

Sir Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca said: “In addition to AstraZeneca’s commitment to drive increased awareness, prevention and earlier diagnoses, this approval marks another important step forward in our ambition to stop, reverse and ultimately cure chronic kidney disease globally. We are thrilled at the opportunity to bring Forxiga to millions of patients across the country and improve patient outcomes.”

The DAPA-CKD Phase III trial demonstrated that Forxiga, on top of standard-of-care (SoC) treatment with an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker, reduced the relative risk of worsening of renal function, onset of ESKD, or risk of CV or renal death by 39%, the primary composite endpoint, compared to placebo (absolute risk reduction [ARR]=5.3%, p<0.0001) in patients with CKD Stages 2-4 and elevated urinary albumin excretion. Forxiga also significantly reduced the relative risk of death from any cause by 31% (ARR=2.1%, p=0.0035) compared to placebo6. The safety and tolerability of Forxiga were consistent with the well-established safety profile of the medicine.

Forxiga (known as Farxiga in the US) is now approved in 100 countries around the world including the US, the European Union and Japan for the treatment of CKD in adults with and without T2D.

DAPA-CKD
DAPA-CKD was an international, multi-centre, randomised, double-blinded Phase III trial in 4,304 patients designed to evaluate the efficacy of Forxiga 10mg, compared with placebo, in patients with CKD Stage 2-4 and elevated urinary albumin excretion, with and without T2D. Forxiga was given once daily in addition to SoC. The primary composite endpoint was worsening of renal function or risk of death (defined as a composite of an eGFR decline ≥50%, onset of ESKD or death from CV or renal cause). The secondary endpoints included the time to first occurrence of the renal composite (sustained ≥50% eGFR decline, ESKD or renal death), the composite of CV death or hospitalisation for HF (hHF), and death from any cause. The trial was conducted in 21 countries1. Detailed results from the trial were published in The New England Journal of Medicine1.

Forxiga
Forxiga (dapagliflozin) is a first-in-class, oral, once-daily SGLT2 inhibitor. Research has shown Forxiga’s efficacy in preventing and delaying cardiorenal disease, while also protecting the organs – important findings given the underlying links between the heart, kidneys and pancreas1,10,11. Damage to one of these organs can cause the other organs to fail, contributing to leading causes of death worldwide, including T2D, HF and CKD12-15.

Forxiga is approved as an adjunct to diet and exercise to improve glycaemic control in adults with T2D and in T2D to reduce the risk of hHF or CV death when added to SoC based on the findings of the DECLARE-TIMI 58 Phase III CV outcomes trial11. Forxiga is also approved for the treatment of HFrEF and the treatment of CKD based on the findings of the DAPA-HF and DAPA-CKD Phase III trials6,10.

DapaCare is a robust programme of clinical trials to evaluate the potential CV, renal and organ protection benefits of Forxiga. It includes more than 35 completed and ongoing Phase IIb/III trials in more than 35,000 patients, as well as more than 2.5 million patient-years’ experience. Forxiga is currently being tested in patients without T2D following an acute myocardial infarction (MI) or heart attack in the DAPA-MI Phase III trial - a first of its kind, indication-seeking registry-based randomised controlled trial16.

https://www.farxiga.com/

AstraZeneca in CVRM
Cardiovascular, Renal and Metabolism (CVRM), part of BioPharmaceuticals, forms one of AstraZeneca’s main disease areas and is a key growth driver for the Company. By following the science to understand more clearly the underlying links between the heart, kidneys and pancreas, AstraZeneca is investing in a portfolio of medicines for organ protection and improving outcomes by slowing disease progression, reducing risks and tackling co-morbidities. The Company’s ambition is to modify or halt the natural course of CVRM diseases and potentially regenerate organs and restore function, by continuing to deliver transformative science that improves treatment practices and CV health for millions of patients worldwide.

AstraZeneca's Forxiga gets approval in China for kidney disease with/without type-2 diabetes

Sep. 05, 2022 6:28 AM ET

AstraZeneca PLC (AZN)

By: Ravikash, SA News Editor

AstraZeneca's (NASDAQ:AZN) Forxiga was approved in China to reduce the risk of sustained estimated glomerular filtration rate ((eGFR)) decline, end-stage kidney disease (ESKD), cardiovascular (CV) death and hospitalization for heart failure (hHF) in adults with chronic kidney disease (CKD) at risk of progression with and without type-2 diabetes (T2D).
https://seekingalpha.com/news/3880236-astrazenecas-forxiga-gets-approval-in-china-for-kidney-disease-withwithout-type-2-diabetes
https://seekingalpha.com/symbol/AZN
https://www.farxiga.com/
https://www.ema.europa.eu/en/medicines/human/EPAR/forxiga

What is FARXIGA? FARXIGA is a prescription medicine used to: improve blood sugar control along with diet and exercise in adults with type 2 diabetes reduce the risk of hospitalization for heart failure in adults with type 2 diabetes and known cardiovascular disease or multiple cardiovascular risk factors reduce the risk of cardiovascular death and hospitalization for heart failure in adults with symptomatic heart failure (when the heart is weak and cannot pump enough blood to the rest of your body) reduce the risk of further worsening of your kidney disease, end-stage kidney disease, death due to cardiovascular disease, and hospitalization for heart failure in adults with chronic kidney disease FARXIGA is not for people with type 1 diabetes. FARXIGA may increase the risk of diabetic ketoacidosis (increased ketones in your blood or urine) in people with type 1 diabetes. FARXIGA is not for use to improve blood sugar (glucose) control in adults with type 2 diabetes who have moderate to severe kidney problems, because it may not work. FARXIGA is not for people with certain genetic forms of polycystic kidney disease, or who are taking or have recently received immunosuppressive therapy to treat kidney disease. FARXIGA is not expected to wo

TRODELVY® (sacituzumab govitecan-hziy)

September 04, 2022

New TROPiCS-02 Data in HR+/HER2- Metastatic Breast Cancer Patients Demonstrates Progression-Free Survival Benefit of Trodelvy® Regardless of Their HER2 Status

-- Progression-Free Survival Efficacy of Trodelvy Consistent with That Observed in the TROPiCS-02 Intention-to-Treat Population --

-- Results Presented at ESMO 2022 Highlight Trodelvy as a Potential Treatment Option in HR+/HER2-Low and IHC0 Status Metastatic Breast Cancer --

FOSTER CITY, Calif.--(BUSINESS WIRE)-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced new data from a post hoc subgroup analysis from the Phase 3 TROPiCS-02 study evaluating Trodelvy® (sacituzumab govitecan-hziy) versus comparator chemotherapies (physicians’ choice of chemotherapy, TPC) in patients with HR+/HER2- metastatic breast cancer who progressed on endocrine-based therapies and at least two chemotherapies. The analysis examined progression-free survival (PFS) in the intention-to-treat population by HER2-immunohistochemistry (IHC) status, and the results demonstrated that Trodelvy improved median PFS vs. TPC in both HER2-low (IHC1+ and IHC2+/ISH-negative) and IHC0 groups.

Detailed findings will be presented at a mini-oral session (Abstract #1362) during the European Society for Medical Oncology (ESMO) Congress 2022 in the Évry Auditorium, Paris Expo Porte de Versailles, on September 10.

“These data demonstrate Trodelvy’s efficacy across HER2-low and IHC0 status in pre-treated metastatic breast cancer patients in the TROPiCS-02 trial,” said Professor Peter Schmid, Professor of Cancer Medicine; Centre Lead, Centre of Experimental Cancer Medicine; Director, Barts Breast Cancer Centre. “Once patients have developed resistance to endocrine-based therapies, their prognosis is extremely poor. The results highlight the potential for Trodelvy as a treatment option for people living with pre-treated HR+/HER2- metastatic breast cancer, regardless of their HER2-negative status.”

“These results show Trodelvy improved progression-free survival regardless of HER2 status in this pre-treated patient population and reinforce the strength of clinical activity in a population where need is highest,” said Bill Grossman, MD, PhD, Senior Vice President, Therapeutic Area Head, Gilead Oncology. “Trodelvy is already transforming the standard of care in second-line metastatic triple-negative breast cancer, and we’re excited about its potential in other breast cancers where there is significant need for new treatment options.”

In the study, HER2 negativity was defined per American Society of Clinical Oncology (ASCO) and the College of American Pathologists (CAP) criteria as immunohistochemistry (IHC) score of 0, IHC 1+ or IHC 2+ with a negative in-situ hybridization (ISH) test.

Sacituzumab govitecan is currently included in the National Comprehensive Cancer Network® (NCCN®) Clinical Practice Guidelines in Oncology (NCCN Guidelines®)i. This includes a Category 1 recommendation for use in adult patients with second-line metastatic triple-negative breast cancer (defined as those who received at least two prior therapies, with at least one line for metastatic disease). It also has a Category 2A preferred recommendation for investigational use in HR+/HER2- advanced breast cancer after prior treatment including endocrine therapy, a CDK4/6 inhibitor and at least two lines of chemotherapy.

Trodelvy has a Boxed Warning for severe or life-threatening neutropenia and severe diarrhea; please see below for additional Important Safety Information.

About the TROPiCS-02 Study

The TROPiCS-02 study is a global, multicenter, open-label, Phase 3 study, randomized 1:1 to evaluate Trodelvy versus physicians’ choice of chemotherapy (eribulin, capecitabine, gemcitabine, or vinorelbine) in 543 patients with HR+/HER2- metastatic breast cancer who were previously treated with endocrine therapy, CDK4/6 inhibitors and two to four lines of chemotherapy for metastatic disease. The primary endpoint is progression-free survival per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) as assessed by blinded independent central review (BICR) for participants treated with Trodelvy compared to those treated with chemotherapy. Secondary endpoints include overall survival, overall response rate, clinical benefit rate and duration of response, as well as assessment of safety and tolerability and quality of life measures. More information about TROPiCS-02 is available at https://clinicaltrials.gov/ct2/show/NCT03901339.

About Trodelvy

U.S. Indications for Trodelvy

In the United States, Trodelvy is indicated for the treatment of:

Adult patients with unresectable locally advanced or metastatic TNBC who have received two or more prior systemic therapies, at least one of them for metastatic disease.
Adult patients with locally advanced or metastatic UC who have previously received a platinum-containing chemotherapy and either programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Please see full Prescribing Information , including BOXED WARNING.

https://www.trodelvy.com/

About Gilead Sciences

U.S. Prescribing Information for Trodelvy including BOXED WARNING, is available at www.gilead.com.

Trodelvy, Gilead and the Gilead logo are trademarks of Gilead Sciences, Inc., or its related companies.

For more information about Gilead, please visit the company’s website at www.gilead.com, follow Gilead on Twitter (@GileadSciences) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.

i Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer Version 4.2022. © National Comprehensive Cancer Network, Inc. 2022. All rights reserved. Accessed August 2022. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

View source version on businesswire.com: https://www.businesswire.com/news/home/20220902005309/en/

Source: Gilead Sciences, Inc.

Gilead Trodelvy shows benefit in breast cancer patients regardless of HER2 mutation in trial

Sep. 05, 2022 6:44 AM ET

Gilead Sciences, Inc. (GILD)

By: Ravikash, SA News Editor7 Comments

Gilead Sciences (NASDAQ:GILD) said Trodelvy showed progression-free survival (PFS) benefit in patients with breast cancer patients regardless of the HER2 mutation status.

https://seekingalpha.com/news/3880237-gilead-trodelvy-shows-benefit-in-breast-cancer-patients-regardless-of-her2-mutation-in-trial

https://seekingalpha.com/symbol/GILD

https://www.trodelvy.com/

FARXIGA® (dapagliflozin)

TRODELVY® (sacituzumab govitecan-hziy)

New data show FARXIGA significantly lowers the risk of cardiovascular death in patients with heart failure

PUBLISHED27 August 2022

Pre-specified pooled analysis from Phase III trials demonstrated reduction in CV death by 14% and reduction in death from any cause by 10% in patients with heart failure irrespective of ejection fraction

First heart failure medication to demonstrate mortality benefit across the full ejection fraction range

Results being presented at the European Society of Cardiology annual meeting and simultaneously published in Nature Medicine

Today, new results from a pre-specified, patient level, pooled analysis from the Phase III DAPA-HF and DELIVER trials demonstrated mortality benefit of FARXIGA® (dapagliflozin), compared to placebo, in patients with heart failure (HF). These results were presented at the European Society of Cardiology Congress 2022 in Barcelona, Spain and simultaneously published in Nature Medicine.1 The reduction in risk of cardiovascular (CV) death was consistent across pre-specified subgroups and is the first analysis to demonstrate a mortality benefit with an HF medication in patients with HF across the left ventricular ejection fraction (LVEF) range.

The analysis showed that FARXIGA reduced the risk of CV death by 14% (p=0.01, absolute risk reduction [ARR] 1.5%) over the median follow-up of 22 months, death from any cause by 10% (p=0.03, ARR 1.5%), total (first and repeat) hospitalization for HF (hHF) by 29% (p < 0.001, ARR 6%), and the composite of death from CV causes, myocardial infarction, or stroke by 10% (p=0.045, ARR 1.3%), in patients with HF irrespective of LVEF.1

Prof. John McMurray, Professor of Medical Cardiology and Deputy Director of the Institute of Cardiovascular and Medical Sciences at the University of Glasgow, UK, said: “In this patient-level meta-analysis including over 11,000 patients with heart failure across the full range of ejection fraction, dapagliflozin reduced the risk of both cardiovascular death and heart failure hospitalization. These results underpin the valuable role dapagliflozin can play in clinical practice, as we can initiate treatment right away while waiting for ejection fraction to be measured.”

Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca, said:

“Heart failure remains one of the leading causes of death worldwide with high unmet need for some 64 million people. This analysis demonstrates FARXIGA’s ability to treat patients across the full left ventricular ejection fraction spectrum and reduce the risk of cardiovascular death.”

The DAPA-HF and DELIVER Phase III trials were randomized and double-blind, comparing FARXIGA to placebo. Each trial enrolled patients with a diagnosis of HF, functional limitation, and elevated natriuretic peptides. The principal difference between the two trials was that patients with an LVEF of 40% or less were randomized in DAPA-HF and those with a LVEF greater than 40% in DELIVER.2,3 The studies included 11,007 individuals with HF across 20 countries in each trial.

INDICATIONS AND LIMITATIONS OF USE for FARXIGA® (dapagliflozin)

FARXIGA is indicated:

as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus
to reduce the risk of hospitalization for heart failure in adults with type 2 diabetes mellitus and either established cardiovascular (CV) disease or multiple CV risk factors
to reduce the risk of cardiovascular death and hospitalization for heart failure in adults with heart failure (NYHA class II-IV) with reduced ejection fraction
to reduce the risk of sustained eGFR decline, end‑stage kidney disease, cardiovascular death, and hospitalization for heart failure in adults with chronic kidney disease at risk of progression

FARXIGA is not recommended for patients with type 1 diabetes mellitus. It may increase the risk of diabetic ketoacidosis in these patients.

