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DUPIXENT® (DUPILUMAB)
ENHERTU® (fam-trastuzumab deruxtecan-nxki) for injection
DUPIXENT® (DUPILUMAB)
January 30, 2023 at 1:00 AM EST
DUPIXENT® (DUPILUMAB) APPROVED BY EUROPEAN COMMISSION AS THE FIRST AND ONLY TARGETED MEDICINE INDICATED FOR EOSINOPHILIC ESOPHAGITIS
Approximately 60% of patients aged 12 years and older treated with Dupixent 300 mg weekly in the pivotal trial experienced histological disease remission; patients also significantly improved their ability to swallow compared to placebo
Dupixent is now an option for the approximately 50,000 adults and adolescents living with severe uncontrolled eosinophilic esophagitis in the European Union (EU)
Dupixent now approved to treat five diseases with underlying type 2 inflammation in the EU
TARRYTOWN, N.Y. and PARIS, Jan. 30, 2023 (GLOBE NEWSWIRE) -- Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) and Sanofi today announced that the European Commission (EC) expanded the marketing authorization for Dupixent® (dupilumab) in the European Union (EU) to treat eosinophilic esophagitis (EoE) in adults and adolescents 12 years and older, weighing at least 40 kg, who are inadequately controlled by, are intolerant to, or who are not candidates for conventional medicinal therapy. EoE is a chronic, progressive inflammatory disease that damages the esophagus and prevents it from working properly. With this approval, Dupixent is the first and only targeted medicine specifically indicated to treat EoE in Europe and the U.S.
“This latest approval establishes Dupixent as the only targeted medicine specifically indicated for eosinophilic esophagitis in the European Union. Dupixent is also the only biologic shown in pivotal trials to help patients achieve histological remission, reduce difficulty swallowing and improve health-related quality of life – all of which are crucial to reducing the burden of this debilitating disease,” said George D. Yancopoulos, M.D., Ph.D., President and Chief Scientific Officer at Regeneron, and a principal inventor of Dupixent. “Since its first approval, Dupixent has redefined the treatment of certain chronic diseases with underlying type 2 inflammation and is now indicated for five conditions in the European Union. We remain committed to investigating Dupixent’s potential in additional diseases in which IL-4 and IL-13 may play a key role.”
“The impact of EoE on a patient’s daily life cannot be overstated – the narrowing and scarring of the esophagus can make something as simple as eating a painful and distressing experience, and may lead to choking and food impaction,” said Naimish Patel, M.D., Head of Global Development, Immunology and Inflammation at Sanofi. “With this latest approval for Dupixent, adults and adolescents in the EU suffering from the chronic and often debilitating symptoms of EoE now have the first and only targeted treatment option clinically proven to reduce both esophageal inflammation and damage, as well as improve swallowing ability, pain and health-related quality of life.”
The EC decision is supported by 52-week data from a Phase 3 trial consisting of three parts (Part A, B and C). Part A and Part B investigated Dupixent 300 mg weekly (Part A n=42; Part B n=80) compared to placebo (Part A n=39; Part B n=79) for 24 weeks. Part C (n=188) observed patients who had continued on or switched to Dupixent from Parts A and B for an additional 28 weeks.
Dupixent patients in Parts A and B, respectively, experienced:
- An approximately 10 times higher rate of histological disease remission (60% and 59%), a co-primary endpoint, compared to placebo (5% and 6%).
- A 69% and 64% reduction in disease symptoms compared to 32% and 41% with placebo. Disease symptoms were measured using the Dysphagia Symptom Questionnaire (DSQ), on which Dupixent patients experienced a 21.9- and 23.8-point clinically meaningful improvement compared to a 9.6- and 13.9-point improvement for placebo, a co-primary endpoint. Swallowing improvement was observed as early as four weeks.
- A greater than seven-fold reduction in abnormal endoscopic findings from baseline (-3.2 and -4.5 points) compared to placebo (-0.3 and -0.6 points).
- Nominally significant improvements in swallowing-related pain and health-related quality of life, as well as less frequent non-swallowing symptoms.
Histological disease remission, swallowing improvement and reduction in abnormal endoscopic findings were consistent with the overall population in patients who were uncontrolled, or not responsive to or not eligible for swallowed topical corticosteroids. Longer term efficacy in Part C was similar to results observed in Parts A and B.
The safety results of the trial were generally consistent with the known safety profile of Dupixent in its approved indications. The most common side effects across indications were injection site reactions, conjunctivitis, conjunctivitis allergic, arthralgia, oral herpes and eosinophilia. Adverse events more commonly observed in EoE patients treated with Dupixent (n=122) compared to placebo (n=117) included infections (32% vs. 25%). An additional adverse reaction of injection site bruising was reported in the EoE trial. The safety profile through 52 weeks was generally consistent with the safety profile observed at 24 weeks.
About the Dupixent Eosinophilic Esophagitis Trial
The three-part Phase 3 randomized, double-blind, placebo-controlled trial evaluated the efficacy and safety of Dupixent in patients aged 12 years and older with EoE. All patients had previously not responded to proton pump inhibitors, and, across Parts A and B, 74% of patients were previously treated with swallowed topical corticosteroids.
At 24 weeks, the co-primary endpoints in Parts A and B assessed patient-reported measures of difficulty swallowing (change from baseline in the DSQ on a 0-84 scale) and esophageal inflammation (proportion of patients achieving histological disease remission, defined as peak esophageal intraepithelial eosinophil count of ≤6 eos/hpf).
Additional endpoints included abnormal endoscopic findings (EoE Endoscopic Reference Score [EoE-EREFS] on a 0-18 scale), swallowing-related pain (DSQ pain score), health-related quality of life (EoE Impact Questionnaire [EoE-IQ]) and frequency of other non-dysphagia symptoms (EoE Symptom Questionnaire [EoE-SQ]).
About Dupixent
Dupixent is an injection administered under the skin (subcutaneous injection) at different injection sites. In the EU for adolescents and adults with EoE, Dupixent is administered at 300 mg every week. It is available as both a pre-filled pen and pre-filled syringe at the 300 mg 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.
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 atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP), prurigo nodularis and EoE.
Dupixent has received regulatory approvals in one or more countries around the world for use in certain patients with atopic dermatitis, asthma, CRSwNP, EoE or prurigo nodularis in different age populations. Dupixent is currently approved for one or more of these indications in more than 60 countries, including in Europe, the U.S. and Japan. More than 500,000 patients have been treated with Dupixent globally.
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 a substantial proportion 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 EoE, hand and foot atopic dermatitis, chronic inducible urticaria-cold, chronic spontaneous urticaria, chronic pruritus 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 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.
Please see accompanying full Prescribing Information including Patient Information.
About Regeneron
Regeneron (NASDAQ: REGN) is a leading biotechnology company that invents, develops and commercializes life-transforming medicines for people with serious diseases. Founded and led for 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.
Source: Regeneron Pharmaceuticals, Inc.
Sanofi, Regeneron Dupixent gets approval in EU for expanded use in eosinophilic esophagitis
Jan. 30, 2023 4:26 AM ET
By: Ravikash, SA News Editor
The European Commission (EC) approved Sanofi (NASDAQ:SNY) and Regeneron Pharmaceuticals' (NASDAQ:REGN) Dupixent to treat eosinophilic esophagitis (EoE) in patients 12 years and older, weighing at least 40 kg, who are inadequately controlled by, are intolerant to, or who are not eligible for conventional medicinal therapy.
ENHERTU® (fam-trastuzumab deruxtecan-nxki) for injection
DUPIXENT® (DUPILUMAB)
ENHERTU® (fam-trastuzumab deruxtecan-nxki) for injection
ENHERTU® (fam-trastuzumab deruxtecan-nxki) for injection
ENHERTU® (fam-trastuzumab deruxtecan-nxki) for injection
Enhertu approved in the EU as the first HER2-directed therapy for patients with HER2-low metastatic breast cancer
PUBLISHED26 January 2023 26 January 2023 07:00 GMT
Approval based on DESTINY-Breast04 results where AstraZeneca and Daiichi Sankyo’s Enhertu reduced the risk of disease progression or death by 50% and increased overall survival by more than 6 months vs. chemotherapy
AstraZeneca and Daiichi Sankyo’s Enhertu (trastuzumab deruxtecan) has been approved in the European Union (EU) as monotherapy for the treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer who have received prior chemotherapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy.
Enhertu is a specifically engineered HER2-directed antibody drug conjugate (ADC) being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.
The approval by the European Commission follows the positive opinion of the Committee for Medicinal Products for Human Use and is based on results from the DESTINY-Breast04 Phase III trial, which were presented at the American Society of Clinical Oncology 2022 Annual Meeting and published in The New England Journal of Medicine.1
In the trial, Enhertu significantly reduced the risk of disease progression or death by 50% versus physician’s choice of chemotherapy (based on a hazard ratio [HR] of 0.50; 95% confidence interval [CI]: 0.40-0.63; p<0.0001) in patients with HER2-low metastatic breast cancer with hormone receptor (HR)-positive or HR-negative disease. A median progression-free survival (PFS) of 9.9 months was seen with Enhertu versus 5.1 months in those treated with chemotherapy, as assessed by blinded independent central review (BICR). A 36% reduction in the risk of death was seen with Enhertu compared to chemotherapy (hazard ratio of 0.64; 95% CI: 0.49-0.84; p=0.001) with a median overall survival (OS) of 23.4 months versus 16.8 months.
Javier Cortés, MD, PhD, Head, International Breast Cancer Center, Barcelona, Spain, said: “The European approval of Enhertu in the HER2-low metastatic breast cancer population marks the first time we will have the opportunity to treat patients with lower levels of HER2 expression with a HER2-directed therapy. Enhertu has shown a significant improvement in outcomes compared to chemotherapy for these patients, reinforcing its potential to become a new standard of care.”
Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: “Historically, patients with breast cancer who have tumours with low levels of HER2 expression have been classified as HER2-negative, giving them limited treatment options beyond chemotherapy. This approval reinforces the important role Enhertu may have for patients with HER2-low disease and highlights the need to evolve the way breast cancer is treated to improve patient outcomes.”
Ken Keller, Global Head of Oncology Business, and President and CEO, Daiichi Sankyo, Inc, said: “The approval of Enhertu in HER2-low metastatic breast cancer represents a significant clinical advance for patients in Europe with both HR-positive and HR-negative disease who previously have had limited treatment options in the late-line setting. This milestone also supports our vision to bring Enhertu to more patients across the HER2 spectrum, which requires a change to the breast cancer classification system that has been guiding treatment for more than two decades.”
The safety profile observed in patients treated with Enhertu in the DESTINY-Breast04 trial was consistent with that seen in other trials of Enhertu in breast cancer with no new safety signals identified.
Financial considerations
Following EU approval, an amount of $150m is due from AstraZeneca to Daiichi Sankyo as a milestone payment for this HER2-low breast cancer post-chemotherapy indication. The milestone payment will be capitalised as an addition to the upfront payment made by AstraZeneca to Daiichi Sankyo in 2019 and subsequent capitalised milestones.
Sales of Enhertu in most EU territories are recognised by Daiichi Sankyo. AstraZeneca reports its share of gross profit margin from Enhertu sales in those territories as collaboration revenue in the Company’s financial statements. AstraZeneca will record product sales in respect of sales made in territories where AstraZeneca is the selling party.
Further details on the financial arrangements were set out in the March 2019 announcement of the collaboration.
DESTINY-Breast04
DESTINY-Breast04 is a global, randomised, open-label, Phase III trial evaluating the efficacy and safety of Enhertu (5.4mg/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 randomised 2:1 to receive either Enhertu or chemotherapy.
The primary endpoint of DESTINY-Breast04 is PFS in patients with HR-positive disease based on BICR. Key secondary endpoints include PFS based on BICR in all randomised patients (HR-positive and HR-negative disease), OS in patients with HR-positive disease and OS in all randomised 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.
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 40 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 more than 30 countries 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 systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results of 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 non-small cell lung cancer 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. 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 more than 30 countries for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 trial and/or DESTINY-Gastric02 trials.
Enhertu development programme
A comprehensive global development programme 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, are also underway.
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 (DS-1062; 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 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.
With Enhertu (trastuzumab deruxtecan), a HER2-directed ADC, AstraZeneca and Daiichi Sankyo are aiming to improve outcomes in previously treated HER2-positive and HER2-low metastatic breast cancer and are exploring its potential in earlier lines of treatment and in new breast cancer settings.
In HR-positive breast cancer, AstraZeneca continues to improve outcomes with foundational medicines Faslodex (fulvestrant) and Zoladex (goserelin) and aims to reshape the HR-positive space with next-generation SERD and potential new medicine camizestrant as well as a potential first-in-class AKT kinase inhibitor, capivasertib. AstraZeneca is also collaborating with Daiichi Sankyo to explore the potential of TROP2-directed ADC, datopotamab deruxtecan, in this setting.
PARP inhibitor Lynparza (olaparib) is a targeted treatment option that has been studied in early and metastatic breast cancer with an inherited BRCA mutation. AstraZeneca with MSD (Merck & Co., Inc. in the US and Canada) continue to research Lynparza in these settings and to explore its potential in earlier disease.