FARXIGA is not recommended for use to improve glycemic control in adults with type 2 diabetes mellitus with an eGFR less than 45 mL/min/1.73 m2. FARXIGA is likely to be ineffective in this setting based upon its mechanism of action.

FARXIGA is not recommended for the treatment of chronic kidney disease in patients with polycystic kidney disease or patients requiring or with a recent history of immunosuppressive therapy for kidney disease. FARXIGA is not expected to be effective in these populations.

DOSING

To improve glycemic control, the recommended starting dose is 5 mg orally once daily. Dose can be increased to 10 mg orally once daily for additional glycemic control.

For all other indications, the recommended dose is 10 mg orally once daily.

https://www.farxiga.com/

DAPA-HF
DAPA-HF (Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure) was an international, multi-centre, parallel-group, randomized, double-blinded Phase III trial in 4,744 patients with HFrEF, with and without type 2 diabetes (T2D), designed to evaluate the effect of FARXIGA 10mg, compared with placebo, given once daily in addition to standard of care (SoC) consisting of an angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin receptor blocker (ARB). The primary composite endpoint was time to the first occurrence of a worsening HF event (hospitalization or equivalent event, i.e., an urgent HF visit), or CV death. The median duration of follow-up was 18.2 months.3

The secondary endpoint included the total number of hHF (including repeat admissions) and CV deaths, change from baseline to 8 months in the total symptom score on the Kansas City Cardiomyopathy Questionnaire (KCCQ).3

DELIVER
DELIVER was an international, randomized, double-blind, parallel-group, placebo-controlled, event-driven Phase III trial designed to evaluate the efficacy of FARXIGA, compared with placebo, in the treatment of HF patients with LVEF greater than 40%, with or without T2D. FARXIGA was given once daily in addition to background therapy (regional SoC for all comorbidities, including diabetes and hypertension, with the exception of concomitant use of a sodium-glucose cotransporter 2 (SGLT2) inhibitor).2 DELIVER is the largest clinical trial to date in HF patients with LVEF above 40%, with 6,263 randomized patients.2

The primary endpoint was the time to first occurrence of CV death, hHF or an urgent HF visit. The secondary endpoint includes the total number of HF events (hHF or urgent HF visit) and CV death, change from baseline in the total symptom score of the KCCQ at eight months, time to the occurrence of CV death and time to the occurrence of death from any cause.2

AstraZeneca in CVRM

Cardiovascular, Renal and Metabolism (CVRM), part of BioPharmaceuticals, forms one of AstraZeneca’s main disease areas and is a key growth driver for the Company. By following the science to understand more clearly the underlying links between the heart, kidneys and pancreas, AstraZeneca is investing in a portfolio of medicines for organ protection and improving outcomes by slowing disease progression, reducing risks and tackling co-morbidities. The Company’s ambition is to modify or halt the natural course of CVRM diseases and potentially regenerate organs and restore function, by continuing to deliver transformative science that improves treatment practices and CV health for millions of patients worldwide.

About AstraZeneca

AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialization of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information, please visit www.astrazeneca-us.com and follow us on Twitter @AstraZenecaUS.

AstraZeneca posts late-stage data to show potential of diabetes drug in heart failure

Aug. 29, 2022 5:16 AM ET AstraZeneca PLC (AZN)

By: Dulan Lokuwithana, SA News Editor

Disclosing data from a Phase 3 trial, AstraZeneca (NASDAQ:AZN) announced that its blockbuster diabetes therapy Farxiga (dapagliflozin) improved clinical outcomes in certain patients with heart failure (HF). The data were presented at the European Society of Cardiology Congress 2022 in Spain.

https://seekingalpha.com/news/3877314-astrazeneca-posts-data-to-show-potential-of-diabetes-drug-in-heart-failure

https://seekingalpha.com/symbol/AZN

https://www.farxiga.com/

Lynparza (olaparib)

TRODELVY® (sacituzumab govitecan-hziy)

IMBRUVICA® (ibrutinib)

Lynparza approved in Japan as adjuvant treatment for patients with BRCA-mutated HER2-negative high-risk early breast cancer

PUBLISHED25 August 2022

25 August 2022 07:00 BST

First and only approved medicine targeting
BRCA mutations in early breast cancer

AstraZeneca and MSD’s Lynparza (olaparib) has been approved in Japan for the adjuvant treatment of patients with BRCA-mutated (BRCAm), HER2-negative early breast cancer at high risk of recurrence.

This approval by the Japanese Ministry of Health, Labour, and Welfare was based on results from the OlympiA Phase III trial published in The New England Journal of Medicine in June 2021.1 In the trial, Lynparza demonstrated a statistically significant and clinically meaningful improvement in invasive disease-free survival (iDFS), reducing the risk of invasive breast cancer recurrences, new cancers, or death by 42% versus placebo (based on a hazard ratio [HR] of 0.58; 99.5% confidence interval [CI] 0.41-0.82; p<0.0001).

Lynparza also demonstrated a statistically significant and clinically meaningful improvement in overall survival, reducing the risk of death by 32% versus placebo (based on an HR of 0.68; 98.5% CI 0.47-0.97; p=0.009). The safety and tolerability profile of Lynparza in this trial was in line with that observed in prior clinical trials.

Breast cancer is the most diagnosed cancer worldwide with an estimated 2.3 million patients diagnosed in 2020.2 In Japan, an estimated 95,000 people will be diagnosed with breast cancer in 2022, and over 15,000 will die from the disease.3,4 Out of the approximately 80% of patients with HER2-negative breast cancer, about 11% have BRCA mutations.5,6

Professor Andrew Tutt, Global Chair of the OlympiA Phase III trial and Professor of Oncology at The Institute of Cancer Research, London, and King’s College London, said: “Today’s approval marks a new era of care for patients in Japan. For patients with high-risk early-stage breast cancer, including those with germline BRCA mutations, recurrence rates remain unacceptably high, with more than one in four of these patients seeing their cancer return following surgery and systemic treatment. Today’s approval offers eligible patients in Japan an effective and targeted treatment that improves survival and helps to prevent cancer recurrence.”

Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: “Today’s approval marks a significant leap forward for breast cancer patients in Japan, where it is the most commonly diagnosed cancer among women. Patients with BRCA mutations have high rates of disease recurrence and lower survival, and Lynparza has been shown to significantly reduce both the risk of recurrence and death. We hope this approval sets a new, much-needed standard of care for these early breast cancer patients in Japan.”

Dr Eliav Barr, Senior Vice President, Head of Global Clinical Development and Chief Medical Officer, MSD Research Laboratories, said: “With this approval, Lynparza becomes the first and only PARP inhibitor available for patients with BRCA-mutated HER2-negative early breast cancer in Japan. This further reinforces the critical need to conduct BRCA testing at the point of diagnosis so that all eligible patients can be identified.”

In March 2022, Lynparza was approved in the US for the treatment of germline BRCAm (gBRCAm), HER2-negative high-risk early breast cancer, followed by approval in the EU in August 2022 based on the results of the OlympiA Phase III trial. Lynparza is also approved in the US, EU, Japan, and many other countries for the treatment of patients with gBRCAm, HER2-negative, metastatic breast cancer previously treated with chemotherapy based on results from the OlympiAD Phase III trial. In the EU, this indication also includes patients with locally advanced breast cancer.

OlympiA
OlympiA is a Phase III, double-blind, parallel group, placebo-controlled, multicentre trial testing the efficacy and safety of Lynparza tablets versus placebo as adjuvant treatment in patients with gBRCAm, high-risk HER2-negative early breast cancer, who have completed definitive local treatment and neoadjuvant or adjuvant chemotherapy.15

The primary endpoint of the trial was iDFS defined as time from randomisation to date of first locoregional or distant recurrence or new cancer or death from any cause.1

The OlympiA Phase III trial is led by the Breast International Group in partnership with the Frontier Science & Technology Research Foundation, NRG Oncology, the US National Cancer Institute, AstraZeneca and MSD. The trial is sponsored by NRG Oncology in the US and by AstraZeneca outside the US.

BRCA
BRCA1 and BRCA2 are human genes that produce proteins responsible for repairing damaged DNA and play an important role maintaining the genetic stability of cells.11 When either of these genes is mutated or altered such that its protein product either is not made or does not function correctly, DNA damage may not be repaired properly, and cells become unstable. As a result, cells are more likely to develop additional alterations that can lead to cancer. Cancers with BRCA mutations are more likely to be sensitive to PARP inhibitors including Lynparza.16-19

Lynparza is currently approved in a number of countries across PARP-dependent tumour types with defects and dependencies in the DDR pathway including maintenance treatment of platinum-sensitive relapsed ovarian cancer and as both monotherapy and in combination with bevacizumab for the 1st-line maintenance treatment of BRCA-mutated (BRCAm) and homologous recombination repair deficient (HRD)-positive advanced ovarian cancer, respectively; for gBRCAm, HER2-negative metastatic breast cancer (in the EU and Japan this includes locally advanced breast cancer); for gBRCAm, HER2-negative high-risk early breast cancer (in the EU and US); for gBRCAm metastatic pancreatic cancer; and HRR gene-mutated metastatic castration-resistant prostate cancer (BRCAm only in the EU and Japan).

https://www.lynparza.com/

AstraZeneca in breast cancer
Driven by a growing understanding of breast cancer biology, AstraZeneca is starting to challenge and redefine the current clinical paradigm for how breast cancer is classified and treated, to deliver even more effective treatments to patients in need – with the bold ambition to one day eliminate breast cancer as a cause of death.

AstraZeneca has a comprehensive portfolio of approved and promising compounds in development that leverage different mechanisms of action to address the biologically diverse breast cancer tumour environment.

AstraZeneca aims to continue to transform outcomes for HR-positive breast cancer with foundational medicines Faslodex and Zoladex and the next-generation oral selective oestrogen receptor degrader (SERD) and potential new medicine camizestrant.

The PARP inhibitor, Lynparza, is an approved targeted treatment option for early and metastatic breast cancer patients with an inherited BRCA mutation. AstraZeneca with MSD continue to research Lynparza in breast cancer patients with an inherited BRCA mutation.

Building on the initial approvals of Enhertu, a HER2-directed antibody drug conjugate (ADC), in previously treated HER2-positive metastatic breast cancer, AstraZeneca and Daiichi Sankyo are exploring its potential in earlier lines of treatment and in new breast cancer settings. Enhertu has received approval in the US in previously treated HER2-low metastatic breast cancer.

To bring much needed treatment options to patients with triple-negative breast cancer, an aggressive form of breast cancer, AstraZeneca is testing immunotherapy Imfinzi in combination with other oncology medicines, including Lynparza and Enhertu, evaluating the potential of AKT kinase inhibitor, capivasertib, in combination with chemotherapy, and collaborating with Daiichi Sankyo to explore the potential of TROP2-directed ADC, datopotamab deruxtecan.

AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.

AstraZeneca/Merck's Lynparza gets approval in Japan for early breast cancer subtype

Aug. 25, 2022 4:23 AM ET

AstraZeneca PLC (AZN), MRK

By: Ravikash, SA News Editor

The Japanese Ministry of Health, Labour, and Welfare approved AstraZeneca (NASDAQ:AZN) and Merck's (NYSE:MRK) Lynparza as adjuvant therapy for patients with BRCA-mutated (BRCAm), HER2-negative early breast cancer at high risk of recurrence.

WHAT IS LYNPARZA? LYNPARZA is a prescription medicine used to treat adults who have: advanced ovarian cancer, fallopian tube cancer, or primary peritoneal cancer with a certain type of inherited (germline) or acquired (somatic) abnormal BRCA gene. LYNPARZA is used alone as maintenance treatment after the cancer has responded to your first treatment with platinum-based chemotherapy. Your healthcare provider will perform a test to make sure that LYNPARZA is right for you advanced ovarian cancer, fallopian tube cancer, or primary peritoneal cancer with a certain type of abnormal BRCA gene or a positive laboratory tumor test for genomic instability called HRD. LYNPARZA is used in combination with another anti-cancer medicine, bevacizumab, as maintenance treatment after the cancer has responded to your first treatment with platinum-based chemotherapy. Your healthcare provider will perform a test to make sure that LYNPARZA is right for you ovarian cancer, fallopian tube cancer, or primary peritoneal cancer, as maintenance treatment, when the cancer has come back. LYNPARZA is used after the cancer has responded to treatment with platinum-based chemotherapy advanced ovarian cancer with a certain type of abnormal inherited BRCA gene, and have received treatment with 3 or more prior types of chemotherapy medicines. Your healthcare provider will perform a test to make sure that LYNPARZA is right for you human epidermal growth factor receptor 2 (HER2)-negative early breast cancer with a certain type of inherited (germline) abnormal BRCA gene. LYNPARZA is given after surgery (treatment after surgery is called adjuvant therapy). You should have received chemotherapy medicines before or after surgery to remove the tumor. Your healthcare provider will perform a test to make sure that LYNPARZA is right for you a certain type of abnormal inherited BRCA gene, human epidermal growth factor receptor 2 (HER2)-negative breast cancer that has spread to other parts of the body (metastatic). You should have received chemotherapy medicines, either before or after your cancer has spread. If you have hormone receptor (HR)-positive disease, you should have been treated with hormonal therapy. Your healthcare provider will perform a test to make sure that LYNPARZA is right for you metastatic pancreatic cancer with a certain type of abnormal inherited BRCA gene. LYNPARZA is used as a maintenance treatment after your cancer has not progressed on at least 16 weeks of treatment with platinum-based chemotherapy. Your healthcare provider will perform a test to make sure LYNPARZA is right for you prostate cancer with certain inherited or acquired abnormal genes called homologous recombination repair (HRR genes). LYNPARZA is used when the cancer has spread to other parts of the body (metastatic), and no longer responds to a medical or surgical treatment that lowers testosterone, and has progressed after treatment with enzalutamide or abiraterone. Your healthcare provider will perform a test to make sure LYNPARZA is right for you It is not known if LYNPARZA is safe and effective in children.

IMBRUVICA® (ibrutinib)

LYNPARZA® (olaparib) in combination with abiraterone

IMBRUVICA® (ibrutinib)

U.S. FDA Approves IMBRUVICA® (ibrutinib) as First and Only BTKi Treatment for Pediatric Patients with Chronic Graft-Versus-Host DiseaseIMBRUVICA® is now the only BTKi with 12 FDA approvals across seven indications, including five hematologic cancers and cGVHD

August 24, 2022 (HORSHAM, PA) –

The Janssen Pharmaceutical Companies of Johnson & Johnson announced today that the U.S. Food and Drug Administration (FDA) has approved IMBRUVICA® (ibrutinib) for the treatment of pediatric patients one year and older with chronic graft-versus-host disease (cGVHD) after failure of one or more lines of systemic therapy. This milestone marks the first pediatric indication for IMBRUVICA® and the introduction of a new oral suspension formulation for patients ages one to less than 12. IMBRUVICA® is now the first FDA-approved therapy for these younger patients who previously had no approved treatment options for this life-threatening disease.

Chronic graft-versus-host disease is a life-threatening complication that can occur after a stem cell or bone marrow transplant when newly transplanted donor cells attack the transplant recipient's body.[1] Symptoms may include skin rash, mouth sores, dry eyes, liver inflammation, development of scar tissue in the skin and joints, and damage to the lungs.[1] Among children who undergo allogeneic transplants, 52-65 percent will develop cGVHD.[2]

“Imagine going through a transplant and then being told you have a moderate to severe chronic disease that can sometimes also be life-threatening,” said Dr. Paul A. Carpenter, attending physician at Seattle Children's Hospital and a study principal investigator.† “If these children were between one and 12 and didn’t respond to steroid treatment, we didn’t have any rigorously studied treatment options — until now. The iMAGINE trial showed encouraging safety results and sustained response rates in children, and the new IMBRUVICA oral suspension formulation helps address challenges children may have with swallowing capsules or tablets.”

“It’s heartbreaking for parents to watch their child struggle with the debilitating effects of cGVHD, especially since there are so few treatment options,” said Susan Stewart, Executive Director of BMT InfoNet,^ a non-profit organization dedicated to providing patients and their loved ones with emotional support and high quality, easy-to-understand information about blood stem cell transplants. “The FDA approval of IMBRUVICA puts another weapon in their arsenal and has the potential to truly make a difference for those who are faced with this challenging disease.”

The new indication is based on results from the Phase 1/2 iMAGINE study, which showed an overall response rate (ORR) through week 25 of 60 percent (Confidence Interval [CI] 95 percent; 44-74) in patients median age 13 years (range, one to 19 years) (n=47) with relapsed/refractory (R/R) moderate to severe cGVHD. Safety was consistent with the established profile for IMBRUVICA®, with observed adverse events (AEs) in pediatric patients being consistent with those observed in adult patients with moderate to severe cGVHD. IMBRUVICA® was approved to treat adults with cGVHD after failure of one or more lines of systemic therapy in 2017. Because of its unique kinase profile (e.g., inhibiting both BTK and interleukin-2-inducible T-cell kinase [ITK]), IMBRUVICA® has the potential to provide a clinical benefit for cGVHD.[3]

“The pediatric cGVHD community is a prime example of an underserved patient population with high unmet medical needs for whom Janssen is committed to developing life-saving therapies,” said Craig Tendler, M.D., Global Head of Late Development, Diagnostics & Medical Affairs, Hematology & Oncology Janssen Research & Development, LLC. “cGVHD has life-threatening implications for children, and we are deeply proud of the opportunity to make an impact for these young patients with IMBRUVICA and their families.”

About the iMAGINE Study
iMAGINE (PCYC-1146-IM) is an open-label, multi-center, single-arm trial of IMBRUVICA® for the treatment of pediatric and young adult patients aged one year to less than 22 years with moderate or severe cGVHD as defined by NIH Consensus Criteria. Primary endpoints included pharmacokinetics (PK) and safety, and secondary endpoints included ORR (complete response [CR]/partial response [PR]) per 2014 NIH criteria, overall survival, and duration of response (DOR). The study included 47 patients who required additional therapy after failure of one or more prior lines of systemic therapy. Patients aged 12 years and older were treated with IMBRUVICA® 420 mg orally once daily, and patients aged one year to less than 12 years were treated with IMBRUVICA® 240 mg/m2 orally once daily. The efficacy of IMBRUVICA® was established based on ORR through Week 25.

About IMBRUVICA®
IMBRUVICA® (ibrutinib) is a once-daily oral medication that is jointly developed and commercialized by Janssen Biotech, Inc. and Pharmacyclics LLC, an AbbVie company. IMBRUVICA® blocks the Bruton's tyrosine kinase (BTK) protein, which is needed by normal and abnormal B cells, including specific cancer cells, to multiply and spread. By blocking BTK, IMBRUVICA® may help move abnormal B cells out of their nourishing environments and inhibits their proliferation.[4],[5],[6]

IMBRUVICA® is approved in more than 100 countries and has been used to treat more than 250,000 patients worldwide. There are more than 50 company-sponsored clinical trials, including 18 Phase 3 studies, more than 11 years evaluating the efficacy and safety of IMBRUVICA®.

IMBRUVICA® was first approved by the U.S. Food and Drug Administration (FDA) in November 2013, and today is indicated for adult patients in six disease areas, including five hematologic cancers. These include indications to treat adults with chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL) with or without 17p deletion (del17p), and adults with Waldenström’s macroglobulinemia (WM), and adult patients with previously treated mantle cell lymphoma (MCL)*, as well as to treat adult patients with previously treated marginal zone lymphoma (MZL) who require systemic therapy and have received at least one prior anti-CD20-based therapy*, and adult and pediatric patients aged one year and older with previously treated chronic graft-versus-host disease (cGVHD) after failure of one or more lines of systemic therapy.[7]

*Accelerated approval was granted for MCL and MZL based on overall response rate. Continued approval for MCL and MZL may be contingent upon verification and description of clinical benefit in confirmatory trials.

Since 2019, the National Comprehensive Cancer Network® (NCCN®), recommends ibrutinib (IMBRUVICA®) as a preferred regimen for the initial treatment of CLL/SLL and has Category 1 treatment status for treatment-naïve patients without deletion 17p/TP53 mutation and as a preferred treatment for treatment-naïve patients with deletion 17p/TP53 mutation. The NCCN Guidelines® also recommend IMBRUVICA®, with or without rituximab, as a preferred regimen for the treatment of relapsed/refractory MCL, as a Category 1 preferred regimen for both untreated and previously treated WM patients, and as a preferred regimen for relapsed/refractory MZL.[8]

For more information, visit www.IMBRUVICA.com.

Please see full Prescribing Information.

About the Janssen Pharmaceutical Companies of Johnson & Johnson
At Janssen, we’re creating a future where disease is a thing of the past. We’re the Pharmaceutical Companies of Johnson & Johnson, working tirelessly to make that future a reality for patients everywhere by fighting sickness with science, improving access with ingenuity, and healing hopelessness with heart. We focus on areas of medicine where we can make the biggest difference: Cardiovascular, Metabolism, & Retina; Immunology; Infectious Diseases & Vaccines; Neuroscience; Oncology; and Pulmonary Hypertension.

Learn more at www.janssen.com. Follow us at www.twitter.com/JanssenGlobal and www.twitter.com/JanssenUS. Janssen Research and Development, LLC and Janssen Biotech, Inc. are part of the Janssen Pharmaceutical Companies of Johnson & Johnson.

AbbVie, J&J Imbruvica gets FDA nod to treat graft-versus-host disease in kids

Aug. 25, 2022 5:38 AM ET

Johnson & Johnson (JNJ), ABBV

By: Ravikash, SA News Editor

The U.S. Food and Drug Administration approved the expanded use of AbbVie (NYSE:ABBV) and Johnson & Johnson's (NYSE:JNJ) Imbruvica for treating patients one year and older with chronic graft versus host disease (cGVHD) after failure of one or more lines of systemic therapy.
https://seekingalpha.com/news/3876504-abbvie-jj-imbruvica-gets-fda-nod-to-treat-graft-versus-host-disease-in-kids
https://seekingalpha.com/symbol/ABBV
https://seekingalpha.com/symbol/JNJ
https://www.imbruvica.com/
https://www.jnj.com/

What is IMBRUVICA® (ibrutinib)? IMBRUVICA® (ibrutinib) is a prescription medicine used to treat adults with: Mantle cell lymphoma (MCL) who have received at least one prior treatment Chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma (SLL) Chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma (SLL) with 17p deletion Waldenström’s macroglobulinemia (WM) Marginal zone lymphoma (MZL) who require a medicine by mouth or injection (systemic therapy) and have received a certain type of prior treatment Chronic graft versus host disease (cGVHD) after failure of 1 or more lines of systemic therapy It is not known if IMBRUVICA® is safe and effective in children.

OPDIVO® (nivolumab) with Chemotherapy

LYNPARZA® (olaparib) in combination with abiraterone

Health Canada Approves OPDIVO® (nivolumab) with Chemotherapy as Neoadjuvant Treatment for Adult Patients with Resectable Non-Small Cell Lung Cancer

Aug. 23, 2022 8:30 AM ET

Bristol-Myers Squibb Company (BMY)

First and-only immunotherapy-based treatment for use before surgery for non-small cell lung cancer in Canada

Significant improvement in event-free survival and pathological complete response

MONTREAL, Aug. 23, 2022 /CNW/ - Today, Bristol Myers Squibb Canada (BMS) announced Health Canada's approval of OPDIVO® (nivolumab) 360 mg (injection for intravenous use) in combination with platinum-doublet chemotherapy every three weeks for three cycles for adult patients with resectable (tumors ≥4 cm or node positive) non-small cell lung cancer (NSCLC) in the neoadjuvant setting.i

"The approval of OPDIVO® plus platinum-doublet chemotherapy in the neoadjuvant setting represents a pivotal transformation in the way we can help patients with resectable non-small cell lung cancer," said Dr Jonathan Spicer, Associate Professor of Surgery, Department of Surgery (Thoracic and Upper GI Surgery), McGill University. "As thoracic surgeons, despite our best efforts to completely remove lung cancers, we see our patients experience recurrence of their disease all too often. My goal is to cure cancer and this new pre-operative treatment combination is now shown to prolong survival and increase the number of patients who have no signs of cancer in their tissues after surgery."

About Lung Cancer & Survival Rates
Lung cancer is the leading cause of cancer death for both males and females in Canada, accounting for over 25 percent of cancer deaths.iii Non–small cell lung cancer (NSCLC) is the most common type of lung cancer making up more than 85 percent of all cases. iii

In NSCLC, 30 to 40 percent are resectable cancers, including most stage I–IIIa and a small proportion of stage IIIb lung cancers.ii
For resectable NSCLC patients who undergo standard of care surgery, 30 to 45 percent will develop recurrence and die of their disease, despite resection.iii

"With the high rates of disease recurrence in patients with resectable NSCLC, this unique pre-operative treatment approach is very welcome news to our patient population," said Shem Singh, Executive Director, Lung Cancer Canada. "This is an important step towards improving the lives of thousands of Canadians living with lung cancer today and in the future.

Clinical Data for Approval
The Health Canada NOC was based on CheckMate-816, which is a Phase 3, randomized, open label trial evaluating OPDIVO® plus platinum-doublet chemotherapy compared to chemotherapy alone as neoadjuvant treatment in adult patients with resectable non-small cell lung cancer (NSCLC), regardless of PD-L1 expression. Published in the New England Journal of Medicine (NEJM), this study demonstrated that in patients with resectable NSCLC, treatment with neoadjuvant OPDIVO® plus chemotherapy resulted in significantly longer event-free survival (EFS) and a higher percentage of patients with a pathological complete response (pCR) than chemotherapy alone.iv

"At BMS, we are driven to understand the complexities of cancer and are leveraging the latest science and technology to develop immunotherapies and combination therapies that push beyond what is currently available. Today's approval is a demonstration to our multifaceted research approach," said Troy André, General Manager, BMS Canada. "We are committed to offering patients the possibility of a better life through treatment options that can make a difference earlier in the course of their disease."

About Bristol Myers Squibb Canada Co.
Bristol Myers Squibb Canada Co. is an indirect wholly-owned subsidiary of Bristol Myers Squibb Company, a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. Bristol Myers Squibb Canada Co. employs close to 300 people across the country. For more information, please visit https://www.bms.com/ca/en.

About Bristol Myers Squibb
Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube, Facebook and Instagram.

SOURCE Bristol Myers Squibb

https://seekingalpha.com/symbol/BMY

https://www.bms.com/

https://www.opdivo.com/

LYNPARZA® (olaparib) in combination with abiraterone

LYNPARZA® (olaparib) in combination with abiraterone granted Priority Review in the US for patients with metastatic castration-resistant prostate cancer

PUBLISHED16 August 2022

First PARP inhibitor to demonstrate clinical benefit in combination with a new hormonal
agent irrespective of homologous recombination repair (HRR) gene mutations

AstraZeneca’s supplemental New Drug Application (sNDA) for LYNPARZA® (olaparib) in combination with abiraterone and prednisone or prednisolone has been accepted and granted Priority Review in the US for the treatment of adult patients with metastatic castration-resistant prostate cancer (mCRPC).

LYNPARZA is being jointly developed and commercialized by AstraZeneca and Merck & Co., Inc., known as MSD outside the US and Canada.

The Food and Drug Administration (FDA) grants Priority Review to applications for medicines that offer significant advantages over available options by demonstrating safety or efficacy improvements, preventing serious conditions, or enhancing patient compliance.1 The Prescription Drug User Fee Act date, the FDA action date for their regulatory decision, is anticipated during the fourth quarter of 2022.

In the US, prostate cancer is the second most common cancer in male patients and is projected to cause approximately 35,000 deaths in 2022.2 Overall survival for patients with mCRPC is approximately three years in clinical trial settings, and even shorter in the real world.3-6 Approximately half of patients with mCRPC may receive only one line of active treatment, with diminishing benefit of subsequent therapies.6-11

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “There remains a critical unmet need among patients diagnosed with metastatic castration-resistant prostate cancer, where the prognosis remains poor and treatment options are limited. Today’s news is another step towards bringing forward a new, much-needed treatment option in this setting. If approved, LYNPARZA with abiraterone will become the first combination of a PARP inhibitor and a new hormonal agent for patients with this disease.”

Dr. Eliav Barr, Senior Vice President, Head of Global Clinical Development and Chief Medical Officer, Merck Research Laboratories, said: “Merck is committed to developing new treatment options for patients with metastatic castration-resistant prostate cancer, a complex disease that urgently needs more therapies. We look forward to working with the FDA towards the goal of bringing a new option to patients with mCRPC with or without HRR gene mutations.”

The sNDA was based on results from the PROpel Phase III trial presented at the 2022 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium and later published in NEJM Evidence.