To bring much-needed treatment options to patients with triple-negative breast cancer, an aggressive form of breast cancer, AstraZeneca is evaluating the potential of datopotamab deruxtecan alone and in combination with immunotherapy Imfinzi (durvalumab), capivasertib in combination with chemotherapy, and Imfinzi in combination with other oncology medicines, including Lynparza and Enhertu.
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.
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 gets approval in EU for breast cancer subtype
Jan. 26, 2023 4:36 AM ET
AstraZeneca PLC (AZN), DSKYF, DSNKY
By: Ravikash, SA News Editor
- The European Commission (EC) approved AstraZeneca (NASDAQ:AZN) and Daiichi Sankyo's (OTCPK:DSKYF) (OTCPK:DSNKY) drug Enhertu to treat certain patients with a type of breast cancer.
- https://seekingalpha.com/news/3928225-astrazeneca-daiichi-sankyos-enhertu-gets-approval-in-eu-for-breast-cancer-subtype
- AstraZeneca PLC (AZN), DSKYF, DSNKY
- https://enhertu.com/en
- https://www.astrazeneca.com/
KEYTRUDA® (pembrolizumab) Plus Chemotherapy
TUKYSA® (tucatinib) in Combination with Trastuzumab
ENHERTU® (fam-trastuzumab deruxtecan-nxki) for injection
Merck’s KEYTRUDA® (pembrolizumab) Plus Chemotherapy Significantly Improved Overall Survival Versus Chemotherapy in First-Line Advanced or Unresectable Biliary Tract Cancer in KEYNOTE-966 Trial
January 25, 2023 6:45 am ET
RAHWAY, N.J.--(BUSINESS WIRE)-- Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced positive results from the Phase 3 KEYNOTE-966 trial. In the final analysis of this trial, KEYTRUDA, Merck’s anti-PD-1 therapy, in combination with standard of care chemotherapy (gemcitabine and cisplatin) demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) versus chemotherapy alone for the first-line treatment of patients with advanced or unresectable biliary tract cancer (BTC). The safety profile of KEYTRUDA in this trial was consistent with that observed in previously reported studies. Results will be presented at an upcoming medical meeting and will be submitted to regulatory authorities.
“Biliary tract cancer is typically diagnosed at an advanced stage, and these patients face a poor prognosis, with five-year survival rates estimated to be approximately 5% to 15%,” said Dr. Eliav Barr, senior vice president, head of global clinical development and chief medical officer, Merck Research Laboratories. “We are very encouraged by these overall survival results that show the potential benefit of KEYTRUDA in addition to chemotherapy for biliary cancer patients who are in urgent need of new treatment options.”
Merck has an extensive clinical development program evaluating KEYTRUDA in gastrointestinal cancers and is continuing to study KEYTRUDA for multiple uses in gastric, hepatobiliary, esophageal, pancreatic and colorectal cancers.
About KEYNOTE-966
KEYNOTE-966 is a randomized, double-blind Phase 3 trial (ClinicalTrials.gov, NCT04003636) evaluating KEYTRUDA in combination with gemcitabine and cisplatin compared to placebo plus gemcitabine and cisplatin for the first-line treatment of advanced and/or unresectable BTC. The primary endpoint was OS, and the secondary endpoints included progression-free survival, objective response rate, duration of response and safety. The trial enrolled 1,069 patients who were randomized to receive KEYTRUDA (200 mg every three weeks for up to approximately two years) plus gemcitabine and cisplatin, or placebo plus gemcitabine and cisplatin.
About Biliary Tract Cancer (BTC)
Biliary tract cancer is a group of rare and highly aggressive cancers in the gallbladder and bile ducts. Biliary tract cancer is the second most common type of primary liver cancer after hepatocellular carcinoma, accounting for 15% of all liver cancers. It is estimated there are approximately 211,000 new cases of BTC diagnosed and 174,000 deaths from the disease each year globally. Biliary tract cancer is most frequently diagnosed in patients between 50 to 70 years old, and 70% of BTC patients are diagnosed at an advanced stage. Patients diagnosed with BTC face a very poor prognosis, as the five-year survival rate is estimated to be between 5% and 15%.
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.
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 MSI-H central nervous system cancers have not been established.
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.
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's Keytruda shows survival benefit in biliary tract cancer, meeting phase 3 study goal
Jan. 25, 2023 7:50 AM ET
By: Ravikash, SA News Editor
Merck's (NYSE:MRK) Keytruda, with standard of care chemotherapy, met the main goal of overall survival (OS) in patients with advanced or unresectable biliary tract cancer (BTC) in a phase 3 trial.
FDA Approves KEYTRUDA® (pembrolizumab) as Adjuvant Treatment Following Surgical Resection and Platinum-Based Chemotherapy for Patients With Stage IB (T2a ≥4 Centimeters), II, or IIIA Non-Small Cell Lung Cancer (NSCLC)
January 27, 2023 6:45 am ET
Approval based on KEYNOTE-091 trial, which demonstrated a clinically meaningful improvement in disease-free survival with KEYTRUDA in these patients following surgical resection and platinum-based chemotherapy versus placebo
Approval marks fifth indication for KEYTRUDA-based regimens in NSCLC and 34th indication for KEYTRUDA in the US
RAHWAY, N.J.--(BUSINESS WIRE)-- Merck (NYSE: MRK), known as MSD outside of the United States and Canada, announced today that the U.S. Food and Drug Administration (FDA) has approved KEYTRUDA, Merck’s anti-PD-1 therapy, as a single agent, for adjuvant treatment following surgical resection and platinum-based chemotherapy for adult patients with stage IB (T2a ≥4 centimeters [cm]), II, or IIIA non-small cell lung cancer (NSCLC).
JARDIANCE® (empagliflozin tablets)
TUKYSA® (tucatinib) in Combination with Trastuzumab
TUKYSA® (tucatinib) in Combination with Trastuzumab
US FDA accepts supplemental New Drug Application for Jardiance® for adults with chronic kidney disease
January 20, 2023
The supplemental New Drug Application is based on results from the landmark EMPA-KIDNEY phase III trial, which showed Jardiance® (empagliflozin) tablets significantly reduced the risk of kidney disease progression* or cardiovascular death in adults with CKD by 28% (absolute risk reduction [ARR]: 3.8%) compared with placebo, both on top of standard of care.
RIDGEFIELD, Conn. and INDIANAPOLIS, Jan. 20, 2023 /PRNewswire/ -- The U.S. Food and Drug Administration (FDA) has accepted a supplemental New Drug Application (sNDA) for Jardiance® (empagliflozin) tablets, which is being investigated as a potential treatment to reduce the risk of kidney disease progression and cardiovascular death in adults with chronic kidney disease (CKD), Boehringer Ingelheim and Eli Lilly and Company (NYSE: LLY) announced.
"There is a significant need for additional therapies that reduce the risk of kidney disease progression and hospitalizations in adults with CKD," said Mohamed Eid, M.D., M.P.H., M.H.A., vice president, Clinical Development & Medical Affairs, Cardio-Renal-Metabolism & Respiratory Medicine, Boehringer Ingelheim Pharmaceuticals, Inc. "This application acceptance is an important step forward for the approximately 37 million people in the U.S. living with CKD."
The sNDA is based on results from the landmark EMPA-KIDNEY phase III trial, in which Jardiance significantly reduced the risk of kidney disease progression* or cardiovascular death in adults with CKD by 28% (ARR: 3.8%) compared with placebo, both on top of standard of care. Results were presented during the American Society of Nephrology (ASN)'s Kidney Week 2022 and simultaneously published in The New England Journal of Medicine. EMPA-KIDNEY is the first SGLT2 inhibitor CKD trial to show a significant reduction in risk of hospitalization for any cause, with a 14% relative risk reduction with Jardiance versus placebo (24.8 vs. 29.2 events/100 patient-years, respectively), both on top of standard of care, in a pre-specified key secondary endpoint. Reductions in other key secondary endpoints of hospitalization for heart failure or cardiovascular death or all-cause death were not statistically significant. Hospitalizations account for 35% to 55% of total healthcare costs for people with CKD in the U.S.
EMPA-KIDNEY, the largest and broadest dedicated SGLT2 inhibitor trial in CKD to date, provides additional data for patients commonly seen in clinical practice. The trial enrolled 6,609 participants, including people without diabetes (56%), those with various underlying causes of CKD and those across the spectrum of eGFR and urine albumin-creatinine ratio (measures of kidney function and excess albumin in the urine, respectively). Overall, the safety data in EMPA-KIDNEY were consistent with the previously known safety profile of Jardiance.
Initially approved in 2014, Jardiance is a once-daily tablet used along with diet and exercise to lower blood sugar in adults with type 2 diabetes; and to reduce the risk of cardiovascular death in adults with type 2 diabetes and known cardiovascular disease. Jardiance is also indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in adults with heart failure. Jardiance is not for patients with type 1 diabetes, or to improve glycemic control in adults with type 2 diabetes with an eGFR <30 mL/min/1.73 m2. Jardiance is contraindicated in people with hypersensitivity to empagliflozin or any of the excipients in Jardiance, and in patients on dialysis. Please see additional Important Safety Information below.
"This marks another exciting milestone for Jardiance, potentially extending its ability to positively impact the approximately one billion people diagnosed with a cardio, renal or metabolic condition," said Jeff Emmick, M.D., Ph.D., vice president, Product Development, Lilly. "We look forward to working with the FDA during the review process and eagerly await a decision later this year on the indication for CKD, which doubles a person's risk for hospitalization."
In March 2020, the FDA granted Fast Track designation to the clinical investigation of Jardiance to reduce the risk of kidney disease progression and cardiovascular death in adults with CKD. According to the FDA, Fast Track designation is designed to facilitate the development of drugs and expedite treatments that may address serious conditions and fill an unmet medical need. Jardiance is not indicated for the treatment of CKD.
*Kidney disease progression: Defined as end-stage kidney disease (the initiation of maintenance dialysis or receipt of a kidney transplant), a sustained decline in estimated glomerular filtration rate (eGFR) to below 10 mL/min/1.73 m2, kidney death or a sustained decline of at least 40% in eGFR from randomization).
About EMPA-KIDNEY: The study of heart and kidney protection with Jardiance
EMPA-KIDNEY (NCT03594110) is a multinational, randomized, double-blind, placebo-controlled clinical trial, designed to evaluate the effect of Jardiance on kidney disease progression and cardiovascular mortality risk. The primary outcome is defined as time to a first event of either cardiovascular death or kidney disease progression, defined as end-stage kidney disease (the need for kidney replacement therapy such as dialysis or kidney transplantation), a sustained decline in eGFR to <10 mL/min/1.73 m2, kidney death or a sustained decline of ≥40 percent in eGFR from randomization. Key secondary outcomes include cardiovascular death or hospitalization for heart failure, all-cause hospitalization and all-cause mortality. EMPA-KIDNEY includes 6,609 adults randomized from eight countries with established CKD both with and without diabetes, as well as with and without albuminuria, receiving either Jardiance 10 mg or placebo, on top of current standard of care.
What is JARDIANCE?
JARDIANCE is a prescription medicine used to:
- reduce the risk of cardiovascular death and hospitalization for heart failure in adults with heart failure, when the heart cannot pump enough blood to the rest of your body
- reduce the risk of cardiovascular death in adults with type 2 diabetes who also have known cardiovascular disease
- lower blood sugar along with diet and exercise in adults with type 2 diabetes
JARDIANCE is not for people with type 1 diabetes. It may increase their risk of diabetic ketoacidosis (increased ketones in the blood or urine).
JARDIANCE is not for use to lower blood sugar in adults with type 2 diabetes who have severe kidney problems, because it may not work.
https://www.jardiance.com/type-2-diabetes/
For more information, please see Prescribing Information and Medication Guide.
Boehringer Ingelheim and Eli Lilly and Company
In January 2011, Boehringer Ingelheim and Eli Lilly and Company announced an Alliance that centers on compounds representing several of the largest diabetes treatment classes. Depending on geographies, the companies either co-promote or separately promote the respective molecules each contributing to the Alliance. The Alliance leverages the strengths of two of the world's leading pharmaceutical companies to focus on patient needs. By joining forces, the companies demonstrate their commitment, not only to the care of people with diabetes, but also to investigating the potential to address areas of unmet medical need.
About Boehringer Ingelheim
Boehringer Ingelheim is working on breakthrough therapies that improve the lives of humans and animals. As a leading research-driven biopharmaceutical company, the company creates value through innovation in areas of high unmet medical need. Founded in 1885 and family-owned ever since, Boehringer Ingelheim takes a long-term perspective. Around 52,000 employees serve more than 130 markets in the three business areas, Human Pharma, Animal Health, and Biopharmaceutical Contract Manufacturing. Learn more at www.boehringer-ingelheim.us.
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 and LinkedIn.