These results showed LYNPARZA in combination with abiraterone reduced the risk of disease progression or death by 34% versus abiraterone alone (based on a hazard ratio [HR] of 0.66; 95% confidence interval [CI] 0.54-0.81; p<0.0001). Median radiographic progression-free survival (rPFS) was 24.8 months for LYNPARZA plus abiraterone versus 16.6 for abiraterone alone. The safety and tolerability of LYNPARZA in combination with abiraterone was in line with that observed in prior clinical trials and the known profiles of the individual medicines.12

LYNPARZA is approved in the US for patients with HRR gene-mutated mCRPC (BRCA-mutated and other HRR gene mutations) who have progressed following prior treatment with enzalutamide or abiraterone; and in the EU, Japan and China for patients with BRCA-mutated mCRPC who have progressed following prior therapy that included a new hormonal agent. These approvals were based on the data from the PROfound Phase III trial.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

There are no contraindications for LYNPARZA.

WARNINGS AND PRECAUTIONS

Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML): Occurred in approximately 1.5% of patients exposed to LYNPARZA monotherapy, and the majority of events had a fatal outcome. The median duration of therapy in patients who developed MDS/AML was 2 years (range: <6 months to >10 years). All of these patients had previous chemotherapy with platinum agents and/or other DNA-damaging agents, including radiotherapy.

Do not start LYNPARZA until patients have recovered from hematological toxicity caused by previous chemotherapy (≤Grade 1). Monitor complete blood count for cytopenia at baseline and monthly thereafter for clinically significant changes during treatment. For prolonged hematological toxicities, interrupt LYNPARZA and monitor blood count weekly until recovery.

If the levels have not recovered to Grade 1 or less after 4 weeks, refer the patient to a hematologist for further investigations, including bone marrow analysis and blood sample for cytogenetics. Discontinue LYNPARZA if MDS/AML is confirmed.

INDICATIONS

LYNPARZA is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated:

First-Line Maintenance BRCAm Advanced Ovarian Cancer
For the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated (gBRCAm or sBRCAm) advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

First-Line Maintenance HRD-Positive Advanced Ovarian Cancer in Combination with Bevacizumab
In combination with bevacizumab for the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy and whose cancer is associated with homologous recombination deficiency (HRD) positive status defined by either:

a deleterious or suspected deleterious BRCA mutation, and/or
genomic instability

Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

Maintenance Recurrent Ovarian Cancer
For the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, who are in complete or partial response to platinum-based chemotherapy.

Advanced gBRCAm Ovarian Cancer
For the treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) advanced ovarian cancer who have been treated with 3 or more prior lines of chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

Adjuvant Treatment of gBRCAm, HER2-Negative, High-Risk Early Breast Cancer
For the adjuvant treatment of adult patients with deleterious or suspected deleterious gBRCAm, human epidermal growth factor receptor 2 (HER2)-negative high-risk early breast cancer who have been treated with neoadjuvant or adjuvant chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

gBRCAm, HER2-Negative Metastatic Breast Cancer
For the treatment of adult patients with deleterious or suspected deleterious gBRCAm, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer who have been treated with chemotherapy in the neoadjuvant, adjuvant, or metastatic setting. Patients with hormone receptor (HR)-positive breast cancer should have been treated with a prior endocrine therapy or be considered inappropriate for endocrine therapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

First-Line Maintenance gBRCAm Metastatic Pancreatic Cancer
For the maintenance treatment of adult patients with deleterious or suspected deleterious gBRCAm metastatic pancreatic adenocarcinoma whose disease has not progressed on at least 16 weeks of a first-line platinum-based chemotherapy regimen. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

HRR Gene-mutated Metastatic Castration-Resistant Prostate Cancer
For the treatment of adult patients with deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC) who have progressed following prior treatment with enzalutamide or abiraterone. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

Please see complete Prescribing Information, including Medication Guide.

https://www.lynparza.com/

Notes

Metastatic castration-resistant prostate cancer
Metastatic prostate cancer is associated with a significant mortality rate.13 Development of prostate cancer is often driven by male sex hormones called androgens, including testosterone.14

In patients with mCRPC, their prostate cancer grows and spreads to other parts of the body despite the use of androgen-deprivation therapy to block the action of male sex hormones.7 Approximately 10-20% of men with advanced prostate cancer will develop castration-resistant prostate cancer (CRPC) within five years, and at least 84% of these men will have metastases at the time of CRPC diagnosis.7 Of patients with no metastases at CRPC diagnosis, 33% are likely to develop metastases within two years.6

Despite the advances in mCRPC treatment in the past decade with taxane and new hormonal agent (NHA) treatment, there is high unmet need in this population.7,9,10,15

PROpel
PROpel is a randomized, double-blind, multi-center Phase III trial testing the efficacy, safety, and tolerability of LYNPARZA versus placebo when given in addition to abiraterone in men with mCRPC who had not received prior chemotherapy or NHAs in the mCRPC setting.

Men in both treatment groups will also receive either prednisone or prednisolone twice daily. The primary endpoint is rPFS and secondary endpoints include overall survival, time to secondary progression or death, and time to first subsequent therapy.

For more information about the trial please visit ClinicalTrials.gov.

LYNPARZA
LYNPARZA (olaparib) is a first-in-class PARP inhibitor and the first targeted treatment to block DNA damage response (DDR) in cells/tumors harboring a deficiency in HRR, such as those with mutations in BRCA1 and/or BRCA2, or those where deficiency is induced by other agents (such as NHAs).

Inhibition of PARP with LYNPARZA leads to the trapping of PARP bound to DNA single-strand breaks, stalling of replication forks, their collapse and the generation of DNA double-strand breaks and cancer cell death. In the PROpel Phase III trial, LYNPARZA is combined with abiraterone, an NHA which targets the androgen receptor (AR) pathway.

Androgen receptor signaling engages a transcriptional program that is critical for tumor cell growth & survival in prostate cancer.16,17 Preclinical models have identified interactions between PARP signaling and the AR pathway which support the observation of a combined anti-tumor effect of LYNPARZA and NHAs, like abiraterone, in both HRR deficient and HRR proficient prostate cancer.18,19,20

The PARP1 protein has been reported to be required for the transcriptional activity of androgen receptors; therefore inhibiting PARP with LYNPARZA may impair the expression of androgen receptor target genes and enhance the activity of NHAs.16,19,21 Additionally, it is thought that abiraterone may alter/inhibit the transcription of some HRR genes which may induce HRR deficiency and increase sensitivity to PARP inhibition.18,20,22,23

LYNPARZA is currently approved in a number of countries across PARP-dependent tumor types with defects and dependencies in the DDR pathway including maintenance treatment of platinum-sensitive relapsed ovarian cancer and as both monotherapy and in combination with bevacizumab for the 1st-line maintenance treatment of BRCA-mutated (BRCAm) and homologous recombination repair deficient (HRD)-positive advanced ovarian cancer, respectively; for germline BRCAm (gBRCAm) HER2-negative metastatic breast cancer (in the EU and Japan this includes locally advanced breast cancer); for gBRCAm, HER2-negative high-risk early breast cancer; for gBRCAm metastatic pancreatic cancer; and HRR gene-mutated metastatic castration-resistant prostate cancer (BRCAm only in the EU and Japan).

LYNPARZA, which is being jointly developed and commercialized by AstraZeneca and Merck, is the foundation of AstraZeneca's industry-leading portfolio of potential new medicines.

The AstraZeneca and Merck strategic oncology collaboration
In July 2017, AstraZeneca and Merck & Co., Inc., Kenilworth, NJ, US, known as MSD outside the US and Canada, announced a global strategic oncology collaboration to co-develop and co-commercialize LYNPARZA, the world’s first PARP inhibitor, and selumetinib, a mitogen-activated protein kinase (MEK) inhibitor, for multiple cancer types.

Working together, the companies will develop LYNPARZA and selumetinib and other potential new medicines as monotherapies. The companies will also develop LYNPARZA and selumetinib in combination with their respective PD-L1 and PD-1 medicines independently.

The Company's focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyze changes in the practice of medicine and transform the patient experience.

AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.

About AstraZeneca
AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialization of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit www.astrazeneca-us.com and follow the Company on Twitter @AstraZenecaUS.

AstraZeneca/Merck's Lynparza gets FDA priority review to treat prostate cancer subtype

Aug. 16, 2022 4:20 AM ET

AstraZeneca PLC (AZN), JNJ, MRK

By: Ravikash, SA News Editor

The U.S. Food and Drug Administration (FDA) granted priority review to AstraZeneca (NASDAQ:AZN) and Merck's (NYSE:MRK) Lynparza in combination with Johnson & Johnson's (NYSE:JNJ) Zytiga (abiraterone), and prednisone or prednisolone to treat adult patients with metastatic castration-resistant prostate cancer (mCRPC).
https://seekingalpha.com/news/3873395-astrazenecamercks-lynparza-gets-fda-priority-review-to-treat-prostate-cancer-subtype
https://seekingalpha.com/symbol/AZN
https://seekingalpha.com/symbol/MRK

WHAT IS LYNPARZA? LYNPARZA is a prescription medicine used to treat adults who have: advanced ovarian cancer, fallopian tube cancer, or primary peritoneal cancer with a certain type of inherited (germline) or acquired (somatic) abnormal BRCA gene. LYNPARZA is used alone as maintenance treatment after the cancer has responded to your first treatment with platinum-based chemotherapy. Your healthcare provider will perform a test to make sure that LYNPARZA is right for you advanced ovarian cancer, fallopian tube cancer, or primary peritoneal cancer with a certain type of abnormal BRCA gene or a positive laboratory tumor test for genomic instability called HRD. LYNPARZA is used in combination with another anti-cancer medicine, bevacizumab, as maintenance treatment after the cancer has responded to your first treatment with platinum-based chemotherapy. Your healthcare provider will perform a test to make sure that LYNPARZA is right for you ovarian cancer, fallopian tube cancer, or primary peritoneal cancer, as maintenance treatment, when the cancer has come back. LYNPARZA is used after the cancer has responded to treatment with platinum-based chemotherapy advanced ovarian cancer with a certain type of abnormal inherited BRCA gene, and have received treatment with 3 or more prior types of chemotherapy medicines. Your healthcare provider will perform a test to make sure that LYNPARZA is right for you human epidermal growth factor receptor 2 (HER2)-negative early breast cancer with a certain type of inherited (germline) abnormal BRCA gene. LYNPARZA is given after surgery (treatment after surgery is called adjuvant therapy). You should have received chemotherapy medicines before or after surgery to remove the tumor. Your healthcare provider will perform a test to make sure that LYNPARZA is right for you a certain type of abnormal inherited BRCA gene, human epidermal growth factor receptor 2 (HER2)-negative breast cancer that has spread to other parts of the body (metastatic). You should have received chemotherapy medicines, either before or after your cancer has spread. If you have hormone receptor (HR)-positive disease, you should have been treated with hormonal therapy. Your healthcare provider will perform a test to make sure that LYNPARZA is right for you metastatic pancreatic cancer with a certain type of abnormal inherited BRCA gene. LYNPARZA is used as a maintenance treatment after your cancer has not progressed on at least 16 weeks of treatment with platinum-based chemotherapy. Your healthcare provider will perform a test to make sure LYNPARZA is right for you prostate cancer with certain inherited or acquired abnormal genes called homologous recombination repair (HRR genes). LYNPARZA is used when the cancer has spread to other parts of the body (metastatic), and no longer responds to a medical or surgical treatment that lowers testosterone, and has progressed after treatment with enzalutamide or abiraterone. Your healthcare provider will perform a test to make sure LYNPARZA is right for you It is not known if LYNPARZA is safe and effective in children.

BIOTECNOVA™

Trodelvy® (sacituzumab govitecan-hziy)

ENHERTU® (fam-trastuzumab deruxtecan-nxki)

August 15, 2022

Trodelvy® Significantly Improves Overall Survival in Pre-Treated HR+/HER2- Metastatic Breast Cancer Patients in the TROPiCS-02 Study

–Trodelvy is the First TROP-2 Directed ADC to Show a Significant Improvement in Overall Survival in HR+/HER2- Breast Cancer –

– Planned SecondInterim Analysis Demonstrated a Statistically Significant and Clinically Meaningful Benefit for Overall Survival –

FOSTER CITY, Calif.--(BUSINESS WIRE)-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced statistically significant and clinically meaningful results from the second interim analysis of the key secondary endpoint of overall survival (OS) in the Phase 3 TROPiCS-02 study evaluating Trodelvy® (sacituzumab govitecan-hziy) in patients with HR+/HER2- metastatic breast cancer who received prior endocrine therapy, CDK4/6 inhibitors and two to four lines of chemotherapy. Detailed OS results will be presented at an upcoming medical conference. The safety profile for Trodelvy was consistent with prior studies, and no new safety signals emerged in this patient population.

“These survival results from the TROPiCS-02 study are important for the breast cancer community and we are encouraged by the potential this may have in helping patients who otherwise have limited alternatives,” said Merdad Parsey, MD, PhD, Chief Medical Officer, Gilead Sciences. “We look forward to discussing these results with global health authorities, as pre-treated HR+/HER2- metastatic disease patients currently have limited treatment options and poor quality of life.”

Gilead has submitted a supplemental Biologics License Application (sBLA) to the U.S. Food & Drug Administration (FDA). These data will also be shared with health authorities outside the U.S.

In June 2022, based on the positive primary results from the TROPiCS-02 study presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting, the National Comprehensive Cancer Network® (NCCN®) Clinical Practice Guidelines in Oncology (NCCN Guidelines®)i included a category 2A preferred recommendation for sacituzumab govitecan-hziy for the investigational use in patients with HR+/HER2- advanced breast cancer after prior treatment including endocrine therapy, a CDK4/6 inhibitor and at least two lines of chemotherapy. The TROPiCS-02 study enrolled HR+/HER2- metastatic breast cancer patients, which included patients with HER2-low and IHC 0 status.

TROPiCS-02 is an event driven study with planned analyses based on a pre-specified number of events. This interim analysis was executed based on the pre-specified criteria.

Trodelvy has not been approved by any regulatory agency for the treatment of HR+/HER2- metastatic breast cancer. Its safety and efficacy have not been established for this indication. Trodelvy has a Boxed Warning for severe or life-threatening neutropenia and severe diarrhea; please see below for additional Important Safety Information.

About the TROPiCS-02 Study

More information about TROPiCS-02 is available at https://clinicaltrials.gov/ct2/show/NCT03901339.

About Trodelvy

U.S. Indications for Trodelvy

In the United States, Trodelvy is indicated for the treatment of:

Adult patients with unresectable locally advanced or metastatic TNBC who have received two or more prior systemic therapies, at least one of them for metastatic disease.
Adult patients with locally advanced or metastatic UC who have previously received a platinum-containing chemotherapy and either programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
https://www.trodelvy.com/
Please see full Prescribing Information , including BOXED WARNING.

View source version on businesswire.com: https://www.businesswire.com/news/home/20220814005018/en/

Source: Gilead Sciences, Inc.

Gilead says Trodelvy improved overall survival in HR+/HER2- breast cancer

Aug. 15, 2022 8:53 AM ET

Gilead Sciences, Inc. (GILD)

By: Dulan Lokuwithana, SA News Editor7 Comments

Gilead Sciences (NASDAQ:GILD) announced on Monday that its antibody-drug conjugate Trodelvy significantly improved overall survival in certain patients with HR+/HER2- metastatic breast cancer who took part in a Phase 3 trial.
https://seekingalpha.com/news/3872885-gilead-says-trodelvy-improved-overall-survival-in-hrher2-breast-cancer
https://seekingalpha.com/symbol/GILD
https://www.trodelvy.com/
https://www.gilead.com/

ENHERTU® (fam-trastuzumab deruxtecan-nxki)

Enhertu approved in the US as the first HER2-directed therapy for patients with previously treated HER2-mutant metastatic non-small cell lung cancer

PUBLISHED12 August 2022

12 August 2022 07:00 BST

Based on DESTINY-Lung02 results which showed AstraZeneca and Daiichi Sankyo’s Enhertu reported a confirmed objective response rate of 57.7% in patients with HER2-mutant disease

AstraZeneca and Daiichi Sankyo’s Enhertu (trastuzumab deruxtecan) has been approved in the US for the treatment of adult patients with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumours have activating HER2 (ERBB2) mutations, as detected by a Food and Drug Administration (FDA)-approved test, and who have received a prior systemic therapy.

This indication is approved under accelerated approval based on objective response rate (ORR) and duration of response (DoR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Enhertu is a specifically engineered HER2-directed antibody drug conjugate (ADC) being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.

The accelerated approval by the FDA was based on the results from the DESTINY-Lung02 Phase II trial. An interim efficacy analysis in a pre-specified patient cohort showed Enhertu (5.4mg/kg) demonstrated a confirmed ORR of 57.7% (n=52; 95% confidence interval [CI] 43.2-71.3), as assessed by blinded independent central review (BICR), in patients with previously treated unresectable or metastatic non-squamous HER2-mutant (HER2m) NSCLC. Complete responses (CR) were seen in 1.9% of patients and partial responses (PR) in 55.8% of patients with a median DoR of 8.7 months (95% CI 7.1-NE). Results from the DESTINY-Lung02 trial will be presented at an upcoming medical meeting.

Bob T. Li, MD, PhD, MPH, Medical Oncologist and Physician-Scientist, Memorial Sloan Kettering Cancer Center, US, said: “The approval of trastuzumab deruxtecan in non-small cell lung cancer is an important milestone for patients and the oncology community. After two decades of research into the role of targeting HER2 in lung cancer, the approval of the first HER2-directed treatment option validates HER2 as an actionable target in lung cancer and marks an important step forward for treating this patient population with unmet medical needs.”

Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: “HER2-mutant non-small cell lung cancer is an aggressive form of disease which commonly affects young patients who have faced limited treatment options and a poor prognosis to date. Today’s news provides these patients with the opportunity to benefit from a targeted therapy and highlights the importance of testing for predictive markers, including HER2 in lung cancer, at the time of diagnosis to ensure patients receive the most appropriate treatment for their specific disease.”

Ken Keller, Global Head of Oncology Business, and President and CEO, Daiichi Sankyo, Inc, said: “We are excited that the FDA has granted accelerated approval for Enhertu for patients with HER2-mutant metastatic non-small cell lung cancer. Enhertu has now been approved in three different tumour types, underscoring its significant potential across several HER2-targetable tumours. We are continuing to evaluate the efficacy and safety of Enhertu versus standard chemotherapy in our DESTINY clinical trials in lung cancer.”

The safety of Enhertu was evaluated in an analysis of 101 patients with unresectable or metastatic HER2m NSCLC who received at least one dose of Enhertu (5.4mg/kg) in the DESTINY-Lung02 trial. In the analysis, the safety profile of Enhertu was consistent with previous clinical trials with no new safety concerns identified.

Concurrently with this approval, the FDA also approved companion diagnostic tests to detect HER2 mutations in lung tumour tissue and plasma. This is the third tumour type approved by the FDA for Enhertu in three years, following approval in breast and gastric cancers. The approval follows the recently received Priority Review in the US as well as the Breakthrough Therapy Designation granted in 2020 by the FDA for this specific type of lung cancer based on the results of the DESTINY-Lung01 trial.

HER2m NSCLC
Lung cancer is the second most common form of cancer globally, with more than two million patients diagnosed in 2020.1 In the US, lung cancer is the second most commonly diagnosed cancer, with more than 236,000 patients expected to be diagnosed in 2022.2 For patients with metastatic NSCLC, prognosis is particularly poor, as only approximately 8% will live beyond five years after diagnosis.3

HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumours, including lung, breast, gastric and colorectal cancers. Certain HER2 gene alterations (called HER2 mutations) have been identified in patients with non-squamous NSCLC as a distinct molecular target, and occur in approximately 2-4% of patients with this type of lung cancer.4,5 Next-generation sequencing is used to identify HER2 (ERBB2) mutations.6

While HER2 gene mutations can occur in a range of patients, they are more commonly found in patients with NSCLC who are younger, female and have never smoked.7 HER2 gene mutations have been independently associated with cancer cell growth and poor prognosis, with an increased incidence of brain metastases.8 Although the role of anti-HER2 treatment is well established in breast and gastric cancers, there were no approved HER2-directed therapies in NSCLC prior to the accelerated approval of Enhertu in unresectable or metastatic NSCLC.8,9

DESTINY-Lung02
DESTINY-Lung02 is a global Phase II trial evaluating the safety and efficacy of two doses (5.4mg/kg or 6.4mg/kg) of Enhertu in patients with HER2m metastatic NSCLC with disease recurrence or progression during or after at least one regimen of prior anticancer therapy that must have contained a platinum-based chemotherapy.

The primary endpoint of the trial is ORR as assessed by BICR. Secondary endpoints include disease control rate (DCR), DoR, progression-free survival (PFS), investigator-assessed ORR, overall survival (OS) and safety.

DESTINY-Lung02 enrolled 152 patients at multiple sites, including Asia, Europe and North America. For more information about the trial, visit ClinicalTrials.gov.

DESTINY-Lung01
DESTINY-Lung01 is a global Phase II, open-label, two-cohort trial evaluating the safety and efficacy of Enhertu in patients with HER2m (6.4mg/kg) or HER2-overexpressing (defined as IHC 3+ or IHC 2+) [6.4mg/kg and 5.4mg/kg] unresectable and/or metastatic non-squamous NSCLC who had progressed after one or more systemic therapies. The primary endpoint is confirmed ORR by independent central review (ICR). Key secondary endpoints include DoR, DCR, PFS, OS and safety. DESTINY-Lung01 enrolled 181 patients at multiple sites, including Asia, Europe and North America.

Data from the DESTINY-Lung01 Phase II trial was published in The New England Journal of Medicine.10 Primary results from previously-treated patients with HER2-mutations (cohort 2) of DESTINY-Lung01 demonstrated an ORR of 54.9% (95% CI 44.2-65.4) in patients treated with Enhertu (6.4mg/kg) as assessed by ICR. One (1.1%) CR and 49 (53.8%) PRs were observed. A confirmed DCR of 92.3% was seen with a reduction in tumour size observed in most patients. After a median follow-up of 13.1 months, the median DoR for Enhertu was 9.3 months. The median PFS was 8.2 months and the median OS was 17.8 months.

The safety profile of the most common adverse events with Enhertu in DESTINY-Lung01 was consistent with previous clinical trials with no new safety concerns identified. For more information about the trial, visit ClinicalTrials.gov.

Enhertu
Enhertu is a HER2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, Enhertu is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced programme in AstraZeneca’s ADC scientific platform.

Enhertu consists of a HER2 monoclonal antibody attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a stable tetrapeptide-based cleavable linker.

Enhertu (5.4mg/kg) is approved in the US for the treatment of adult patients with unresectable or metastatic NSCLC whose tumours have activating HER2 (ERBB2) mutations, as detected by an FDA-approved test, and who have received a prior systemic therapy based on the results from the DESTINY-Lung02 trial.

https://www.enhertu.com/

Daiichi Sankyo collaboration
Daiichi Sankyo Company, Limited (TSE: 4568) [referred to as Daiichi Sankyo] and AstraZeneca entered into a global collaboration to jointly develop and commercialise Enhertu (a HER2-directed ADC) in March 2019, and datopotamab deruxtecan (a TROP2-directed ADC) in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights. Daiichi Sankyo is responsible for the manufacturing and supply of Enhertu and datopotamab deruxtecan.

AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.

AstraZeneca, Daiichi Sankyo's Enhertu gets FDA approval for lung cancer subtype

Aug. 12, 2022 7:17 AM ET

AstraZeneca PLC (AZN), DSKYF, DSNKY

By: Ravikash, SA News Editor

The U.S. Food and Drug Administration (FDA) approved AstraZeneca (NASDAQ:AZN) and Daiichi Sankyo's (OTCPK:DSKYF) (OTCPK:DSNKY) Enhertu to treat adult patients with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have activating HER2 (ERBB2) mutations.
https://seekingalpha.com/news/3872247-astrazeneca-daiichi-sankyos-enhertu-gets-fda-approval-for-lung-cancer-subtype
https://seekingalpha.com/symbol/DSKYF
https://seekingalpha.com/symbol/DSNKY
https://seekingalpha.com/symbol/AZN
https://www.enhertu.com/
https://www.astrazeneca.com/

Enhertu significantly delayed disease progression in DESTINY-Breast02 Phase III trial vs. physician’s choice of treatment in patients with HER2-positive metastatic breast cancer

PUBLISHED15 August 2022 15 August 2022 07:00 BST

Results consistent with previous trials, reinforcing benefit of AstraZeneca and Daiichi Sankyo’s Enhertu in previously treated patients

https://www.astrazeneca.com/media-centre/press-releases/2022/enhertu-improved-pfs-in-mbc-in-destiny-breast02.html

https://www.enhertu.com/

https://seekingalpha.com/news/3872711-astrazeneca-daiichi-sankyos-enhertu-delays-breast-cancer-progression-meets-study-goals

https://seekingalpha.com/symbol/AZN

What is ENHERTU? ENHERTU (en-HER-too) is a prescription medicine used to treat adults who have: human epidermal growth factor receptor 2 (HER2)-positive breast cancer that cannot be removed by surgery or that has spread to other parts of the body (metastatic), and who have received a prior anti-HER2 breast cancer treatment: for metastatic disease, or have breast cancer that has come back during or within 6 months of completing treatment for their early-stage breast cancer. HER2-low breast cancer that cannot be removed by surgery or that has spread to other parts of your body (metastatic), and who have received a prior chemotherapy: for metastatic disease, or your disease has returned during or within 6 months of completing adjuvant chemotherapy (after surgery). Your healthcare provider will perform a test to make sure ENHERTU is right for you. stomach cancer called gastric or gastroesophageal junction (GEJ) adenocarcinoma that is HER2-positive and has spread to areas near your stomach (locally advanced) or that has spread to other parts of your body (metastatic), and who have received a prior trastuzumab-based regimen It is not known if ENHERTU is safe and effective in children.

Lynparza (olaparib)

ENHERTU® (fam-trastuzumab deruxtecan-nxki)

CALQUENCE® (acalabrutinib)

Lynparza receives Health Canada approval as adjuvant treatment for patients with germline BRCA-mutated HER2-negative high-risk early breast cancer

Aug. 11, 2022 8:00 AM ET

AstraZeneca PLC (AZN)

First and only approved medicine targeting germline BRCA mutations in high-risk early breast cancer

MISSISSAUGA, ON, Aug. 11, 2022 /CNW/ - Health Canada has granted a Notice of Compliance with Conditions (NOC/c) for Lynparza® (olaparib) for the adjuvant treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm), human epidermal growth factor receptor 2 (HER2)-negative high-risk early breast cancer who have been treated with neoadjuvant or adjuvant chemotherapy.1 Patients must have confirmation of a germline BRCA mutation before Lynparza treatment is initiated.1

This approval was granted under Health Canada's accelerated review pathway and based on results from the OlympiA Phase III trial,1 presented during the 2021 American Society of Clinical Oncology Annual Meeting and published in The New England Journal of Medicine. The OlympiA trial demonstrated a reduction in the risk of invasive breast cancer recurrences, second cancers or death by 42 per cent versus placebo (based on a hazard ratio [HR] of 0.58; 95% confidence interval [CI] 0.41-0.82; p<0.0001).1

"Although most HER2-negative early breast cancers now have excellent outcomes, the risk of disease recurrence for persons with high-risk breast cancers and BRCA mutations remains unacceptably high, with a significant potential to advance to advanced disease, where a cure is no longer an option," said Dr. Karen Gelmon, Professor of Medicine, University of British Columbia and Medical Oncologist, BC Cancer. "Today's approval of olaparib is an important step forward, offering these patients a much-needed option that can improve survival for persons with high-risk early breast cancer. It also stresses the importance of BRCA testing as soon as possible after diagnosis to identify eligible patients."

In Canada, it is estimated that 94 per cent of all breast cancers are detected at an early stage.2 Despite advances in the treatment of early breast cancer, up to 30 per cent of patients with high-risk clinical and/or pathologic features recur within the first few years.3 The risk is particularly high for patients with germline BRCA mutations, who are more likely to be diagnosed at a younger age than those without these mutations.2

"This approval is fantastic news for the many women with high-risk early breast cancer who live with the ongoing fear of recurrence and what that means for their future," said Cathy Ammendolea, Chair of the Board, Canadian Breast Cancer Network. "New treatment options can provide hope for patients and their families, and we look forward to Canadian women having access to this treatment."

"Hereditary breast cancer is often diagnosed at a younger age and Rethink has supported and advocated for young people with breast cancer for more than 20 years. Facing their mortality at a young age, they want what all cancer patients want – care that will lead to the best possible outcome, including reducing their future cancer risk," said MJ DeCoteau, Founder and Executive Director of Rethink Breast Cancer. "They want to survive, and eventually thrive, and now patients with a BRCA-mutated breast cancer will have a treatment that is shown to help them do just that."

About the OlympiA Phase III Trial

OlympiA is a Phase III, double-blind, placebo-controlled, multicentre trial testing the efficacy and safety of Lynparza as adjuvant treatment in patients with gBRCAm HER2-negative high-risk early breast cancer, who have completed definitive local treatment and neoadjuvant or adjuvant chemotherapy.1 The primary endpoint was invasive disease-free survival (iDFS), and key secondary outcome measures include distant disease-free survival (DDFS) and overall survival (OS).1

In the key secondary endpoint, results showed an improvement of distant disease-free survival (DDFS) in the intention to treat (ITT) population, where Lynparza reduced the risk of distant disease recurrence or death by 43 per cent (based on a HR of 0.57 (99.5% CI:0.39-0.83; P < 0.001).1 Interim overall survival (8% maturity, DCO 27 March 2020) did not meet statistical significance.1

The safety and tolerability profile of Lynparza in this trial was in line with that observed in prior clinical trials.1

About Lynparza (olaparib)

Lynparza was the first oral (PARP) inhibitor approved in Canada. Lynparza exploits tumour DNA damage response (DDR) in cells/tumours harbouring a deficiency in homologous recombination repair (HRR), such as mutations in BRCA1 and/or BRCA2, to selectively kill cancer cells.1 Lynparza is the only PARP inhibitor currently approved in multiple tumour types in Canada including breast, ovarian, pancreatic and prostate cancers.