This press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about Jardiance® as a treatment for adults with type 2 diabetes, to reduce the risk of cardiovascular death in adults with type 2 diabetes and known cardiovascular disease, and to reduce the risk of cardiovascular death and hospitalization for heart failure in adults with heart failure, and as a potential treatment for adults with cardio-kidney-metabolic conditions and reflects Lilly's current beliefs and expectations. However, as with any pharmaceutical product, there are substantial risks and uncertainties in the process of drug research, development and commercialization. Among other things, there can be no guarantee that planned or ongoing studies will be completed as planned, that future study results will be consistent with the results to date or that Jardiance® will receive additional regulatory approvals. For a further discussion of these and other risks and uncertainties that could cause actual results to differ from Lilly's expectations, please see Lilly's most recent Forms 10-K and 10-Q filed with the U.S. Securities and Exchange Commission. Lilly undertakes no duty to update forward-looking statements.
Jardiance®, EMPEROR-Reduced®, EMPEROR-Preserved®, EMPA-REG OUTCOME® and EMPACT-MI® are registered trademarks of Boehringer Ingelheim.
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SOURCE Eli Lilly and Company
Lilly's diabetes drug Jardiance to get FDA review for chronic kidney disease indication
Jan. 20, 2023 10:02 AM ET
By: Jonathan Block, SA News Editor
- The US FDA has accepted a supplemental New Drug Application for Eli Lilly's Jardiance (empagliflozin) as a treatment to cut the risk of kidney disease progression and cardiovascular death in those with chronic kidney disease (CKD).
- https://seekingalpha.com/news/3926360-lillys-diabetes-drug-jardiance-to-get-fda-review-for-chronic-kidney-disease-indication
- Eli Lilly and Company (LLY)
- https://www.jardiance.com/type-2-diabetes/
- https://www.lilly.com/
TUKYSA® (tucatinib) in Combination with Trastuzumab
TUKYSA® (tucatinib) in Combination with Trastuzumab
TUKYSA® (tucatinib) in Combination with Trastuzumab
Seagen Announces FDA Accelerated Approval of TUKYSA® (tucatinib) in Combination with Trastuzumab for People with Previously Treated RAS Wild-Type, HER2-Positive Metastatic Colorectal Cancer
01/19/2023
– First FDA-approved treatment in HER2-positive metastatic colorectal cancer –
– Combination regimen is approved for use in the second-line treatment setting and beyond –
BOTHELL, Wash.--(BUSINESS WIRE)-- Seagen Inc. (Nasdaq: SGEN) today announced that the U.S. Food and Drug Administration (FDA) has granted accelerated approval to TUKYSA® (tucatinib) in combination with trastuzumab for adult patients with RASwild-type, HER2-positive unresectable or metastatic colorectal cancer that has progressed following treatment with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy. TUKYSA is approved under the FDA’s Accelerated Approval Program based on tumor response rate and durability of response from the phase 2 MOUNTAINEER clinical trial. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. This is the first FDA-approved treatment in HER2-positive metastatic colorectal cancer. The FDA previously granted Breakthrough Therapy Designation and Priority Review for TUKYSA in this setting.
“Historically, patients with HER2-positive metastatic colorectal cancer who have progressed following frontline therapy have had poor outcomes,” said John Strickler, M.D., associate professor of medicine, Duke University Medical Center, and lead investigator for the MOUNTAINEER trial. “The FDA approval of a chemotherapy-free combination regimen that specifically targets HER2 is great news for these patients.”
“Biomarker testing is bringing new hope to people living with some types of colorectal cancer by opening the door to targeted treatments like TUKYSA for those who have RAS wild-type, HER2-positive disease,” said Michael Sapienza, CEO, Colorectal Cancer Alliance. “It is critical that physicians and patients understand the importance of comprehensive biomarker testing at diagnosis because it can inform treatment decisions and help improve outcomes.”
Results from the MOUNTAINEER trial showed a 38% overall response rate (ORR) (95% Confidence Interval [CI]: 28, 49) per blinded independent central review (BICR) in the patients who received TUKYSA in combination with trastuzumab (N=84 with a median age of 55.0 years [range: 24 to 77]). Complete responses were observed in 3.6% of patients (n=3), and partial responses were observed in 35% of patients (n=29). The median duration of response (DOR) per BICR was 12.4 months (95% CI: 8.5, 20.5). At study entry, 64% and 70% of these patients had liver or lung metastases, respectively.
The Prescribing Information for TUKYSA includes warnings and precautions for diarrhea, hepatotoxicity and embryo-fetal toxicity, some of which may be severe or fatal. In MOUNTAINEER, serious adverse reactions occurred in 22% of patients; the most common (in ≥2% of patients) were intestinal obstruction (7%), urinary tract infection (3.5%), pneumonia, abdominal pain and rectal perforation (2.3% each). The most common adverse reactions (≥20%) in patients treated with TUKYSA and trastuzumab were diarrhea, fatigue, rash, nausea, abdominal pain, infusion-related reactions and pyrexia. Adverse reactions leading to permanent discontinuation of TUKYSA occurred in 6% of patients; the most common (in ≥2% of patients) was increased alanine aminotransferase (ALT) (2.3%). Please see additional Important Safety Information below.
“The accelerated approval of TUKYSA for RAS wild-type, HER2-positive metastatic colorectal cancer expands TUKYSA-based therapy to patients across two distinct types of cancer,” said Marjorie Green, M.D., Senior Vice President and Head of Late-Stage Development, Seagen. “We believe the efficacy and safety profile of the TUKYSA and trastuzumab-based regimen further establishes its role as an important backbone of dual HER2 inhibition in the treatment of adult patients with certain HER2-expressing breast and colorectal cancers.”
The FDA’s Accelerated Approval Program allows for approval of a medicine based on a surrogate endpoint that is reasonably likely to predict clinical benefit if the medicine fills an unmet medical need for a serious condition. A global, randomized phase 3 clinical trial (MOUNTAINEER-03) is ongoing and will compare TUKYSA in combination with trastuzumab and mFOLFOX6 with standard of care, which is intended to serve as a confirmatory trial and potentially support future global regulatory submissions. Merck, known as MSD outside of the U.S. and Canada, is commercializing TUKYSA in regions outside of the U.S., Canada and Europe and plans to discuss results from the MOUNTAINEER trial with certain health authorities as it continues to accelerate the filing of TUKYSA in its territories.
About Colorectal Cancer
In the U.S., approximately 153,000 people will be diagnosed with colorectal cancer in 2023, and the rate of the disease is increasing in younger adults.1 Approximately 22% of U.S. patients with colorectal cancer are diagnosed at the advanced stage.2 Human epidermal growth factor receptor 2 (HER2) is overexpressed in 3-5% of patients with metastatic colorectal cancer and approximately 10% of patients with RASwild-type metastatic colorectal cancer.3 In 2023, colorectal cancer is anticipated to lead to about 52,550 deaths in the U.S., where it is the third-leading cause of cancer-related deaths.1
About MOUNTAINEER
MOUNTAINEER is a U.S. and European open-label, multicenter phase 2 clinical trial of TUKYSA in combination with trastuzumab that evaluated 84 patients with HER2-positive, RASwild-type, unresectable or metastatic colorectal cancer following previous standard-of-care therapies. Patients evaluated in MOUNTAINEER had not received prior anti-HER2 therapy. Patients received TUKYSA (300 mg) twice per day orally in combination with trastuzumab intravenously (8 mg/kg loading dose, then 6 mg/kg every three weeks thereafter) until disease progression or unacceptable toxicity. The major efficacy outcome measures were overall response rate (ORR) and duration of response (DOR) as assessed by blinded independent central review (BICR) according to RECIST (Response Evaluation Criteria in Solid Tumors) version 1.1.
About TUKYSA (tucatinib)
TUKYSA (tucatinib) tablets (50 | 150 mg tablets) 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 was approved by the U.S. FDA in April 2020 in combination with trastuzumab and capecitabine for treatment of adult patients with advanced unresectable or metastatic HER2-positive breastcancer, including patients with brain metastases, who have received one or more prior anti-HER2-based regimens in the metastatic setting. In January 2023, TUKYSA received accelerated approval by the U.S. FDA in combination with trastuzumab for adult patients with RASwild-type, HER2-positive unresectable or metastatic colorectal cancer that has progressed following treatment with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy. Merck, known as MSD outside the U.S. and Canada, has exclusive rights to commercialize TUKYSA in Asia, the Middle East and Latin America and other regions outside of the U.S., Canada and Europe.
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.
Seagen wins FDA accelerated approval for colorectal cancer therapy
Jan. 19, 2023 2:37 PM ET
By: Dulan Lokuwithana, SA News Editor1 Comment
- Seagen (NASDAQ:SGEN) announced Thursday that the FDA granted accelerated approval for its tyrosine kinase inhibitor Tukysa, in combination with Roche’s (OTCQX:RHHBY) (OTCQX:RHHBF) trastuzumab for the treatment of certain adults with colorectal cancer as a second-line option.
- https://seekingalpha.com/news/3926075-sgen-stock-gains-fda-clears-colorectal-cancer-therapy
- Seagen Inc. (SGEN), MRK
- https://www.herceptin.com/hcp.html
- https://www.tukysa.com/
- https://www.seagen.com/
TECENTRIQ® (atezolizumab) injection plus AVASTIN® (bevacizumab) injection
TECENTRIQ® (atezolizumab) injection plus AVASTIN® (bevacizumab) injection
TECENTRIQ® (atezolizumab) injection plus AVASTIN® (bevacizumab) injection
[Ad hoc announcement pursuant to Art. 53 LR] Roche’s Tecentriq plus Avastin is the first treatment combination to reduce the risk of cancer returning in people with certain types of early-stage liver cancer in a Phase III trial January 19, 2023
- Pivotal Phase III IMbrave050 study investigating Tecentriq plus Avastin in people with early-stage hepatocellular carcinoma (HCC) at high risk of recurrence following surgery met primary endpoint of recurrence-free survival
- New adjuvant treatments are urgently needed as an estimated 70-80% of people with early-stage HCC experience disease recurrence following surgery1
- Data will be discussed with health authorities globally, including the US Food and Drug Administration and the European Medicines Agency to inform the next regulatory steps, and presented at an upcoming medical meeting
Basel, 19 January 2023 - Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced that the Phase III IMbrave050 study met its primary endpoint of recurrence-free survival (RFS) at the prespecified interim analysis. The study is evaluating Tecentriq® (atezolizumab) in combination with Avastin® (bevacizumab) as adjuvant treatment following surgery for people with early-stage hepatocellular carcinoma (HCC) at high risk of disease recurrence. The Tecentriq combination showed a statistically significant improvement in RFS in the intention-to-treat population of HCC patients who have an increased risk of recurrence following resection or ablation with curative intent, compared with active surveillance.
Overall survival data were immature at the time of interim analysis and follow-up will continue to the next analysis. Safety for Tecentriq and Avastin was consistent with the known safety profile of each therapeutic agent and with the underlying disease. Results from the IMbrave050 study will be discussed with health authorities, including the US Food and Drug Administration and the European Medicines Agency, and presented at an upcoming medical meeting.
“Today, more than 70% of people with early-stage HCC may have their cancer return after surgery, which is associated with poorer prognosis and shorter survival. IMbrave050 is the first Phase III study to show that a cancer immunotherapy combination reduced the risk of disease returning in people with this type of HCC,” said Levi Garraway, M.D., Ph.D., Chief Medical Officer and Head of Global Product Development. “We are excited by the clinical benefit that this adjuvant Tecentriq combination may bring to people with early liver cancer and look forward to seeing more mature data to further confirm the benefit.”
With liver cancer incidence increasing and mortality rates rising globally, effective treatments are urgently required.1-4 Roche is working in partnership with the community and leveraging its diagnostic and pharmaceutical expertise to develop solutions for patients that address unmet needs at each stage of liver cancer. IMbrave050 is part of Roche’s overall commitment to drive fundamental treatment change and improve outcomes for people living with liver cancer. In unresectable HCC (uHCC), for example, Tecentriq plus Avastin was the first treatment in over a decade to significantly improve overall survival over the existing standard of care, based on data from the IMbrave150 study. The Tecentriq combination quickly became a standard of care in uHCC and is clearly defined as a preferred front-line treatment in multiple international clinical guidelines.
Roche has an extensive development programme for Tecentriq, including multiple ongoing and planned Phase III studies across different lung, genitourinary, skin, breast, gastrointestinal, gynaecological, and head and neck cancers. This includes studies evaluating Tecentriq both alone and in combination with other medicines, as well as studies in metastatic, adjuvant and neoadjuvant settings across various tumour types.
About the IMbrave050 study
IMbrave050 is a Phase III global, multicentre, open-label, randomised study evaluating the efficacy and safety of adjuvant Tecentriq plus Avastin, compared with active surveillance, in people with HCC at high risk of recurrence (determined by the size and number of cancerous lesions and the histopathology results, if available) after surgical resection or ablation with curative intent.
The study randomised 662 people with a ratio of 1:1 to receive either Tecentriq (1,200 mg every three weeks) plus Avastin (15 mg/kg every three weeks) for a maximum of 12 months, or no intervention with active surveillance. The primary endpoint is independent review facility-assessed RFS. Key secondary endpoints include overall survival, RFS as determined by the investigator and RFS in patients with PD-L1-positive disease.