Lynparza has been issued conditional marketing authorization for the adjuvant treatment of adult patients with deleterious or suspected deleterious gBRCAm, HER2-negative high-risk early breast cancer who have been treated with neoadjuvant or adjuvant chemotherapy pending the results of studies to verify its clinical benefit. Patients should be advised of this conditional marketing authorization.

About AstraZeneca (AZN)

AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialization of prescription medicines in Oncology, Rare Diseases, and Biopharmaceuticals, including Cardiovascular, Renal & Metabolism (CVRM), and Respiratory & Immunology. The company employs more than 1,200 people across Canada, including 700 employees at our head office and clinical research hub in Mississauga, Ontario. For more information, please visit the company's website at www.astrazeneca.ca.

SOURCE AstraZeneca Canada Inc.

https://seekingalpha.com/symbol/AZN

https://www.astrazeneca.com/

https://www.lynparza.com/

WHAT IS LYNPARZA? LYNPARZA is a prescription medicine used to treat adults who have: advanced ovarian cancer, fallopian tube cancer, or primary peritoneal cancer with a certain type of inherited (germline) or acquired (somatic) abnormal BRCA gene. LYNPARZA is used alone as maintenance treatment after the cancer has responded to your first treatment with platinum-based chemotherapy. Your healthcare provider will perform a test to make sure that LYNPARZA is right for you advanced ovarian cancer, fallopian tube cancer, or primary peritoneal cancer with a certain type of abnormal BRCA gene or a positive laboratory tumor test for genomic instability called HRD. LYNPARZA is used in combination with another anti-cancer medicine, bevacizumab, as maintenance treatment after the cancer has responded to your first treatment with platinum-based chemotherapy. Your healthcare provider will perform a test to make sure that LYNPARZA is right for you ovarian cancer, fallopian tube cancer, or primary peritoneal cancer, as maintenance treatment, when the cancer has come back. LYNPARZA is used after the cancer has responded to treatment with platinum-based chemotherapy advanced ovarian cancer with a certain type of abnormal inherited BRCA gene, and have received treatment with 3 or more prior types of chemotherapy medicines. Your healthcare provider will perform a test to make sure that LYNPARZA is right for you human epidermal growth factor receptor 2 (HER2)-negative early breast cancer with a certain type of inherited (germline) abnormal BRCA gene. LYNPARZA is given after surgery (treatment after surgery is called adjuvant therapy). You should have received chemotherapy medicines before or after surgery to remove the tumor. Your healthcare provider will perform a test to make sure that LYNPARZA is right for you a certain type of abnormal inherited BRCA gene, human epidermal growth factor receptor 2 (HER2)-negative breast cancer that has spread to other parts of the body (metastatic). You should have received chemotherapy medicines, either before or after your cancer has spread. If you have hormone receptor (HR)-positive disease, you should have been treated with hormonal therapy. Your healthcare provider will perform a test to make sure that LYNPARZA is right for you metastatic pancreatic cancer with a certain type of abnormal inherited BRCA gene. LYNPARZA is used as a maintenance treatment after your cancer has not progressed on at least 16 weeks of treatment with platinum-based chemotherapy. Your healthcare provider will perform a test to make sure LYNPARZA is right for you prostate cancer with certain inherited or acquired abnormal genes called homologous recombination repair (HRR genes). LYNPARZA is used when the cancer has spread to other parts of the body (metastatic), and no longer responds to a medical or surgical treatment that lowers testosterone, and has progressed after treatment with enzalutamide or abiraterone. Your healthcare provider will perform a test to make sure LYNPARZA is right for you It is not known if LYNPARZA is safe and effective in children.

CALQUENCE® (acalabrutinib)

ENHERTU® (trastuzumab deruxtecan; fam-trastuzumab deruxtecan-nxki in the U.S. only)

CALQUENCE® (acalabrutinib)

Calquence tablet formulation approved in the US across current indications

PUBLISHED5 August 2022

5 August 2022 12:00 BST

New formulation can be co-administered with gastric acid-reducing agents

Tablet offers equivalent efficacy, safety and consistent dosing compared to current capsule

AstraZeneca’s new tablet formulation of Calquence (acalabrutinib) has been approved in the US for all current indications, including adult patients with chronic lymphocytic leukaemia (CLL), small lymphocytic lymphoma (SLL) and for patients with relapsed or refractory mantle cell lymphoma (MCL), which is approved under accelerated approval based on overall response rate.

The approval by the US Food and Drug Administration (FDA) was based on results from the ELEVATE-PLUS trials presented during the 63rd American Society of Hematology (ASH) Annual Meeting & Exposition in December 2021.1

In the trials, results showed the Calquence capsule and tablet formulations are bioequivalent, indicating the same efficacy and safety profile can be expected with the same dosing strength and schedule.1 The tablet can be taken with gastric acid-reducing agents, including proton pump inhibitors (PPIs), antacids and H2-receptor antagonists (H2RAs).1,2 The majority of observed adverse events (AEs) in these studies were mild with no new safety concerns identified.1

John C. Byrd, MD, Chair of the Department of Internal Medicine at the University of Cincinnati, said: “Patients with blood cancers like chronic lymphocytic leukaemia and mantle cell lymphoma are often older and may face multiple medical conditions that may need intervention, including acid reflux or peptic ulcer disease. The US approval of acalabrutinib in a tablet form enables co-administration of the acalabrutinib tablet alongside a proton pump inhibitor. This provides another option for some patients with chronic lymphocytic leukaemia and relapsed or refractory mantle cell lymphoma, enabling more patients to potentially benefit from this treatment.”

Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: “Today’s approval of the new Calquence tablet formulation will offer physicians and patients increased flexibility when devising treatment plans for chronic lymphocytic leukaemia and mantle cell lymphoma. This new option is a result of our focus on understanding the wants and needs of this community and providing patient-focused solutions for their treatment.”

Calquence is also approved as a capsule formulation for the same indications as the tablet in the US and in many other countries worldwide.3 Indications may vary by market.

ELEVATE-PLUS
ELEVATE-PLUS is comprised of three Phase I, open-label, single-dose, cross-over studies conducted in 116 healthy subjects. The trials established bioequivalence between acalabrutinib tablets (100mg) and acalabrutinib (100mg) capsules, evaluated the PPI effect of acalabrutinib tablets administered in the presence versus absence of PPI rabeprazole and investigated the effect of food by comparing acalabrutinib tablets administered with a high-fat diet versus fasted.1

Calquence
Calquence (acalabrutinib) is a next-generation, selective inhibitor of Bruton’s tyrosine kinase (BTK). Calquence binds covalently to BTK, thereby inhibiting its activity.3,10 In B cells, BTK signalling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis and adhesion.3

Calquence is available for prescribing in capsule and tablet formulations in the US. Calquence tablets and capsules are approved in the US for the treatment of CLL and SLL, and for the treatment of adult patients with MCL who have received at least one prior therapy. Capsules have restrictions in relation to use with gastric acid reducing agents. The tablets are not licensed in the European Union.

Calquence capsules are approved for CLL in the EU and many other countries worldwide and approved in Japan for relapsed or refractory CLL and SLL. A Phase I trial is currently underway in Japan for the treatment of front-line CLL.

In the US and several other countries, Calquence capsules are also approved for the treatment of adult patients with MCL who have received at least one prior therapy. The US MCL indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Calquence is not currently approved for the treatment of MCL in Europe or Japan.

As part of an extensive clinical development programme, AstraZeneca and Acerta Pharma are currently evaluating Calquence in more than 20 company-sponsored clinical trials. Calquence is being evaluated for the treatment of multiple B-cell blood cancers, including CLL, MCL, diffuse large B-cell lymphoma, Waldenström’s macroglobulinaemia, follicular lymphoma and marginal zone lymphoma.

https://www.calquence.com/

AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on Twitter @AstraZeneca

AstraZeneca cancer drug Calquence's tablet form gets FDA approval

Aug. 08, 2022 5:13 AM ET

AstraZeneca PLC (AZN)

By: Ravikash, SA News Editor1 Comment

AstraZeneca (NASDAQ:AZN) said on Aug. 5 that the U.S. Food and Drug Administration (FDA) approved a new tablet formulation of Calquence (acalabrutinib) for all current uses.
https://seekingalpha.com/news/3868602-astrazeneca-cancer-drug-calquences-tablet-form-gets-fda-approval
https://seekingalpha.com/symbol/AZN
https://www.calquence.com/
https://www.astrazeneca-us.com/
https://www.astrazeneca-us.com/media/press-releases/2022/calquence-acalabrutinib-tablet-formulation-approved-in-the-us-across-current-indications-08052022.html

What is CALQUENCE? CALQUENCE is a prescription medicine used to treat adults with mantle cell lymphoma (MCL) who have received at least one prior treatment for their cancer, or adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). It is not known if CALQUENCE is safe and effective in children.

ENHERTU® (trastuzumab deruxtecan; fam-trastuzumab deruxtecan-nxki in the U.S. only)

ENHERTU® Granted Priority Review in the U.S. for Patients with HER2 Low Metastatic Breast Cancer • Based on DESTINY-Breast04 results which showed Daiichi Sankyo and AstraZeneca’s ENHERTU is the first HER2 directed therapy to demonstrate a survival benefit in this population • Application being evaluated under FDA Real-Time Oncology Review and Project Orbis Tokyo and Basking Ridge, NJ – (July 25, 2022) – Daiichi Sankyo (TSE: 4568) and AstraZeneca (LSE/STO/Nasdaq: AZN) have received notification of acceptance by the U.S. Food and Drug Administration (FDA) of the supplemental Biologics License Application (sBLA) of ENHERTU® (famtrastuzumab deruxtecan-nxki) for the treatment of adult patients with unresectable or metastatic HER2 low (immunohistochemistry (IHC) 1+ or IHC 2+/in-situ hybridization (ISH)-negative) breast cancer who have received a prior therapy in the metastatic setting. The application has been granted Priority Review. ENHERTU is a specifically engineered HER2 directed antibody drug conjugate (ADC) being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca. The FDA grants Priority Review to applications for medicines that, if approved, would offer significant improvements over available options by demonstrating safety or efficacy improvements, preventing serious conditions or enhancing patient compliance. The Prescription Drug User Fee Act date (PDUFA), the FDA action date for their regulatory decision, is during the fourth quarter of the 2022 calendar year. The Priority Review follows receipt of Breakthrough Therapy Designation, granted by the FDA in April 2022 for ENHERTU in metastatic HER2 low breast cancer. The sBLA is being reviewed under the Real-Time Oncology Review (RTOR) program and Project Orbis, two initiatives of the FDA which are designed to bring safe and effective cancer treatments to patients as early as possible. RTOR allows the FDA to review components of an application before submission of the complete application. Project Orbis provides a framework for concurrent submission and review of oncology medicines among participating international partners. “The results seen in the DESTINY-Breast04 trial represent a significant advance and reinforce the potential for ENHERTU to become a new standard of care for patients with previously treated HER2 low metastatic breast cancer,” said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. “The prioritization of this 2 application by the FDA and inclusion in both the Real-Time Oncology Review and Project Orbis initiatives support the importance of these data, and we look forward to working with the FDA to potentially bring ENHERTU to patients with HER2 low metastatic breast cancer as quickly as possible.” “The data from DESTINY-Breast04 represent the first time a HER2 targeted therapy has shown a survival benefit in patients with HER2 low metastatic breast cancer,” said Susan Galbraith, MBBChir, PhD, Executive Vice President, Oncology R&D, AstraZeneca. “For more than two decades, only patients with HER2 positive breast cancer have been able to benefit from HER2 targeted therapies. If approved, ENHERTU will redefine how we classify and treat metastatic breast cancer, enabling patients whose tumors have lower levels of HER2 expression the opportunity to benefit from a HER2 directed therapy.” The sBLA is based on data from the DESTINY-Breast04 phase 3 trial recently presented at the presidential plenary session of the American Society of Clinical Oncology (#ASCO22) Annual Meeting and simultaneously published in The New England Journal of Medicine. In DESTINY-Breast04, ENHERTU demonstrated superior and clinically meaningful efficacy in progression-free survival (PFS) and overall survival (OS) in previously treated patients with HER2 low unresectable and/or metastatic breast cancer with hormone receptor (HR) positive or HR negative disease versus standard of care physician’s choice of chemotherapy. The safety profile of ENHERTU was consistent with previous clinical trials with no new safety concerns identified. Interstitial lung disease (ILD) or pneumonitis rates were consistent with those observed in other late-line HER2 positive breast cancer trials of ENHERTU, as determined by an independent adjudication committee. About DESTINY-Breast04 DESTINY-Breast04 is a global, randomized, open-label, pivotal phase 3 trial evaluating the efficacy and safety of ENHERTU (5.4 mg/kg) versus physician’s choice of chemotherapy (capecitabine, eribulin, gemcitabine, paclitaxel or nab-paclitaxel) in patients with HR positive or HR negative, HER2 low unresectable and/or metastatic breast cancer previously treated with one or two prior lines of chemotherapy. Patients were randomized 2:1 to receive either ENHERTU or chemotherapy. The primary endpoint of DESTINY-Breast04 is PFS in patients with HR positive disease based on blinded independent central review (BICR). Key secondary endpoints include PFS based on BICR in all randomized patients (HR positive and HR negative disease), OS in patients with HR positive disease and OS in all randomized patients (HR positive and HR negative disease). Other secondary endpoints include PFS based on investigator assessment, objective response rate based on BICR and on investigator assessment, duration of response based on BICR and safety. DESTINY-Breast04 enrolled 557 patients at multiple sites in Asia, Europe and North America. For more information about the trial, visit ClinicalTrials.gov.

About ENHERTU ENHERTU® (trastuzumab deruxtecan; fam-trastuzumab deruxtecan-nxki in the U.S. only) is a HER2 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, ENHERTU is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced program in AstraZeneca’s ADC scientific platform. ENHERTU consists of a HER2 monoclonal antibody attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a stable tetrapeptide-based cleavable linker. ENHERTU (5.4 mg/kg) is approved in more than 30 countries for the treatment of adult patients with unresectable or metastatic HER2 positive breast cancer who have received a prior anti-HER2-based regimen either in the metastatic setting, or in the neoadjuvant or adjuvant setting and have developed disease recurrence during or within six months of completing therapy, based on results from the DESTINY-Breast03 4 trial. ENHERTU also is approved in several countries for the treatment of adult patients with unresectable or metastatic HER2 positive breast cancer who have received two or more prior anti-HER2-based regimens based on the results from the DESTINY-Breast01 trial. ENHERTU (6.4 mg/kg) is approved in several countries for the treatment of adult patients with locally advanced or metastatic HER2 positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 trial. ENHERTU is approved in the U.S. with Boxed WARNINGS for Interstitial Lung Disease and Embryo-Fetal Toxicity. For more information, please see the accompanying full Prescribing Information, including Boxed WARNINGS, and Medication Guide. About the ENHERTU Clinical Development Program A comprehensive global development program is underway evaluating the efficacy and safety of ENHERTU monotherapy across multiple HER2 targetable cancers including breast, gastric, lung and colorectal cancers. Trials in combination with other anticancer treatments, such as immunotherapy, also are underway. Regulatory applications for ENHERTU are currently under review in China, Japan and several other countries for the treatment of adult patients with HER2 positive unresectable or metastatic breast cancer who have received a prior anti-HER2-based regimen based on the results from the DESTINY-Breast03 trial. ENHERTU is under review in Europe and Japan for the treatment of adult patients with unresectable or metastatic HER2 low (IHC 1+ or IHC 2+/ISH-negative) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy, based on the results from the DESTINY-Breast04 trial. Patients with HR positive breast cancer must additionally have received or be ineligible for endocrine therapy. ENHERTU also is currently under review in the U.S. for the treatment of adult patients with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have a HER2 (ERBB2) mutation and who have received a prior systemic therapy based on the results from the DESTINY-Lung01 trial, and in Europe for the treatment of adult patients with locally advanced or metastatic HER2 positive gastric or GEJ adenocarcinoma who have received a prior anti-HER2-based regimen based on the DESTINY-Gastric01 and DESTINY-Gastric02 trials. 5 About the Daiichi Sankyo and AstraZeneca Collaboration Daiichi Sankyo Company, Limited (referred to as Daiichi Sankyo) and AstraZeneca entered into a global collaboration to jointly develop and commercialize ENHERTU in March 2019 and datopotamab deruxtecan (Dato-DXd) in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is responsible for the manufacturing and supply of ENHERTU and datopotamab deruxtecan.

Indications ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with: • Unresectable or metastatic HER2-positive breast cancer who have received a prior anti-HER2-based regimen either: – In the metastatic setting, or – In the neoadjuvant or adjuvant setting and have developed disease recurrence during or within six months of completing therapy • Locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen

https://www.enhertu.com/en

Please see accompanying full Prescribing Information, including Boxed WARNINGS, and Medication Guide. About Daiichi Sankyo Daiichi Sankyo is dedicated to creating new modalities and innovative medicines by leveraging our world-class science and technology for our purpose “to contribute to the enrichment of quality of life around the world.” In addition to our current portfolio of medicines for cancer and cardiovascular disease, Daiichi Sankyo is primarily focused on developing novel therapies for people with cancer as well as other diseases with high unmet medical needs. With more than 100 years of scientific expertise and a presence in more than 20 countries, Daiichi Sankyo and its 16,000 employees around the world draw upon a rich legacy of innovation to realize our 2030 Vision to become an “Innovative Global Healthcare Company Contributing to the Sustainable Development of Society.” For more information, please visit: www.daiichisankyo.com.

AstraZeneca, Daiichi Sankyo win FDA label expansion for Enhertu in HER2-low breast cancer

Aug. 05, 2022 12:16 PM ET

AstraZeneca PLC (AZN)DSKYF, DSNKY

By: Dulan Lokuwithana, SA News Editor1 Comment

The U.S. Food and Drug Administration (FDA) on Friday approved the cancer medication Enhertu, developed by AstraZeneca (NASDAQ:AZN) and its Japanese partner Daiichi Sankyo (OTCPK:DSKYF) (OTCPK:DSNKY), for adult patients with HER2-low breast cancer.
https://seekingalpha.com/news/3868282-astrazeneca-daiichi-sankyo-win-fda-label-expansion-for-enhertu
https://seekingalpha.com/symbol/AZN
https://www.astrazeneca.com/
https://seekingalpha.com/symbol/DSKYF
https://seekingalpha.com/symbol/DSNKY
https://www.enhertu.com/en

What is ENHERTU? ENHERTU is a prescription medicine used in adults to treat human epidermal growth factor receptor 2 (HER2)-positive: Breast cancer that cannot be removed by surgery or that has spread to other parts of the body (metastatic), and who have received a prior anti-HER2 breast cancer treatment: for metastatic disease, or have breast cancer that has come back during or within 6 months of completing treatment for their early-stage breast cancer. Stomach cancer called gastric or gastroesophageal junction (GEJ) adenocarcinoma that has spread to areas near your stomach (locally advanced) or that has spread to other parts of your body (metastatic), and who have received a prior trastuzumab-based regimen. It is not known if ENHERTU is safe and effective in children.

LYNPARZA® (olaparib) tablets

ENHERTU® (trastuzumab deruxtecan; fam-trastuzumab deruxtecan-nxki in the U.S. only)

Lynparza approved in the EU as adjuvant treatment for patients with germline BRCA-mutated HER2-negative high-risk early breast cancer

PUBLISHED4 August 2022

4 August 2022 07:00 BST

First and only approved medicine targeting
BRCA mutations in early breast cancer

AstraZeneca and MSD’s Lynparza (olaparib) has been approved in the European Union (EU) as monotherapy or in combination with endocrine therapy for the adjuvant treatment of adult patients with germline BRCA1/2 mutations (gBRCAm), who have human epidermal growth factor receptor 2 (HER2)-negative high-risk early breast cancer previously treated with neoadjuvant or adjuvant chemotherapy.

This approval by the European Commission was based on results from the OlympiA Phase III trial published in The New England Journal of Medicine in June 2021 and follows the recommendation for approval in the EU by the Committee for Medicinal Products for Human Use of Lynparza in this setting.1 In the trial, Lynparza demonstrated a statistically significant and clinically meaningful improvement in invasive disease-free survival (iDFS), reducing the risk of invasive breast cancer recurrences, new cancers, or death by 42% versus placebo (based on a hazard ratio [HR] of 0.58; 99.5% confidence interval [CI] 0.41-0.82; p<0.0001).

Lynparza also demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS), reducing the risk of death by 32% versus placebo (based on a HR of 0.68; 98.5% CI 0.47-0.97; p=0.009). The safety and tolerability profile of Lynparza in this trial was in line with that observed in prior clinical trials.

Breast cancer is the most diagnosed cancer worldwide with an estimated 2.3 million patients diagnosed in 2020.2 Approximately 90% of all breast cancer patients worldwide are diagnosed with early breast cancer and BRCA mutations are found in approximately 10% of HER2-negative patients in Europe.3-5

Professor Andrew Tutt, Global Chair of the OlympiA Phase III trial and Professor of Oncology at The Institute of Cancer Research, London and King’s College London, said: “Today’s approval marks a new era of care in Europe for patients with an inherited form of breast cancer. For patients with high-risk early-stage breast cancer, including those with germline BRCA mutations, recurrence rates remain unacceptably high, with more than one in four of these patients seeing their cancer return following surgery and systemic treatment. Olaparib is the first PARP inhibitor to demonstrate improved overall survival for high-risk early-stage breast cancer patients with germline BRCA mutations and I am hopeful it will become a new standard of care.”

Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said:

“With this approval, Lynparza is now the first and only PARP inhibitor available for patients with germline BRCA-mutated HER2-negative early breast cancer in Europe. We can now bring the benefits of Lynparza to this earlier setting to help reduce the risk of life-threatening recurrence.”

Dr Eliav Barr, Senior Vice President, Head of Global Clinical Development and Chief Medical Officer, MSD Research Laboratories, said: “Today’s approval offers patients with germline BRCA-mutated HER2-negative early-stage breast cancer a new, much-needed treatment option. Lynparza as adjuvant treatment can significantly reduce the risk of disease recurrence and death, reinforcing the importance of conducting germline BRCA testing as soon as possible after diagnosis.”

In March 2022, Lynparza was approved in the US for the treatment of gBRCAm, HER2-negative high-risk early breast cancer. Lynparza is also approved in the US, EU, Japan, and many other countries for the treatment of patients with gBRCAm, HER2-negative, metastatic breast cancer previously treated with chemotherapy based on results from the OlympiAD Phase III trial. In the EU, this indication also includes patients with locally advanced breast cancer.

OlympiA
OlympiA is a Phase III, double-blind, parallel group, placebo-controlled, multicentre trial testing the efficacy and safety of Lynparza tablets versus placebo as adjuvant treatment in patients with gBRCAm high-risk HER2-negative early breast cancer, who have completed definitive local treatment and neoadjuvant or adjuvant chemotherapy.12

The primary endpoint of the trial was iDFS defined as time from randomisation to date of first locoregional or distant recurrence or new cancer or death from any cause.1

BRCA
BRCA1 and BRCA2 are human genes that produce proteins responsible for repairing damaged DNA and play an important role maintaining the genetic stability of cells.9 When either of these genes is mutated or altered such that its protein product either is not made or does not function correctly, DNA damage may not be repaired properly, and cells become unstable. As a result, cells are more likely to develop additional alterations that can lead to cancer. Cancers with BRCA mutations are more likely to be sensitive to PARP inhibitors including Lynparza.13-16

Lynparza
Lynparza (olaparib) is a first-in-class PARP inhibitor and the first targeted treatment to block DNA damage response (DDR) in cells/tumours harbouring a deficiency in homologous recombination repair (HRR), such as those with mutations in BRCA1 and/or BRCA2, or those where deficiency is induced by other agents (such as new hormonal agents – NHAs).

https://www.lynparza.com/

AstraZeneca/Merck's Lynparza gets approval in EU for expanded use in breast cancer subtype

Aug. 04, 2022 5:41 AM ET

AstraZeneca PLC (AZN), MRK

By: Ravikash, SA News Editor

AstraZeneca (NASDAQ:AZN) and Merck's (NYSE:MRK) medicine Lynparza was approved for expanded use in treating certain patients with breast cancer in the EU.
https://seekingalpha.com/news/3866864-astrazenecamercks-lynparza-gets-approval-in-eu-for-expanded-use-in-breast-cancer-subtype
https://seekingalpha.com/symbol/MRK
https://seekingalpha.com/symbol/AZN
https://www.lynparza.com/

WHAT IS LYNPARZA? LYNPARZA is a prescription medicine used to treat adults who have: advanced ovarian cancer, fallopian tube cancer, or primary peritoneal cancer with a certain type of inherited (germline) or acquired (somatic) abnormal BRCA gene. LYNPARZA is used alone as maintenance treatment after the cancer has responded to your first treatment with platinum-based chemotherapy. Your healthcare provider will perform a test to make sure that LYNPARZA is right for you advanced ovarian cancer, fallopian tube cancer, or primary peritoneal cancer with a certain type of abnormal BRCA gene or a positive laboratory tumor test for genomic instability called HRD. LYNPARZA is used in combination with another anti-cancer medicine, bevacizumab, as maintenance treatment after the cancer has responded to your first treatment with platinum-based chemotherapy. Your healthcare provider will perform a test to make sure that LYNPARZA is right for you ovarian cancer, fallopian tube cancer, or primary peritoneal cancer, as maintenance treatment, when the cancer has come back. LYNPARZA is used after the cancer has responded to treatment with platinum-based chemotherapy advanced ovarian cancer with a certain type of abnormal inherited BRCA gene, and have received treatment with 3 or more prior types of chemotherapy medicines. Your healthcare provider will perform a test to make sure that LYNPARZA is right for you human epidermal growth factor receptor 2 (HER2)-negative early breast cancer with a certain type of inherited (germline) abnormal BRCA gene. LYNPARZA is given after surgery (treatment after surgery is called adjuvant therapy). You should have received chemotherapy medicines before or after surgery to remove the tumor. Your healthcare provider will perform a test to make sure that LYNPARZA is right for you a certain type of abnormal inherited BRCA gene, human epidermal growth factor receptor 2 (HER2)-negative breast cancer that has spread to other parts of the body (metastatic). You should have received chemotherapy medicines, either before or after your cancer has spread. If you have hormone receptor (HR)-positive disease, you should have been treated with hormonal therapy. Your healthcare provider will perform a test to make sure that LYNPARZA is right for you metastatic pancreatic cancer with a certain type of abnormal inherited BRCA gene. LYNPARZA is used as a maintenance treatment after your cancer has not progressed on at least 16 weeks of treatment with platinum-based chemotherapy. Your healthcare provider will perform a test to make sure LYNPARZA is right for you prostate cancer with certain inherited or acquired abnormal genes called homologous recombination repair (HRR genes). LYNPARZA is used when the cancer has spread to other parts of the body (metastatic), and no longer responds to a medical or surgical treatment that lowers testosterone, and has progressed after treatment with enzalutamide or abiraterone. Your healthcare provider will perform a test to make sure LYNPARZA is right for you It is not known if LYNPARZA is safe and effective in children.

PADCEV® (enfortumab vedotin-ejfv) with KEYTRUDA® (pembrolizumab)

Seagen and Astellas Announce Positive Topline Results For PADCEV® (enfortumab vedotin-ejfv) with KEYTRUDA® (pembrolizumab) as First-Line Treatment for Advanced Urothelial Cancer

07/26/2022

– Companies plan to discuss results with regulatory authorities –

BOTHELL, Wash. & TOKYO--(BUSINESS WIRE)-- Seagen Inc. (Nasdaq:SGEN) and Astellas Pharma Inc. (TSE:4503, President and CEO: Kenji Yasukawa, Ph.D., “Astellas”) today announced positive topline results from the phase 1b/2 EV-103 clinical trial (also known as KEYNOTE-869) Cohort K evaluating PADCEV® (enfortumab vedotin-ejfv) in combination with Merck’s anti-PD-1 therapy KEYTRUDA® (pembrolizumab) as first-line treatment in patients with unresectable locally advanced or metastatic urothelial cancer (la/mUC) who are ineligible to receive cisplatin-based chemotherapy. Merck is known as MSD outside the United States and Canada.

This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20220726005377/en/

In patients treated with enfortumab vedotin and pembrolizumab, results demonstrated a 64.5% confirmed objective response rate (ORR) (95% CI: 52.7 to 75.1) per blinded independent central review (BICR), the primary endpoint of Cohort K. The median duration of response (DOR) per BICR was not reached. The most frequently reported treatment-emergent adverse events Grade 3 or greater that occurred in more than 5% of patients were rash maculo-papular, anemia, lipase increased, urinary tract infection, hyperglycemia, fatigue, neutropenia, hematuria, diarrhea, acute kidney injury, hyponatremia, chronic kidney disease, weight decreased, syncope, hypophosphatemia, pneumonitis, sepsis, and alanine aminotransferase increased. Overall, the results are generally consistent with previously reported efficacy and safety results of the EV-103 dose-escalation cohort and expansion Cohort A.1 Additional Cohort K results will be reported at an upcoming scientific congress.