About Tecentriq
Tecentriq is a cancer immunotherapy approved for some of the most aggressive and difficult-to-treat forms of cancer. Tecentriq was the first cancer immunotherapy approved for the treatment of a certain type of early-stage non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC) and HCC. Tecentriq is also approved in countries around the world, either alone or in combination with targeted therapies and/or chemotherapies, for various forms of metastatic NSCLC, certain types of metastatic urothelial cancer, PD-L1-positive metastatic triple-negative breast cancer and BRAF V600 mutation-positive advanced melanoma.
Tecentriq is a monoclonal antibody designed to bind with a protein called programmed death ligand-1 (PD-L1), which is expressed on tumour cells and tumour-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the activation of T-cells. Tecentriq is a cancer immunotherapy that has the potential to be used as a foundational combination partner with other immunotherapies, targeted medicines and various chemotherapies across a broad range of cancers. In addition to intravenous infusion, the formulation of Tecentriq is also being investigated as a subcutaneous injection to help address the growing burden of cancer treatment for patients and healthcare systems.
https://www.avastin.com/hcp.html
https://www.avastin.com/patient/mcrc.html
About Roche
Founded in 1896 in Basel, Switzerland, as one of the first industrial manufacturers of branded medicines, Roche has grown into the world’s largest biotechnology company and the global leader in in-vitro diagnostics. The company pursues scientific excellence to discover and develop medicines and diagnostics for improving and saving the lives of people around the world. We are a pioneer in personalised healthcare and want to further transform how healthcare is delivered to have an even greater impact. To provide the best care for each person we partner with many stakeholders and combine our strengths in Diagnostics and Pharma with data insights from the clinical practice.
In recognising our endeavor to pursue a long-term perspective in all we do, Roche has been named one of the most sustainable companies in the pharmaceuticals industry by the Dow Jones Sustainability Indices for the thirteenth consecutive year. This distinction also reflects our efforts to improve access to healthcare together with local partners in every country we work.
Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan.
For more information, please visit www.roche.com.
All trademarks used or mentioned in this release are protected by law.
Roche's Tecentriq, Avastin combo cuts risk of liver cancer returning, in phase 3 trial
Jan. 19, 2023 4:55 AM ET
Roche Holding AG (RHHBY), RHHBF
By: Ravikash, SA News Editor
Roche (OTCQX:RHHBY) (OTCQX:RHHBF) said Tecentriq in combination with Avastin met the main goal of recurrence-free survival (RFS) in a phase 3 trial in patients with a type of liver cancer.
Roche Holding AG (RHHBY), RHHBF
Trodelvy® (sacituzumab govitecan-hziy)
TECENTRIQ® (atezolizumab) injection plus AVASTIN® (bevacizumab) injection
TECENTRIQ® (atezolizumab) injection plus AVASTIN® (bevacizumab) injection
January 03, 2023
European Medicines Agency Validates Marketing Authorization Application For Trodelvy® (sacituzumab govitecan-hziy) For Pre-treated HR+/HER2- Metastatic Breast Cancer
– Application Based on Statistically Significant and Clinically Meaningful Overall Survival and Progression-Free Survival Results from the Phase 3 TROPiCS-02 Study –
– Supplemental Biologics License Application Already Under Priority Review by the U.S. FDA –
FOSTER CITY, Calif.--(BUSINESS WIRE)-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced that the European Medicines Agency (EMA) has validated a Type II variation Marketing Authorization Application (MAA) for Trodelvy® (sacituzumab govitecan-hziy) for the treatment of adult patients with unresectable or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative (IHC 0, IHC 1+ or IHC 2+/ISH–) breast cancer who have received endocrine-based therapy and at least two additional systemic therapies in the metastatic setting.
“At Gilead Oncology our ambition is to transform care for people with cancer,” said Bill Grossman, MD, PhD, Senior Vice President, Therapeutic Area Head, Gilead Oncology. “Trodelvy is already moving us towards this ambition and changing the standard of care in second-line metastatic triple-negative breast cancer across the EU. The validation of our Marketing Authorization Application in pre-treated HR+/HER2- metastatic breast cancer marks an important step forward to potentially making Trodelvy available to even more patients with severely limited treatment options.”
This Marketing Authorization Application is based on data from the registrational Phase 3 TROPiCS-02 study, which met its primary endpoint of progression-free survival (PFS) and key secondary endpoint of overall survival (OS) versus comparator chemotherapies (treatment of physician’s choice (TPC) of chemotherapy). PFS data were published in the Journal of Clinical Oncology,and OS data were recently presented at ESMO Congress 2022.
The safety profile for Trodelvy in TROPiCS-02 was consistent with prior studies, and no new safety signals were identified in this population.
In October 2022, the U.S. Food and Drug Administration (FDA) accepted for priority review the supplemental Biologics License Application (sBLA) for Trodelvy for the treatment of adult patients with unresectable locally advanced or metastatic HR+/HER2-negative (IHC 0, IHC 1+ or IHC 2+/ISH–) breast cancer who have received endocrine-based therapy and at least two additional systemic therapies in the metastatic setting. The Prescription Drug User Fee Act (PDUFA) target action date is currently set for February 2023.
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
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 40 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 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/bladder-cancer
- Please see full Prescribing Information , including BOXED WARNING.
View source version on businesswire.com: https://www.businesswire.com/news/home/20230102005076/en/
Source: Gilead Sciences, Inc.
EMA approves change to marketing authorization for Gilead's breast cancer drug Trodelvy
Jan. 03, 2023 10:38 AM ET
By: Anuron Mitra, SA News Editor
Gilead Sciences (NASDAQ:GILD) on Tuesday said Europe's drug regulator had approved a change to its marketing authorization application for breast cancer treatment Trodelvy.
Calquence (acalabrutinib)
TECENTRIQ® (atezolizumab) injection plus AVASTIN® (bevacizumab) injection
Imfinzi (durvalumab) and Imjudo (tremelimumab)
Calquence approved in Japan for adults with treatment-naïve chronic lymphocytic leukaemia
PUBLISHED28 December 2022
28 December 2022 07:05 GMT
Calquence significantly increased the time patients lived without disease progression or death vs. chemoimmunotherapy
AstraZeneca’s Calquence (acalabrutinib), a selective Bruton’s tyrosine kinase (BTK) inhibitor, has been approved in Japan for the treatment of adult patients with treatment-naïve chronic lymphocytic leukaemia (CLL) (including small lymphocytic lymphoma [SLL]). Calquence was previously approved in Japan for the treatment of adults with relapsed or refractory CLL.
The approval by the Japanese Ministry of Health, Labour and Welfare (MHLW) was based on positive results from two clinical trials, including the ELEVATE-TN Phase III trial in adults with treatment-naïve CLL. This trial showed that Calquence combined with obinutuzumab or as monotherapy demonstrated a significantly improved progression-free survival (PFS) when compared with the chemotherapy-based combination of chlorambucil and obinutuzumab.1,2 Data from the interim analysis of ELEVATE-TN was published in The Lancet in 2020.2 Additionally, a Phase I trial in treatment-naïve Japanese patients with CLL was also submitted to MHLW supporting the approval, with the trial showing an overall response rate of 88.9% (95% CI: 63.2, 98.8%) for Calquence alone and 100% (95% CI: 66.4, 100%) for Calquence combined with obinutuzumab.
CLL is the most prevalent type of adult leukaemia across the globe but is considered a rare disease in Japan and East Asia, with fewer than one person newly diagnosed per 100,000 persons per year across Japan.3-5
Koji Izutsu, MD, PhD, Department Head, Department of Hematology, National Cancer Center Hospital, Tokyo, Japan, said: “Results from ELEVATE-TN and our local Japanese trial confirm that Calquence provides a significant improvement in progression-free survival compared with chemotherapy-based combination of chlorambucil and obinutuzumab for patients with treatment-naïve chronic lymphocytic leukaemia. Today’s approval marks great progress for physicians and patients in Japan, as they can now be treated with Calquence earlier in their treatment journey.”
Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: “The approval of Calquence in Japan for those with treatment-naïve chronic lymphocytic leukaemia now offers more patients a next-generation Bruton’s tyrosine kinase inhibitor that has proven longer-term efficacy and tolerability compared to standards of care. With this approval, people living with chronic lymphocytic leukaemia in Japan can now potentially benefit from our medicine in an earlier setting.”
Updated results of the ELEVATE-TN Phase III trial after a median follow-up of approximately five years were presented earlier this year. These results showed that Calquence maintained a statistically significant PFS benefit versus chlorambucil plus obinutuzumab, and a safety and tolerability profile consistent with the known profile for Calquence. At a median follow-up of 58.2 months, Calquence plus obinutuzumab reduced the risk of disease progression or death by 89% (based on a hazard ratio [HR] of 0.11, 95% confidence interval [CI] 0.07-0.16) and as a monotherapy by 79% (based on a HR of 0.21, 95% CI 0.15-0.30), compared with chlorambucil plus obinutuzumab.1
Calquence is approved for the treatment of CLL and SLL in the US and is approved for the treatment of CLL in the EU and in several other countries worldwide in the treatment-naïve and relapsed or refractory settings. Calquence is also approved in the US and several other countries for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. Calquence is not currently approved for the treatment of MCL in Japan or the EU.
Notes
CLL
CLL is the most prevalent type of leukaemia in adults, with over 100,000 new cases globally in 2019, but is considered a rare disease in Japan and East Asia, with fewer than one person newly diagnosed per 100,000 persons per year across Japan.3-5 Although some people with CLL may not experience any symptoms at diagnosis, others may experience symptoms, such as weakness, fatigue, weight loss, chills, fever, night sweats, swollen lymph nodes and abdominal pain.6
In CLL, there is an accumulation of abnormal lymphocytes within the bone marrow. As the number of abnormal cells increases, there is less room within the marrow for the production of normal white blood cells, red blood cells and platelets.7 This could result in anaemia, infection and bleeding. B-cell receptor signalling through BTK is one of the essential growth pathways for CLL.
ELEVATE-TN
ELEVATE-TN (ACE-CL-007) is a randomised, multicentre, open-label Phase III trial evaluating the safety and efficacy of Calquence alone or in combination with obinutuzumab versus chlorambucil in combination with obinutuzumab in previously untreated patients with CLL. In the trial, 535 patients were randomised (1:1:1) into three arms. Patients in the first arm received chlorambucil in combination with obinutuzumab. Patients in the second arm received Calquence (100mg twice daily until disease progression) in combination with obinutuzumab. Patients in the third arm received Calquence monotherapy (100mg twice daily until disease progression).8
The primary endpoint was PFS in the Calquence and obinutuzumab arm compared to the chlorambucil and obinutuzumab arm, assessed by an independent review committee (IRC), and a key secondary endpoint was IRC-assessed PFS in the Calquence monotherapy arm compared to the chlorambucil and obinutuzumab arm. Other secondary endpoints included overall response rate, time to next treatment, overall survival and investigator assessed PFS. After interim analysis, assessments were by investigator only.8
Initial results from the ELEVATE-TN Phase III trial were presented in December 2019 at the American Society of Hematology Annual Meeting and Exhibition. The trial met its primary endpoint (IRC-assessed PFS with Calquence plus obinutuzumab versus chlorambucil plus obinutuzumab) at the data cut-off for the interim analysis after a median follow-up of 28.3 months. The findings, along with previously reported data from the ASCEND Phase III trial in relapsed or refractory CLL, supported the approvals of Calquence by the US FDA and the Australian Therapeutic Goods Administration for the treatment of adult patients with CLL or SLL and by the European Medicines Agency (EMA) and Health Canada for CLL.
Calquence
Calquence (acalabrutinib) is a next-generation, selective inhibitor of BTK. Calquence binds covalently to BTK, thereby inhibiting its activity.9 In B cells, BTK signalling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis and adhesion.
Calquence is approved for the treatment of CLL and SLL in the US, approved for CLL in the EU and many other countries worldwide and approved in Japan for relapsed or refractory CLL and SLL.
In the US and several other countries, Calquence is 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, marginal zone lymphoma and other haematologic malignancies.
https://www.calquencehcp.com/mcl.html
AstraZeneca in haematology
AstraZeneca is pushing the boundaries of science to redefine care in haematology. We have expanded our commitment to patients with haematologic conditions, not only in oncology but also in rare diseases with the acquisition of Alexion, allowing us to reach more patients with high unmet needs. By applying our deep understanding of blood cancers, leveraging our strength in solid tumour oncology and delivering on Alexion’s pioneering legacy in complement science to provide innovative medicines for rare diseases, we are pursuing the end-to-end development of novel therapies designed to target underlying drivers of disease.
By targeting haematologic conditions with high unmet medical needs, we aim to deliver innovative medicines and approaches to improve patient outcomes. Our goal is to help transform the lives of patients living with malignant, rare and other related haematologic diseases, shaped by insights from patients, caregivers and physicians to have the most meaningful impact.
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.
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.