EV-103 Cohort K is a randomized cohort investigating enfortumab vedotin alone or in combination with pembrolizumab as first-line treatment in patients with unresectable la/mUC who are ineligible to receive cisplatin-based chemotherapy. Secondary endpoints include ORR per investigator assessment; DOR, disease control rate and progression-free survival per BICR and investigator assessment; overall survival; and assessment of safety.

Please see Important Safety Information at the end of this press release, including BOXED WARNING for enfortumab vedotin.

“We are encouraged by the positive topline results of Cohort K for the combination of enfortumab vedotin and pembrolizumab in first-line locally advanced or metastatic urothelial cancer, and we look forward to sharing results at an upcoming medical meeting,” said Roger Dansey, M.D., interim CEO and Chief Medical Officer, Seagen.

“Approximately half of patients with advanced urothelial carcinoma are ineligible for cisplatin-based chemotherapy,” said Ahsan Arozullah, M.D., M.P.H., Senior Vice President and Head of Development Therapeutic Areas, Astellas. “We intend to discuss Cohort K results with regulatory authorities as we seek to develop a new first-line treatment combination for these patients.”

Seagen, Astellas and Merck are investigating enfortumab vedotin plus pembrolizumab as part of an extensive collaboration, which also includes three Phase 3 studies: the EV-302/KEYNOTE-A39 trial intended to confirm these results, as well as EV-304/KEYNOTE-B15 and EV-303/KEYNOTE-905 in muscle-invasive bladder cancer.

In February 2020, the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy designation for enfortumab vedotin in combination with pembrolizumab for patients with unresectable la/mUC who are ineligible to receive cisplatin-based chemotherapy in the first-line setting. The designation is based on results from the dose-escalation cohort and expansion Cohort A of the phase 1b/2 trial, EV-103 (NCT03288545), evaluating patients with la/mUC who are ineligible to receive cisplatin-based chemotherapy treated in the first-line setting with enfortumab vedotin in combination with pembrolizumab.

About the EV-103 Trial (Cohort K)

The EV-103 trial (NCT03288545) is an ongoing, multi-cohort, open-label, multicenter phase 1b/2 trial of enfortumab vedotin alone or in combination with pembrolizumab and/or chemotherapy in first- or second-line settings in patients with locally advanced or metastatic urothelial cancer (la/mUC) and in patients with muscle-invasive bladder cancer.

Cohort K of the EV-103 trial is investigating enfortumab vedotin alone (n=73) or in combination with pembrolizumab (n=76) in adult patients with unresectable la/mUC who are ineligible for cisplatin-based chemotherapy and have received no prior treatment for la/mUC. The enfortumab vedotin monotherapy study arm is intended to characterize the activity of enfortumab vedotin alone in this patient population. Key outcome measures of EV-103 Cohort K are objective response rate (ORR) per blinded independent central review (BICR) using RECIST 1.1 and assessment of safety.

About PADCEV

PADCEV (enfortumab vedotin-ejfv) is a first-in-class antibody-drug conjugate (ADC) that is directed against Nectin-4, a protein located on the surface of cells and highly expressed in bladder cancer.5 Nonclinical data suggest the anticancer activity of PADCEV is due to its binding to Nectin-4 expressing cells followed by the internalization and release of the anti-tumor agent monomethyl auristatin E (MMAE) into the cell, which result in the cell not reproducing (cell cycle arrest) and in programmed cell death (apoptosis).6

Indication

PADCEV® is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer (mUC) who:

have previously received a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor and platinum-containing chemotherapy, or
are ineligible for cisplatin-containing chemotherapy and have previously received one or more prior lines of therapy.5
https://www.padcev.com/

About Seagen

About Astellas

About the Seagen, Astellas and Merck Collaboration

View source version on businesswire.com: https://www.businesswire.com/news/home/20220726005377/en/

Source: Seagen Inc.

Astellas/Seagen, Merck drug combo shows promise in bladder cancer subtype in trial

Jul. 26, 2022 5:14 AM ET

Seagen Inc. (SGEN), ALPMY, MRK, ALPMF

By: Ravikash, SA News Editor1 Comment

Astellas Pharma (OTCPK:ALPMY) (OTCPK:ALPMF) and Seagen (NASDAQ:SGEN) said Cohort K of a phase 1b/2 trial of their drug Padcev in combination with Merck's (NYSE:MRK) Keytruda showed response in certain patients with a type of bladder cancer.

https://seekingalpha.com/news/3860353-astellasseagen-merck-drug-combo-shows-promise-in-bladder-cancer-subtype-in-trial

https://seekingalpha.com/symbol/ALPMY

https://seekingalpha.com/symbol/ALPMF

https://seekingalpha.com/symbol/SGEN

https://seekingalpha.com/symbol/MRK

https://www.padcev.com/

ENHERTU® (fam-trastuzumab deruxtecan-nxki)

PADCEV® (enfortumab vedotin-ejfv) with KEYTRUDA® (pembrolizumab)

https://www.enhertu.com/en

AstraZeneca, Daiichi Sankyo's Enhertu gets FDA priority review for breast cancer subtype

Jul. 25, 2022 5:10 AM ET

AstraZeneca PLC (AZN), DSKYF, DSNKY

By: Ravikash, SA News Editor

The U.S. Food and Drug Administration (FDA) granted priority review to AstraZeneca (NASDAQ:AZN) and Daiichi Sankyo's (OTCPK:DSKYF) (OTCPK:DSNKY) Enhertu to treat adult patients with unresectable or metastatic HER2-low (immunohistochemistry (IHC) 1+ or IHC 2+/in-situ hybridization (ISH)-negative) breast cancer who have received a prior therapy in the metastatic setting.
https://seekingalpha.com/news/3859868-astrazeneca-daiichi-sankyos-enhertu-gets-fda-priority-review-for-breast-cancer-subtype
https://seekingalpha.com/symbol/AZN
https://seekingalpha.com/symbol/DSKYF
https://seekingalpha.com/symbol/DSNKY
https://www.astrazeneca.com/
https://www.enhertu.com/en

What is ENHERTU? ENHERTU (en-HER-too) is a prescription medicine used in adults to treat human epidermal growth factor receptor 2 (HER2)-positive: Breast cancer that cannot be removed by surgery or that has spread to other parts of the body (metastatic), and who have received a prior anti-HER2 breast cancer treatment: for metastatic disease, or have breast cancer that has come back during or within 6 months of completing treatment for their early-stage breast cancer. Stomach cancer called gastric or gastroesophageal junction (GEJ) adenocarcinoma that has spread to areas near your stomach (locally advanced) or that has spread to other parts of your body (metastatic), and who have received a prior trastuzumab-based regimen. It is not known if ENHERTU is safe and effective in children.

Opdualag™ (nivolumab and relatlimab-rmbw)

PADCEV® (enfortumab vedotin-ejfv) with KEYTRUDA® (pembrolizumab)

Opdualag™ (nivolumab and relatlimab-rmbw)

Bristol Myers Squibb Receives Positive CHMP Opinion Recommending Approval for LAG-3-Blocking Antibody Combination Opdualag (nivolumab and relatlimab) for Treatment of Patients with Unresectable or Metastatic Melanoma

07/22/2022CATEGORY

seeking biotech alpha is biotecMAX 生物技术最大 10/2/2022 the heart of biotech

BIOTECNOVA™

COVID-19 early treatment: real-time analysis of 1,157 studies

BIOTECNOVA™ -Second Group Page

BIOTECNOVA™ -First Group Page

BIOTECNOVA™

DUPIXENT® (DUPILUMAB)

DUPIXENT® (DUPILUMAB)

DUPIXENT® (DUPILUMAB)

DUPIXENT® (DUPILUMAB)

DUPIXENT® (DUPILUMAB)

DUPIXENT® (DUPILUMAB) APPROVED BY FDA AS THE FIRST AND ONLY TREATMENT INDICATED FOR PRURIGO NODULARIS

Sanofi, Regeneron win FDA label expansion for Dupixent in chronic, skin condition

BIOTECNOVA™

KEYTRUDA® (pembrolizumab)

LYNPARZA® (olaparib) tablets

LYNPARZA® (olaparib) tablets

Merck’s KEYTRUDA® (pembrolizumab) Receives Four New Approvals in Japan, Including in High-Risk Early-Stage Triple-Negative Breast Cancer (TNBC)

Merck wins four new approvals for Keytruda in Japan

LYNPARZA® (olaparib) tablets

LYNPARZA® (olaparib) tablets

LYNPARZA® (olaparib) tablets

Lynparza approved in China as 1st-line maintenance treatment with bevacizumab for HRD-positive advanced ovarian cancer

One in two women with advanced ovarian cancer has an HRD-positive tumour

AstraZeneca/Merck's Lynparza gets approval in China for ovarian cancer subtype

ZEJULA (niraparib) capsules

LYNPARZA® (olaparib) tablets

ZEJULA (niraparib) capsules

Oncologic Drugs Advisory Committee to review Zejula overall survival data from the NOVA phase III trial in recurrent ovarian cancer

FDA panel to review GSK Zejula's overall survival data in recurrent ovarian cancer

Retevmo® (selpercatinib)

TUKYSA® (tucatinib) in Combination with Trastuzumab

ZEJULA (niraparib) capsules

FDA Approves Lilly's Retevmo® (selpercatinib), the First and Only RET Inhibitor for Adults with Advanced or Metastatic Solid Tumors with a RET Gene Fusion, Regardless of Type

Eli Lilly wins FDA approval for solid tumor therapy

TUKYSA® (tucatinib) in Combination with Trastuzumab

TUKYSA® (tucatinib) in Combination with Trastuzumab

TUKYSA® (tucatinib) in Combination with Trastuzumab

Seagen Announces TUKYSA® (tucatinib) in Combination with Trastuzumab Granted Priority Review by FDA for Previously Treated HER2-Positive Metastatic Colorectal Cancer

Seagen's application seeking nod for colon cancer combo treatment gets FDA priority review

Veklury® (Remdesivir)

TUKYSA® (tucatinib) in Combination with Trastuzumab

TUKYSA® (tucatinib) in Combination with Trastuzumab

CHMP Adopts Positive Opinion to Extend Indication of Veklury® (Remdesivir) for the Treatment of Pediatric Patients with COVID-19

Gilead's COVID drug Veklury, cancer therapy Yescarta get EMA panel backing for expanded use

YESCARTA® (axicabtagene ciloleucel)

YESCARTA® (axicabtagene ciloleucel)

YESCARTA® (axicabtagene ciloleucel)

Kite’s CAR T-cell Therapy Yescarta® First in Europe to Receive Positive CHMP Opinion for Use in Second-line Diffuse Large B-cell Lymphoma and High-grade B-cell Lymphoma

Gilead's COVID drug Veklury, cancer therapy Yescarta get EMA panel backing for expanded use

OPDIVO® (nivolumab)

YESCARTA® (axicabtagene ciloleucel)

YESCARTA® (axicabtagene ciloleucel)

Bristol Myers Squibb Announces Adjuvant Treatment with Opdivo (nivolumab) Demonstrated Statistically Significant and Clinically Meaningful Improvement in Recurrence-Free Survival (RFS) in Patients with Stage IIB/C Melanoma in the CheckMate -76K Trial

Bristol Myers Opdivo shows survival benefit as adjuvant therapy for skin cancer in trial

KEYTRUDA® (pembrolizumab)

YESCARTA® (axicabtagene ciloleucel)

PADCEV® (enfortumab vedotin-ejfv) With KEYTRUDA® (pembrolizumab)

Health Canada Approves KEYTRUDA® (pembrolizumab) as Adjuvant Treatment for Adults and Children with Stage IIB or IIC Melanoma Following Complete Resection

Merck's Keytruda gets approval in Canada for certain skin cancer patients following surgery

PADCEV® (enfortumab vedotin-ejfv) With KEYTRUDA® (pembrolizumab)

PADCEV® (enfortumab vedotin-ejfv) With KEYTRUDA® (pembrolizumab)

PADCEV® (enfortumab vedotin-ejfv) With KEYTRUDA® (pembrolizumab)

Seagen, Astellas and Merck Announce Results of Clinical Trial Investigating PADCEV® (enfortumab vedotin-ejfv) With KEYTRUDA® (pembrolizumab) and PADCEV as Monotherapy in First-Line Advanced Urothelial Cancer

Seagen, Astellas and Merck Announce Results of Clinical Trial Investigating PADCEV® (enfortumab vedotin-ejfv) with KEYTRUDA® (pembrolizumab) and PADCEV as Monotherapy in First-Line Advanced Urothelial Cancer

Astellas/Seagen, Merck Padcev/Keytruda combo shows promise in urothelial cancer in trial

RUBRACA® (rucaparib) tablets

PADCEV® (enfortumab vedotin-ejfv) With KEYTRUDA® (pembrolizumab)

ENHERTU® (fam-trastuzumab deruxtecan-nxki) for injection

Clovis Oncology’s Rubraca® (Rucaparib) As First-Line Maintenance Treatment Improves Progression-Free Survival In Women With Advanced Ovarian Cancer Across Disease Risk Subgroups

Clovis stock rises 15% as Rubraca shows survival benefit as maintenance therapy for ovarian cancer in trial

ENHERTU® (fam-trastuzumab deruxtecan-nxki) for injection

PADCEV® (enfortumab vedotin-ejfv) With KEYTRUDA® (pembrolizumab)

ENHERTU® (fam-trastuzumab deruxtecan-nxki) for injection

Enhertu continues to demonstrate clinically meaningful tumour response in patients with HER2-mutant metastatic non-small cell lung cancer

11 September 2022 09:15 BST

AstraZeneca, Daiichi Sankyo's Enhertu shows response in lung cancer patients in trial

BIOTECNOVA™

Imfinzi (durvalumab) and tremelimumab with chemotherapy

Imfinzi (durvalumab) and tremelimumab with chemotherapy

HIMALAYA Phase III trial exploratory results support the benefit of tremelimumab
added to Imfinzi in unresectable liver cancer regardless of aetiology

Approval based on TOPAZ-1 Phase III trial results, which showed Imfinzi
combination reduced risk of death by 20% vs. chemotherapy alone

Forxiga approved in China for the treatment of chronic kidney disease in patients at risk of progression with and without
type-2 diabetes

Approval marks the first SGLT2 inhibitor approved in China for chronic kidney
disease in adult patients with and without type-2 diabetes

First and only approved medicine targeting
BRCA mutations in early breast cancer