Japan approves AstraZeneca's blood cancer drug Calquence
Dec. 28, 2022 4:57 AM ET
By: Ravikash, SA News Editor
- The Japanese Ministry of Health, Labour and Welfare (MHLW) approved AstraZeneca's (NASDAQ:AZN) Calquence (acalabrutinib) to treat adult patients with treatment-naïve chronic lymphocytic leukemia (CLL), including small lymphocytic lymphoma (SLL).
- https://seekingalpha.com/news/3920862-japan-approves-astrazenecas-blood-cancer-drug-calquence
- AstraZeneca PLC (AZN)
- https://www.calquence.com/
- https://www.calquencehcp.com/mcl.html
Imfinzi (durvalumab) and Imjudo (tremelimumab)
Imfinzi (durvalumab) and Imjudo (tremelimumab)
Imfinzi (durvalumab) and Imjudo (tremelimumab)
Imfinzi plus Imjudo approved in Japan for advanced liver and non-small cell lung cancers, and Imfinzi approved for unresectable biliary tract and liver cancers
PUBLISHED28 December 2022 28 December 2022 07:00 GMT
Approvals based on significant survival benefits in
HIMALAYA, POSEIDON and TOPAZ-1 Phase III trials
AstraZeneca’s immunotherapies Imfinzi (durvalumab) and Imjudo (tremelimumab) have been approved in Japan for the treatment of three cancer types: advanced liver, biliary tract and lung.
The approvals authorise Imfinzi in combination with Imjudo for the treatment of adult patients with unresectable hepatocellular carcinoma (HCC) and for the treatment of adult patients with unresectable, advanced or recurrent non-small cell lung cancer (NSCLC) in combination with chemotherapy. Imfinzi was also authorised for the treatment of adult patients with unresectable HCC as monotherapy and for the treatment of adult patients with curatively unresectable biliary tract cancer (BTC) in combination with chemotherapy (gemcitabine plus cisplatin).
The concurrent approvals by the Japanese Ministry of Health, Labour, and Welfare are based on positive results from the HIMALAYA and TOPAZ-1 Phase III trials, each published in the New England Journal of Medicine Evidence and the POSEIDON Phase III trial, published in the Journal of Clinical Oncology.
Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: “Japan has one of the highest rates of diagnosis for liver and biliary tract cancers in the world, and lung cancer remains the country’s leading cause of cancer death. With these approvals for Imfinzi and Imjudo, patients in Japan can now be treated with novel immunotherapy-based treatment regimens that have demonstrated significant survival benefits across three complex cancers with poor prognoses.”
Imfinzi and Imjudo approved in liver cancer
The approval of Imfinzi in combination with Imjudo for the treatment of unresectable HCC brings the first dual immunotherapy treatment regimen to patients in Japan. The approval is based on results from the HIMALAYA Phase III trial, in which a single dose of the anti-CTLA-4 antibody Imjudo 300mg added to the anti-PD-L1 antibody Imfinzi 1500mg followed by Imfinzi every four weeks (STRIDE regimen: Single Tremelimumab Regular Interval Durvalumab) significantly reduced the risk of death versus sorafenib. The addition of Imjudo to Imfinzi did not increase severe liver toxicity, and no bleeding risk was observed.
HIMALAYA also served as the basis for the approval of Imfinzi monotherapy in the same disease setting. In HIMALAYA, Imfinzi demonstrated non-inferior overall survival (OS) compared to sorafenib, and an improved tolerability profile versus sorafenib.
The safety profiles of the combination of Imjudo added to Imfinzi and for Imfinzi alone were consistent with the known profiles of each medicine, and no new safety signals were identified.
Liver cancer is the fifth-leading cause of cancer death in Japan and the sixth most commonly diagnosed cancer worldwide.1,2 HCC is the most common type of liver cancer with 80% of cases occurring in the Asia-Pacific region.3,4 In Japan, approximately 45,000 people are diagnosed with HCC and 32,000 die of the disease each year.5,6
Imfinzi and Imjudo approved in NSCLC
The approval of Imfinzi and Imjudo plus chemotherapy for the treatment of unresectable, advanced or recurrent NSCLC is based on results from the POSEIDON Phase III trial, which showed a limited course of five cycles of the anti-CTLA-4 antibody Imjudo added to Imfinzi plus four cycles of platinum-based chemotherapy significantly reduced the risk of death versus a range of chemotherapy options.
The safety profile for Imjudo plus Imfinzi and chemotherapy was consistent with the known profiles of each medicine, and no new safety signals were identified.
In Japan, lung cancer is the most commonly diagnosed cancer, with more than 138,000 patients diagnosed in 2020.1 The prognosis for patients with metastatic NSCLC in Japan is particularly poor, as less than 20% will live beyond three years after diagnosis without treatment.7
Regulatory applications for Imfinzi and Imjudo are currently under review in the EU and several other countries based on the HIMALAYA, TOPAZ-1 and POSEIDON results.
Imfinzi plus chemotherapy approved in biliary tract cancer
The approval of Imfinzi plus chemotherapy brings the first immunotherapy regimen to patients with curatively unresectable BTC in Japan after more than a decade of limited innovation. The approval is based on results from an interim analysis of the TOPAZ-1 Phase III trial, which showed that Imfinzi plus chemotherapy significantly reduced the risk of death compared to chemotherapy alone. Imfinzi plus chemotherapy was generally well tolerated and did not increase the discontinuation rate due to adverse events compared to chemotherapy alone.
BTC is a group of rare and aggressive cancers that occur in the bile ducts and gallbladder.8,9 In 2021, approximately 23,300 people in Japan were diagnosed with BTC, which is the sixth-leading cause of cancer-related deaths for women and seventh-leading cause of cancer-related death for men in Japan.7 Patients face a poor prognosis, with approximately 19% to 31% of patients with BTC surviving five years.7
Notes
HIMALAYA
HIMALAYA was a randomised, open-label, multicentre, global Phase III trial of Imfinzi monotherapy and the STRIDE regimen comprising a single priming dose of Imjudo 300mg added to Imfinzi 1500mg followed by Imfinzi every four weeks versus sorafenib, a standard-of-care multi-kinase inhibitor.
The trial included a total of 1,324 patients with unresectable, advanced HCC who had not been treated with prior systemic therapy and were not eligible for locoregional therapy (treatment localised to the liver and surrounding tissue).
The trial was conducted in 181 centres across 16 countries, including in the US, Canada, Europe, South America and Asia. The primary endpoint was OS for the combination versus sorafenib and key secondary endpoints included OS for Imfinzi versus sorafenib, objective response rate (ORR) and progression-free survival (PFS) for the combination and for Imfinzi alone.
In HIMALAYA, the STRIDE regimen reduced the risk of death by 22% versus sorafenib (hazard ratio [HR] 0.78; 95% confidence interval [CI], 0.66-0.92; p= 0.0035). An estimated 31% of patients treated with the combination were still alive after three years, with 20% of patients treated with sorafenib still alive at the same duration of follow-up. The safety profiles of the combination of Imjudo added to Imfinzi and for Imfinzi alone were consistent with the known profiles of each medicine, and no new safety signals were identified.
POSEIDON
The POSEIDON trial was a randomised, open-label, multi-centre, global, Phase III trial of Imfinzi plus platinum-based chemotherapy, or Imfinzi, Imjudo 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 either Imfinzi (1,500mg) or Imfinzi plus Imjudo (75mg) with up to four cycles of chemotherapy every three weeks before either Imfinzi maintenance once every four weeks or Imfinzi and a fifth dose of Imjudo 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 Imjudo and chemotherapy arm. As both PFS endpoints were met for Imfinzi plus chemotherapy and Imfinzi, Imjudo and chemotherapy, the prespecified statistical analysis plan allowed for testing OS in the Imfinzi plus Imjudo 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.
Patients treated with a limited course of five cycles of the anti-CTLA-4 antibody Imjudo added to Imfinzi plus four cycles of platinum-based chemotherapy experienced a 23% reduction in the risk of death versus a range of chemotherapy options (HR 0.77; 95% CI, 0.65-0.92; p=0.00304). An estimated 33% of patients were alive at two years versus 22% for chemotherapy. This treatment combination also reduced the risk of disease progression or death by 28% compared to chemotherapy alone (HR 0.72; 95% CI, 0.60-0.86; p=0.00031).
Updated results after approximately four years of follow-up presented at the European Society for Medical Oncology Congress 2022 demonstrated sustained survival benefit, improving overall survival (OS) by 25% compared to chemotherapy alone (HR 0.75; 95% CI, 0.63-0.88). An estimated 25% of patients treated with the combination were alive at three years versus 13.6% for those treated with chemotherapy alone. The safety profile for Imjudo plus Imfinzi and chemotherapy was consistent with the known profiles of each medicine, and no new safety signals were identified.
TOPAZ-1
TOPAZ-1 was 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 was OS and key secondary endpoints included PFS, ORR 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.
At the interim analysis, Imfinzi plus chemotherapy reduced the risk of death by 20% versus chemotherapy alone (based on a hazard ratio [HR] of 0.80; 95% confidence interval [CI] 0.66-0.97; p=0.021). Updated results from TOPAZ-1 after an additional 6.5 months of follow-up showed a 24% reduction in the risk of death versus chemotherapy alone (HR 0.76; 95% CI, 0.64-0.91), with more than two times as many patients treated with Imfinzi plus chemotherapy estimated to be alive at two years versus chemotherapy alone (23.6% versus 11.5%). Updated median overall survival (OS) was 12.9 months versus 11.3 with chemotherapy. Imfinzi plus chemotherapy was generally well tolerated, with no new safety signals observed, and did not increase the discontinuation rate due to adverse events (AEs) compared to chemotherapy alone.
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 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 in combination with Imjudo and chemotherapy in metastatic non-small cell lung cancer in the US and Japan; in combination with chemotherapy in locally advanced or metastatic BTC in the US, Japan and several other countries; in combination with Imjudo in unresectable HCC in the US and Japan; as monotherapy in unresectable HCC in Japan; and in 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 gastrointestinal (GI) cancers, ovarian cancer, endometrial cancer and other solid tumours.
Imjudo
Imjudo (tremelimumab) is a human monoclonal antibody that targets the activity of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). Imjudo blocks the activity of CTLA-4, contributing to T-cell activation, priming the immune response to cancer and fostering cancer cell death.
In addition to its approved indications in liver and lung cancers, Imjudo is being tested in combination with Imfinzi across multiple tumour types including locoregional HCC (EMERALD-3), SCLC (ADRIATIC) and bladder cancer (VOLGA and NILE).
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.10
Within this programme, the Company is committed to improving outcomes in gastric, liver, BTC, oesophageal, pancreatic, and colorectal cancers.
Imfinzi is approved in the US and several other countries in combination with chemotherapy (gemcitabine plus cisplatin) for advanced biliary tract cancer and in the US and Japan in combination with Imjudo in unresectable HCC. Imfinzi is also approved as a monotherapy in unresectable HCC in Japan. Imfinzi is being assessed in combinations, including with Imjudo, in liver, oesophageal and gastric cancers in an extensive development programme spanning early to late-stage disease across settings.
Enhertu (trastuzumab deruxtecan), a HER2-directed antibody drug conjugate, is approved in the US and several other countries for HER2-positive advanced gastric cancer and is being assessed in colorectal cancer. Enhertu is jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.
Lynparza (olaparib), a first-in-class PARP inhibitor, is approved in the US and several other countries for the treatment of BRCA-mutated metastatic pancreatic cancer. Lynparza is developed and commercialised in collaboration with MSD (Merck & Co., Inc. inside the US and Canada).
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 and Imjudo; Enhertu 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 in immuno-oncology (IO)
AstraZeneca is a pioneer in introducing the concept of immunotherapy into dedicated clinical areas of high unmet medical need. The Company has a comprehensive and diverse IO portfolio and pipeline anchored in immunotherapies designed to overcome evasion of the anti-tumour immune response and stimulate the body’s immune system to attack tumours.
AstraZeneca aims to reimagine cancer care and help transform outcomes for patients with Imfinzi as a single treatment and in combination with Imjudo as well as other novel immunotherapies and modalities. The Company is also exploring next-generation immunotherapies like bispecific antibodies and therapeutics that harness different aspects of immunity to target cancer.
AstraZeneca is boldly pursuing an innovative clinical strategy to bring IO-based therapies that deliver long-term survival to new settings across a wide range of cancer types. With an extensive clinical programme, the Company also champions the use of IO treatment in earlier disease stages, where there is the greatest potential for cure.
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.
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's Imjudo/Imfinzi combo gets approval in Japan for liver, lung cancers
Dec. 28, 2022 4:40 AM ET
AstraZeneca PLC (AZN) By: Ravikash, SA News Editor
Japan's Ministry of Health, Labour, and Welfare approved AstraZeneca's (NASDAQ:AZN) immunotherapies Imfinzi and Imjudo to treat certain types of liver and lung cancers and Imfinzi to treat biliary tract and liver cancers.
LIBTAYO® (CEMIPLIMAB)
Imfinzi (durvalumab) and Imjudo (tremelimumab)
YESCARTA® (axicabtagene ciloleucel)
December 23, 2022 at 8:30 AM EST
LIBTAYO® (CEMIPLIMAB) APPROVED IN JAPAN FOR ADVANCED OR RECURRENT CERVICAL CANCER
TARRYTOWN, N.Y., Dec. 23, 2022 /PRNewswire/ -- Regeneron Pharmaceuticals (NASDAQ: REGN) today announced that the Ministry of Health, Labor and Welfare (MHLW) in Japan has granted marketing and manufacturing authorization for Libtayo® (cemiplimab) as monotherapy to treat patients with advanced or recurrent cervical cancer whose disease progressed after chemotherapy.
"In recent years, the incidence of cervical cancer has increased in Japan, with the prognosis for advanced stage disease remaining poor and treatment options limited," said Israel Lowy, M.D., Ph.D., Senior Vice President, Translational and Clinical Sciences, Oncology at Regeneron. "With this approval, Libtayo becomes the first single-agent immunotherapy approved in Japan for the treatment of advanced cervical cancer."
The MHLW approval is based on positive data from the international, multicenter Phase 3 EMPOWER-Cervical 1 trial, conducted in collaboration with NRG Oncology-Japan, the GOG Foundation, Inc., and the European Network for Gynaecological Oncological Trial (ENGOT) groups. The trial evaluated Libtayo compared to an investigator's choice of chemotherapy and enrolled 608 patients across 14 countries, including Japan, irrespective of PD-L1 expression status or histology. In March 2021, the trial was stopped early based on the highly significant effect of Libtayo on overall survival among squamous cell carcinoma patients following a unanimous recommendation by the Independent Data Monitoring Committee.
"With Libtayo, Japan now has an approved treatment option that has demonstrated significant survival benefits in this cervical cancer patient population compared to chemotherapy irrespective of PD-L1 expression – a milestone no other PD-1 inhibitor has achieved in a Phase 3 trial," said Prof. Kosei Hasegawa, Gynecologic Oncology, Saitama Medical University International medical Center, a trial investigator and a member of NRG Oncology-Japan. "We are proud to have contributed to bringing this new treatment option to women living with this difficult-to-treat cancer in Japan.
Cervical cancer is the fourth leading cause of cancer death in women worldwide and is most frequently diagnosed in women between the ages of 35 and 44. Almost all cases of cervical cancer are caused by human papillomavirus (HPV) infection. It is estimated that approximately 600,000 new cases of cervical cancer are diagnosed and 350,000 deaths from cervical cancer occur worldwide each year.
In November 2022, Libtayo was approved by the European Commission for the treatment of adult patients with recurrent or metastatic cervical cancer and disease progression on or after platinum-based chemotherapy.
About Libtayo
Libtayo is a fully human monoclonal antibody targeting the immune checkpoint receptor PD-1 on T cells and was invented using Regeneron's proprietary VelocImmune® technology. By binding to PD-1, Libtayo has been shown to block cancer cells from using the PD-1 pathway to suppress T-cell activation. In the U.S. and other countries Libtayo is indicated in certain patients with advanced basal cell carcinoma (BCC), advanced CSCC and advanced non-small cell lung cancer (NSCLC), as well as in advanced cervical cancer in Japan, the European Union, Canada and Brazil.
Libtayo was jointly developed by Sanofi and Regeneron under a global collaboration agreement. As of July 1, 2022, Regeneron is responsible for the development and marketing of Libtayo globally. In Japan, Libtayo is currently marketed by Sanofi on Regeneron's behalf over the course of a defined transition period.
The extensive clinical program for Libtayo is focused on difficult-to-treat cancers. Libtayo is currently being investigated in trials as a monotherapy, as well as in combination with either conventional or novel therapeutic approaches for other solid tumors and blood cancers. These potential uses are investigational, and their safety and efficacy have not been evaluated by any regulatory authority.
U.S. FDA-approved Indications
Libtayo is a prescription medicine used to treat:
-- People with a type of skin cancer called CSCC that has spread or cannot be cured by surgery or radiation.
-- People with a type of skin cancer called BCC:
- That cannot be removed by surgery (locally advanced BCC) and have received treatment with a hedgehog pathway inhibitor (HHI), or cannot receive treatment with an HHI.
- That has spread (metastatic BCC) and have received treatment with an HHI, or cannot receive treatment with an HHI. This use is approved based on how many patients responded to treatment and how long they responded. Studies are ongoing to provide additional information about clinical benefit.
-- Adults with a type of lung cancer called NSCLC:
- Libtayo may be used in combination with chemotherapy that contains a platinum medicine as your first treatment when your lung cancer has not spread outside your chest (locally advanced lung cancer) and you cannot have surgery or chemotherapy with radiation, OR your lung cancer has spread to other areas of your body (metastatic lung cancer), AND your tumor does not have an abnormal "EGFR", "ALK" or "ROS1" gene.
- Libtayo may be used alone as your first treatment when your lung cancer has not spread outside your chest (locally advanced lung cancer) and you cannot have surgery or chemotherapy with radiation, OR your lung cancer has spread to other areas of your body (metastatic lung cancer), AND your tumor tests positive for high "PD-L1", AND your tumor does not have an abnormal "EGFR", "ALK "or "ROS1" gene.
It is not known if Libtayo is safe and effective in children.
Please see full Prescribing Information, including Medication Guide.
About Regeneron in Oncology
At Regeneron, we're applying more than three decades of scientific innovation with the goal of developing paradigm-changing therapies for patients with cancer. Our oncology portfolio is built around two foundational approaches – our approved PD-1 inhibitor Libtayo and investigational bispecific antibodies – which are being evaluated both as monotherapies and in combination with emerging therapeutic modalities. Together, they provide us with unique combinatorial flexibility to develop potentially synergistic treatments for a wide range of solid tumors and blood cancers.
If you are interested in learning more about our clinical trials, please contact us (clinicaltrials@regeneron.com or 844-734-6643) or visit our clinical trials website.
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® (dupilumab), Libtayo, Praluent® (alirocumab), Kevzara® (sarilumab), Evkeeza® (evinacumab-dgnb) and Inmazeb™ (atoltivimab, maftivimab and odesivimab-ebgn).
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.
View original content:https://www.prnewswire.com/news-releases/libtayo-cemiplimab-approved-in-japan-for-advanced-or-recurrent-cervical-cancer-301709636.html
SOURCE Regeneron Pharmaceuticals, Inc.
Regeneron's Libtayo approved in Japan for cervical cancer
Dec. 23, 2022 9:01 AM ET
Regeneron Pharmaceuticals, Inc. (REGN)
By: Jonathan Block, SA News Editor
- Japanese regulators have granted marketing authorization to Regeneron's (NASDAQ:REGN) Libtayo (cemiplimab) for advanced or recurrent cervical cancer.
- https://seekingalpha.com/news/3920272-regeneron-libtayo-approved-in-japan-for-cervical-cancer
- Regeneron Pharmaceuticals, Inc. (REGN)
- https://www.libtayo.com/
- https://www.regeneron.com/
YESCARTA® (axicabtagene ciloleucel)
Imfinzi (durvalumab) and Imjudo (tremelimumab)
YESCARTA® (axicabtagene ciloleucel)
December 22, 2022
Yescarta® Now Approved in Japan for Initial Treatment of Relapsed/Refractory Large B-Cell Lymphoma
– Based on Landmark ZUMA-7 Study, Patients with LBCL Treated with Yescarta in Second-Line Achieved Four-Fold Greater Improvement in Event-Free Survival of 8.3 Months vs. Two Months for Standard of Care (SOC)
– In ZUMA-7, Patients Treated with Yescarta Were 2.5 Times More Likely than SOC to be Alive at Two Years Without Disease Progression or Need for Additional Treatments –
SANTA MONICA, Calif. & TOKYO--(BUSINESS WIRE)-- Kite Pharma, Inc., a Gilead Company, (hereafter, Kite) (NASDAQ: GILD) and Daiichi Sankyo Co., Ltd. (hereafter, Daiichi Sankyo) (TSE: 4568) today jointly announced that the Japan Ministry of Health, Labour and Welfare (MHLW) has approved Yescarta (axicabtagene ciloleucel), a chimeric antigen receptor (CAR) T-cell therapy, for the initial treatment of patients with relapsed/refractory large B-cell lymphoma ( R/R LBCL): diffuse large B-cell lymphoma, primary mediastinal large B-cell lymphoma, transformed follicular lymphoma, and high-grade B-cell lymphoma. Yescarta should be used only in patients who have not received prior transfusion of CAR T-cells targeted at CD19 antigen.
This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20221222005384/en/
The Standard of Care (SOC) to treat LBCL patients has historically been a multi-step process that starts with chemoimmunotherapy, followed by high-dose chemotherapy (HDT) and then ends with a stem cell transplant (ASCT). Although approximately 60% of newly diagnosed LBCL patients will respond to the initial treatment with chemotherapy, 40% will relapse or will not respond and need second-line treatment. Yescarta is now approved for the initial treatment of R/R LBCL patients in Japan.
“We are very proud of this additional Yescarta approval in Japan,” said Christi Shaw, CEO of Kite. “As Japan has the second-largest number of people diagnosed with non-Hodgkin lymphoma globally, this approval marks an important step in bringing this innovative therapy earlier to more patients.”
“We are glad to have achieved this important milestone in order to provide an innovative treatment option to more patients with large B-cell lymphoma in Japan,” said Wataru Takasaki, PhD, Executive Officer, Head of R&D Division in Japan, Daiichi Sankyo. “It also further demonstrates the expertise of our Daiichi Sankyo R&D organization as we had successfully expanded the indication for this CAR-T modality.”
The approval of Yescarta for the initial treatment of R/R LBCL patients in Japan is based on clinical data, including the results of the global pivotal trial conducted by Kite (ZUMA-7). ZUMA-7 is the largest and longest trial of a CAR T-cell therapy versus SOC in this patient population. Results from the study 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<0.0001) over the current SOC (8.3 months vs 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%).
This indication was first approved by the U.S. FDA in April 2022 followed by the European Commission in October 2022.
On December 7, 2022, Daiichi Sankyo and Kite jointly announced that the Marketing Authorization for Yescarta will be transferred to Gilead Sciences K.K., the Japan subsidiary of Gilead Sciences, Inc., in 2023. The Kite Cell Therapy Business Unit at Gilead Sciences K.K. will manage the sales and promotion activities of the product in Japan after the Marketing Authorization transfer.
Kite’s manufacturing facility in El Segundo, California, U.S., has been approved by Japanese regulatory authorities to commence manufacturing Yescarta for the Japan market in 2023.
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). Key secondary endpoints include objective response rate (ORR) and overall survival (OS). Additional secondary endpoints include patient reported outcomes and safety.
About YESCARTA®
Yescarta (axicabtagene ciloleucel) is a CAR T-cell therapy directed against CD19 (a cell membrane protein), which harnesses a patient’s own immune system to fight cancer. Axicabtagene ciloleucel is made by removing a patient’s T cells from their blood and engineering them in the lab to express chimeric antigen receptors so that they can recognize and destroy cancer cells when they are infused back to the patient’s body. The CAR T-cell therapy is manufactured specifically for each patient and administered only once. Axicabtagene ciloleucel received Orphan Drug Designation from the Japan MHLW in 2018 for the treatment of diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, transformed follicular lymphoma and high-grade B-cell lymphoma. Yescarta was approved in Japan for the treatment of patients with relapsed or refractory large B-cell lymphomas, a type of non-Hodgkin lymphoma, in January 2021.
https://www.yescarta.com/lbcl/
Please see full U.S. 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. (1.1)
- 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. (1.1)
- 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 response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s). (1.2)
For the full European Prescribing Information, please visit: : https://www.ema.europa.eu/en/medicines/human/EPAR/yescarta.
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.
About Kite
Kite, a Gilead Company, is a global biopharmaceutical company based in Santa Monica, California, focused on cell therapy to treat and potentially cure cancer. As the global cell therapy leader, Kite has treated more patients with CAR T-cell therapy than any other company. Kite has the largest in-house cell therapy manufacturing network in the world, spanning process development, vector manufacturing, clinical trial production and commercial product manufacturing. For more information on Kite, please visit www.kitepharma.com.
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. Gilead Sciences acquired Kite in 2017.
U.S. Prescribing Information for Yescarta including BOXED WARNING, is available at www.kitepharma.com and www.gilead.com .
Kite, the Kite logo, Yescarta, and GILEAD are trademarks of Gilead Sciences, Inc. or its related companies.
View source version on businesswire.com: https://www.businesswire.com/news/home/20221222005384/en/
Source: Gilead Sciences, Inc.
Gilead's Yescarta approved in Japan for initial treatment of B-cell lymphomas
Dec. 22, 2022 4:59 PM ET
Gilead Sciences, Inc. (GILD), DSKYF, DSNKY
By: Anuron Mitra, SA News Editor
- Gilead Sciences' (NASDAQ:GILD) Kite Pharma and Japanese pharmaceutical giant Daiichi Sankyo (OTCPK:DSKYF) (OTCPK:DSNKY) on Thursday said that cancer drug Yescarta had received approval from the country's health ministry for initial treatment of various types of B-cell lymphoma.
- https://seekingalpha.com/news/3920108-gileads-yescarta-approved-in-japan-for-initial-treatment-of-b-cell-lymphomas
- Gilead Sciences, Inc. (GILD), DSKYF, DSNKY
- https://www.yescarta.com/lbcl/
- https://www.gilead.com/
BIOTECNOVA™
Imfinzi (durvalumab) plus chemotherapy
LYNPARZA® (olaparib) in Combination With Abiraterone and Prednisone or Prednisolone
LYNPARZA® (olaparib) in Combination With Abiraterone and Prednisone or Prednisolone
Imfinzi plus chemotherapy approved in the EU as first immunotherapy regimen for patients with advanced biliary tract cancer
PUBLISHED21 December 2022
21 December 2022 07:00 GMT
Approval based on TOPAZ-1 updated survival results showing Imfinzi
combination reduced risk of death by 24% vs. chemotherapy alone
AstraZeneca’s Imfinzi (durvalumab) has been approved in the European Union (EU) for the 1st-line treatment of adult patients with unresectable or metastatic biliary tract cancer (BTC) in combination with chemotherapy (gemcitabine plus cisplatin).
The approval by the European Commission was based on the primary results from the TOPAZ-1 Phase III trial published in the New England Journal of Medicine Evidence, and on the updated results presented at the European Society for Medical Oncology Congress 2022. The approval follows the recommendation by The Committee for Medicinal Products for Human Use of the European Medicines Agency in November 2022.
At the interim analysis, Imfinzi plus chemotherapy reduced the risk of death by 20% versus chemotherapy alone (based on a hazard ratio [HR] of 0.80; 95% confidence interval [CI] 0.66-0.97; p=0.021). Updated results from TOPAZ-1 after an additional 6.5 months of follow-up showed a 24% reduction in the risk of death versus chemotherapy alone (HR 0.76; 95% CI, 0.64-0.91), with more than two times as many patients treated with Imfinzi plus chemotherapy estimated to be alive at two years versus chemotherapy alone (23.6% versus 11.5%). Updated median overall survival (OS) was 12.9 months versus 11.3 with chemotherapy.
BTC is a group of rare and aggressive cancers that occur in the bile ducts (cholangiocarcinoma) and gallbladder.1,2 There are approximately 211,000 new patients diagnosed with gallbladder and biliary tract cancer each year, and about 40,000 of these occur across Europe.3 These patients have a poor prognosis, with approximately 5% to 15% of patients with BTC surviving five years.4
Juan W. Valle, MD, Professor of Medical Oncology at the University of Manchester and The Christie NHS Foundation Trust, UK, and a lead investigator in the TOPAZ-1 Phase III trial, said: “Today’s approval marks an important shift in the treatment of this aggressive and often overlooked disease and a significant improvement compared to standard of care for these patients. After waiting over a decade for new therapeutic options, biliary tract cancer patients in the EU will now have the opportunity to benefit from an immunotherapy-based treatment for the first time.”
Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: “With this approval, Imfinzi plus chemotherapy becomes the only immunotherapy-based treatment option available to patients in the EU with advanced biliary tract cancer. This approval underscores our commitment to transform survival outcomes while addressing the high unmet need for new and improved treatments for patients with hepatobiliary cancers.”
Imfinzi plus chemotherapy was generally well tolerated, with no new safety signals observed, and did not increase the discontinuation rate due to adverse events (AEs) compared to chemotherapy alone. Grade 3 or 4 treatment-related AEs were experienced by 60.9% of patients treated with Imfinzi plus chemotherapy, and by 63.5% of patients treated with chemotherapy alone.
Imfinzi plus chemotherapy is approved in the US and other countries for the treatment of adults with locally advanced or metastatic BTC. Regulatory applications are also currently under review in Japan and several other countries based on the TOPAZ-1 results.
Notes
Biliary tract cancer
BTC is a group of rare and aggressive gastrointestinal (GI) cancers that form in the cells of the bile ducts (cholangiocarcinoma), gallbladder or ampulla of Vater (where the bile duct and pancreatic duct connect to the small intestine).1,2
Early-stage BTC affecting the bile ducts and gallbladder often presents without clear symptoms and most new cases of BTC are therefore diagnosed at an advanced stage, when treatment options are limited and the prognosis is poor.4-6 Cholangiocarcinoma is more common in China and Southeast Asia and is on the rise in Western countries.1,4
TOPAZ-1
TOPAZ-1 was 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 was 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.
Imfinzi is the only approved immunotherapy in unresectable or metastatic BTC, unresectable hepatocellular carcinoma [in combination with Imjudo (tremelimumab)], and the curative-intent setting of unresectable, Stage III non-small cell lung cancer (NSCLC) in patients whose disease has not progressed after chemoradiotherapy. It 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 in the US for the treatment of adult patients with Stage IV (metastatic) NSCLC in combination with Imjudo and chemotherapy.
Imfinzi is also approved for previously treated patients with advanced bladder cancer in several countries.
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.7
Within this programme, the Company is committed to improving outcomes in gastric, liver, biliary tract, oesophageal, pancreatic, and colorectal cancers.
Imfinzi is approved in the US in combination with chemotherapy (gemcitabine plus cisplatin) for advanced BTC and in combination with Imjudo in unresectable hepatocellular carcinoma. Imfinzi is being assessed in combinations, including with Imjudo in liver, oesophageal and gastric cancers in an extensive development programme spanning early to late-stage disease across settings.
Enhertu (trastuzumab deruxtecan), a HER2-directed antibody drug conjugate, is approved in HER2-positive advanced gastric cancer and is being assessed in colorectal cancer. Enhertu is jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.
Lynparza (olaparib), a first-in-class PARP inhibitor, is approved in BRCA-mutated metastatic pancreatic cancer. Lynparza is developed and commercialised in collaboration with MSD (Merck & Co., Inc. inside the US and Canada).
AstraZeneca in immuno-oncology (IO)
AstraZeneca is a pioneer in introducing the concept of immunotherapy into dedicated clinical areas of high unmet medical need. The Company has a comprehensive and diverse IO portfolio and pipeline anchored in immunotherapies designed to overcome evasion of the anti-tumour immune response and stimulate the body’s immune system to attack tumours.
AstraZeneca aims to reimagine cancer care and help transform outcomes for patients with Imfinzi as a single treatment and in combination with Imjudo as well as other novel immunotherapies and modalities. The Company is also exploring next-generation immunotherapies like bispecific antibodies and therapeutics that harness different aspects of immunity to target cancer.
AstraZeneca is boldly pursuing an innovative clinical strategy to bring IO-based therapies that deliver long-term survival to new settings across a wide range of cancer types. With an extensive clinical programme, the Company also champions the use of IO treatment in earlier disease stages, where there is the greatest potential for cure.
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.
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 Imfinzi combo for biliary tract cancer gets approval in EU
Dec. 21, 2022 4:50 AM ET
By: Ravikash, SA News Editor
- The European Commission (EC) approved AstraZeneca's (NASDAQ:AZN) Imfinzi in combination with chemotherapies gemcitabine and cisplatin, as a first‑line treatment for adults with unresectable or metastatic biliary tract cancer (BTC).
- https://seekingalpha.com/news/3919300-astrazenecas-imfinzi-combo-for-biliary-tract-cancer-gets-approval-in-eu
- AstraZeneca PLC (AZN)
- https://www.astrazeneca.com/
- https://www.imfinzi.com/
LYNPARZA® (olaparib) in Combination With Abiraterone and Prednisone or Prednisolone
LYNPARZA® (olaparib) in Combination With Abiraterone and Prednisone or Prednisolone
LYNPARZA® (olaparib) in Combination With Abiraterone and Prednisone or Prednisolone
LYNPARZA® (olaparib) in Combination With Abiraterone and Prednisone or Prednisolone Approved in the EU as Treatment for Certain Patients With Metastatic Castration-Resistant Prostate Cancer
December 21, 2022 6:45 am ET
First PARP inhibitor and new hormonal agent combination approved for these patients in Europe
RAHWAY, N.J.--(BUSINESS WIRE)-- AstraZeneca and Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced that LYNPARZA has been approved in the European Union (EU) in combination with abiraterone and prednisone or prednisolone for the treatment of adult patients with metastatic castration-resistant prostate cancer (mCRPC) in whom chemotherapy is not clinically indicated.
This approval by the European Commission follows the positive recommendation from the Committee for Medicinal Products for Human Use received in November this year and was based on the Phase 3 PROpel trial, results of which were published in NEJM Evidence in June 2022.
In PROpel, LYNPARZA in combination with abiraterone and prednisone or prednisolone reduced the risk of disease progression or death by 34% (HR=0.66 [95% CI, 0.54-0.81]; p<0.0001) versus placebo plus abiraterone and prednisone or prednisolone, based on investigator assessment. Median radiographic progression-free survival (rPFS) was 24.8 months for the LYNPARZA plus abiraterone arm (95% CI, 20.5, 27.6) versus 16.6 months for the placebo plus abiraterone arm (95% CI, 13.9, 19.2). A planned sensitivity analysis by blinded independent central review was consistent with the investigator-based analysis, with a median rPFS of 27.6 months for the LYNPARZA plus abiraterone arm compared to 16.4 months for the placebo plus abiraterone arm.
Interim results for the key secondary efficacy endpoint of overall survival (OS) did not reach statistical significance, with an event rate of 37.1% in the LYNPARZA plus abiraterone arm versus 43.1% in the placebo plus abiraterone arm at the time of the analysis (HR=0.83 [95% CI, 0.66-1.03]).
The safety and tolerability of LYNPARZA in combination with abiraterone and prednisone or prednisolone was generally consistent with that of the individual medicines. Approximately 16% of patients who received LYNPARZA in combination with abiraterone and prednisone or prednisolone discontinued treatment due to an adverse event (AE). As previously reported, based on an analysis from the PROpel trial presented earlier this year at the American Society of Clinical Oncology Genitourinary Cancers Symposium, the most common AEs (≥20%) were anemia (46%), fatigue (37%) and nausea (28%). Grade ≥3 AEs were anemia (15%), hypertension (4%), urinary tract infection (2%), fatigue (2%), decreased appetite (1%), vomiting (1%), back pain (1%), diarrhea (1%) and nausea (0.3%).
Prostate cancer is the most commonly diagnosed cancer in men in Europe, with an estimated 473,000 cases and 108,000 deaths in 2020. Approximately 10-20% of patients with prostate cancer are estimated to develop castration-resistant prostate cancer (CRPC) within five years, with at least 84% of these patients presenting with metastases at the time of CRPC diagnosis. Patients diagnosed with advanced prostate cancer have a particularly poor prognosis, with a five-year relative survival rate of about 30%, compared to patients diagnosed with earlier stages of the disease, with a five-year relative survival rate of more than 99%.
Noel Clarke, urological surgeon and professor of urological oncology at Manchester’s Christie/Salford Royal Hospitals and Manchester University, a senior investigator of the PROpel trial, said, “The results of the PROpel Phase 3 trial of olaparib in combination with abiraterone as a first-line treatment show that this therapeutic combination can provide significant clinical benefit to patients with mCRPC. Patients with this condition in the EU will now, for the first time, have the opportunity to benefit from this new treatment combination.”
Dave Fredrickson, executive vice president, oncology business unit, AstraZeneca, said, “Many patients with mCRPC are only able to receive one line of active therapy, as the disease can progress quickly. LYNPARZA in combination with abiraterone has been shown to reduce the risk of disease progression by 34% versus the standard of care treatment in the PROpel trial. Moreover, the combination of LYNPARZA with abiraterone as a first-line treatment expands the use of LYNPARZA to a broader group of mCRPC patients than those treated with LYNPARZA alone in the second-line setting in the PROfound trial. Today’s approval marks a significant advance toward addressing the unmet need of patients with mCRPC in the EU.”
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 mCRPC, a complex disease that urgently needs more therapies. This approval by the European Commission marks another step toward delivering on that commitment, and we look forward to extending the benefits of LYNPARZA to more patients with mCRPC in the EU.”
Use of LYNPARZAin combination with abiraterone and prednisone or prednisolone is currently under review by the U.S. FDA for the treatment of adult patients with mCRPC. LYNPARZA is approved in the U.S. as monotherapy for patients with homologous recombination repair (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 (NHA). These approvals were based on the data from the Phase 3 PROfound trial.
About PROpel
PROpel is a randomized, double-blind Phase 3 trial testing the efficacy, safety and tolerability of LYNPARZA versus placebo when given in addition to abiraterone and prednisone or prednisolone in patients with mCRPC who had not received prior chemotherapy or NHAs in the mCRPC setting. The major efficacy outcome was rPFS as assessed by investigator per RECIST v1.1 and Prostate Cancer Working Group (bone) criteria. OS was an additional efficacy outcome measure.
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.
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 .
Financial considerations
Under the oncology collaboration with AstraZeneca and following this new approval for LYNPARZA, AstraZeneca will receive a $105 million payment from Merck.
About LYNPARZA® (olaparib)
LYNPARZAis a first-in-class PARP inhibitor and the first targeted treatment to potentially exploit DNA damage response (DDR) pathway deficiencies, such as BRCA mutations, to preferentially kill cancer cells. 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 tumor types with defects and dependencies in the DDR.
LYNPARZA, which is being jointly developed and commercialized by AstraZeneca and Merck, has a broad clinical trial development program, and AstraZeneca and Merck are working together to understand how it may affect multiple PARP-dependent tumors as a monotherapy and in combination across multiple cancer types.
About the AstraZeneca and Merck strategic oncology collaboration
In July 2017, AstraZeneca and Merck, known as MSD outside of the United States and Canada, announced a global strategic oncology collaboration to co-develop and co-commercialize certain oncology products including LYNPARZA, the world’s first PARP inhibitor, for multiple cancer types. Working together, the companies will develop these products in combination with other potential new medicines and as monotherapies. Independently, the companies will develop these oncology productsin combination with their respective PD-L1 and PD-1 medicines.
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.
Source: Merck & Co., Inc.
AstraZeneca, Merck's Lynparza gets approval in EU for expanded use in prostate cancer
Dec. 21, 2022 4:29 AM ET
By: Ravikash, SA News Editor
- The European Commission (EC) approved AstraZeneca (NASDAQ:AZN) and Merck's (NYSE:MRK) Lynparza in combination with abiraterone and prednisone or prednisolone, to treat adult men with metastatic castration-resistant prostate cancer for whom chemotherapy is not clinically indicated.
- https://seekingalpha.com/news/3919299-astrazeneca-mercks-lynparza-gets-approval-in-eu-for-expanded-use-in-prostate-cancer
- AstraZeneca PLC (AZN), MRK
- https://www.lynparza.com/
- https://www.merck.com/
- https://www.astrazeneca.com/
PADCEV® (enfortumab vedotin-ejfv) with KEYTRUDA® (pembrolizumab)
LYNPARZA® (olaparib) in Combination With Abiraterone and Prednisone or Prednisolone
PADCEV® (enfortumab vedotin-ejfv) with KEYTRUDA® (pembrolizumab)
Seagen, Astellas and Merck Announce FDA Acceptance of sBLAs for PADCEV® (enfortumab vedotin-ejfv) with KEYTRUDA® (pembrolizumab) for the First-Line Treatment of Certain Patients With Locally Advanced or Metastatic Urothelial Cancer
12/20/2022
– This combination has the potential to be the first treatment option combining an antibody-drug conjugate plus an immunotherapy in this treatment setting –
– FDA granted the applications Priority Review with a PDUFA date of April 21, 2023 –
BOTHELL, Wash. & TOKYO & RAHWAY, N.J.--(BUSINESS WIRE)--
Seagen Inc. (Nasdaq: SGEN),Astellas Pharma Inc. (TSE:4503) and Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced the U.S. Food and Drug Administration (FDA) has accepted for Priority Review supplemental Biologics License Applications (sBLAs) for PADCEV® (enfortumab vedotin-ejfv) and KEYTRUDA® (pembrolizumab) for use of these two agents in combination for the treatment of patients with locally advanced or metastatic urothelial cancer (la/mUC) who are not eligible to receive cisplatin-containing chemotherapy. The respective applications are intended to expand both labels for PADCEV and KEYTRUDA. The agency set a Prescription Drug User Fee Act (PDUFA) goal date for each application of April 21, 2023.
This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20221220005198/en/
“We look forward to working closely with the FDA as we seek potential accelerated approval for this combination in the hopes that it can be another treatment option for patients with locally advanced or metastatic urothelial cancer who are not eligible for cisplatin-containing chemotherapy,” said Ahsan Arozullah, M.D., M.P.H., Senior Vice President and Head of Development Therapeutic Areas, Astellas.
The combination therapy was granted Breakthrough Therapy designation by the FDA in February 2020. The respective sBLAs are supported by efficacy and safety data from the phase 1b/2 EV-103 trial (NCT03288545, also known as KEYNOTE-869) Dose Escalation/Cohort A and Cohort K. Results from Dose Escalation/Cohort A were published in the Journal of Clinical Oncology.1 Results from Cohort K were presented in a late-breaking session at the 2022 European Society for Medical Oncology (ESMO) Congress.2
“Urothelial cancer, the most common type of bladder cancer, is associated with poor survival in the advanced stage,” said Marjorie Green, M.D., Senior Vice President and Head of Late-Stage Development, Seagen. “The investigational results from our clinical development program support the combination of PADCEV and KEYTRUDA as a potential treatment for this patient population.”
Please see Important Safety Information at the end of this press release for both drugs, including a warning and precaution for immune-mediated adverse reactions for pembrolizumab and BOXED WARNING for PADCEV (enfortumab vedotin-ejfv) for serious skin reactions.
“Despite advancements in treatment options, approximately half of advanced bladder cancer patients in the U.S. are ineligible for cisplatin-based chemotherapy, and these patients need new options. We are encouraged by the investigational results of the combination of PADCEV and KEYTRUDA for this patient population and are fully committed to work to bring this new approach forward to patients,” said Dr. Eliav Barr, Senior Vice President, Head of Global Clinical Development and Chief Medical Officer, Merck Research Laboratories.
Seagen, Astellas and Merck are further investigating enfortumab vedotin plus pembrolizumab in the ongoing phase 3 EV-302 study (NCT04223856, also known as KEYNOTE-A39), evaluating the clinical benefit for the investigational treatment combination in patients with previously untreated advanced urothelial cancer. The trial is intended to serve as the confirmatory trial for the potential accelerated approval in the U.S. and serve as the basis for global registration.
The studies are part of an extensive program evaluating this combination in multiple stages of urothelial cancer, including two phase 3 clinical trials in muscle-invasive bladder cancer in EV-304 (NCT04700124, also known as KEYNOTE-B15) and EV-303 (NCT03924895, also known as KEYNOTE-905).
About the EV-103/KEYNOTE-869 Trial
The EV-103 trial (NCT03288545) is an ongoing, multi-cohort, open-label, multicenter phase 1b/2 study 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.
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.7 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).8
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.8
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.
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.
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.
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, NJ, USA.
View source version on businesswire.com: https://www.businesswire.com/news/home/20221220005198/en/
Source: Seagen Inc.
Merck, Seagen, Astellas combo bladder cancer treatment sBLAs accepted by FDA
Dec. 20, 2022 8:41 AM ET
Astellas Pharma Inc. (ALPMF), ALPMY, SGEN, MRK
By: Jonathan Block, SA News Editor
- The US FDA has accepted supplemental Biologics License Applications from Merck (NYSE:MRK), Seagen (NASDAQ:SGEN), and Astellas (OTCPK:ALPMF)(OTCPK:ALPMY) for a combination of Keytruda (pembrolizumab) and Padcev (enfortumab vedotin) for urothelial cancer.
- https://seekingalpha.com/news/3918891-merck-seagen-astellas-combo-bladder-cancer-treatment-sblas-accepted-by-fda
- Astellas Pharma Inc. (ALPMF), ALPMY, SGEN, MRK
- https://www.padcev.com/
- https://www.keytruda.com/
ENHERTU® (fam-trastuzumab deruxtecan-nxki) for injection
IMJUDO® (tremelimumab) in combination with IMFINZI® (durvalumab)
PADCEV® (enfortumab vedotin-ejfv) with KEYTRUDA® (pembrolizumab)
Enhertu recommended for approval in the EU by CHMP for patients with HER2-low metastatic breast cancer
PUBLISHED19 December 2022 19 December 2022 07:20 GMT
AstraZeneca and Daiichi Sankyo’s Enhertu is the first HER2-directed therapy to
demonstrate a significant survival benefit vs. chemotherapy in this patient population
AstraZeneca and Daiichi Sankyo’s Enhertu (trastuzumab deruxtecan) has been recommended for approval in the European Union (EU) as monotherapy for the treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer who have received prior chemotherapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy.
Enhertu is a specifically engineered HER2-directed antibody drug conjugate (ADC) being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.
The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency based its positive opinion on results from the DESTINY-Breast04 Phase III trial, which were presented at the American Society of Clinical Oncology 2022 Annual Meeting and simultaneously published in The New England Journal of Medicine.1
In the trial, Enhertu reduced the risk of disease progression or death by 50% versus physician’s choice of chemotherapy (based on a hazard ratio [HR] of 0.50; 95% confidence interval [CI]: 0.40-0.63; p<0.001) in patients with HER2-low metastatic breast cancer with HR-positive or HR-negative disease. A median progression-free survival (PFS) of 9.9 months was seen with Enhertu versus 5.1 months in those treated with chemotherapy, as assessed by blinded independent central review (BICR). A 36% reduction in the risk of death (HR 0.64; 95% CI: 0.49-0.84; p=0.001) was seen with Enhertu compared to chemotherapy with a median overall survival (OS) of 23.4 months versus 16.8 months.
Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “Enhertu is the first-ever HER2-directed medicine to show a survival benefit in patients with HER2-low metastatic breast cancer, confirming the importance of targeting lower levels of HER2 expression in patients previously classified as HER2-negative. The CHMP’s recommendation is encouraging and supports our ambition to evolve the way breast cancer is classified and treated to ultimately improve patient outcomes.”
Ken Takeshita, Global Head, R&D Daiichi Sankyo, said: “This positive CHMP opinion recognises the unmet need in the European Union for patients with HER2-low metastatic breast cancer. Currently, once patients with HR-positive disease progress on hormone therapy there are limited effective treatments, and few targeted options are available for patients with HR-negative disease. We look forward to the European Commission decision and aim to bring Enhertu to eligible patients as soon as possible.”
The safety profile observed in patients treated with Enhertu in the DESTINY-Breast04 trial was consistent with that seen in other trials of Enhertu in breast cancer with no new safety signals identified.
Notes
Breast cancer and HER2 expression
Breast cancer is the most common cancer and is one of the leading causes of cancer-related deaths worldwide.2 More than two million patients with breast cancer were diagnosed in 2020 with nearly 685,000 deaths globally.2 In Europe, approximately 531,000 breast cancer patients are diagnosed annually with nearly 141,000 deaths.3
HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumours including breast, gastric, lung and colorectal cancers, and is one of many biomarkers expressed in breast cancer tumours.4
HER2 expression is currently determined by an immunohistochemistry (IHC) test which estimates the amount of HER2 protein on a cancer cell, and/or an in situ hybridisation (ISH) test, which counts the copies of the HER2 gene in cancer cells.4,5 HER2 tests provide IHC and ISH scores across the full HER2 spectrum and are routinely used to determine appropriate treatment options for patients with metastatic breast cancer.
HER2-positive cancers are currently defined as HER2 expression measured as IHC 3+ or IHC 2+/ISH+, and HER2-negative cancers are defined as HER2 expression measured as IHC 0, IHC 1+ or IHC 2+/ISH-.4 However, approximately half of all breast cancers are HER2-low, defined as a HER2 score of IHC1+ or IHC 2+/ISH-.6-8 HER2-low occurs in both HR-positive and HR-negative disease.9
Currently, patients with HR-positive metastatic breast cancer and HER2-low disease have limited effective treatment options following progression on endocrine (hormone) therapy.10 Additionally, few targeted options are available for those with HR-negative disease.11
DESTINY-Breast04
DESTINY-Breast04 is a global, randomised, open-label, Phase III trial evaluating the efficacy and safety of Enhertu (5.4mg/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 randomised 2:1 to receive either Enhertu or chemotherapy.
The primary endpoint of DESTINY-Breast04 is PFS in patients with HR-positive disease based on BICR. Key secondary endpoints include PFS based on BICR in all randomised patients (HR-positive and HR-negative disease), OS in patients with HR-positive disease and OS in all randomised 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.
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 40 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 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 (5.4mg/kg) is approved in Brazil and 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 systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy, based on the results of 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 non-small cell lung cancer 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. 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 adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 and/or the DESTINY-Gastric02 trial.
Enhertu development programme
A comprehensive global development programme 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, are also underway.
Regulatory applications for Enhertu in breast, non-small cell lung and gastric cancer are currently under review in several countries.
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 (DS-1062; 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 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.
With Enhertu (trastuzumab deruxtecan), a HER2-directed ADC, AstraZeneca and Daiichi Sankyo are aiming to improve outcomes in previously treated HER2-positive and HER2-low metastatic breast cancer and are exploring its potential in earlier lines of treatment and in new breast cancer settings.
In HR-positive breast cancer, AstraZeneca continues to improve outcomes with foundational medicines Faslodex (fulvestrant) and Zoladex (goserelin) and aims to reshape the HR-positive space with ngSERD and potential new medicine camizestrant as well as a potential first-in-class AKT kinase inhibitor, capivasertib. AstraZeneca is also collaborating with Daiichi Sankyo to explore the potential of TROP2-directed ADC, datopotamab deruxtecan, in this setting.
PARP inhibitor Lynparza (olaparib) is a targeted treatment option that has been studied in early and metastatic breast cancer with an inherited BRCA mutation. AstraZeneca with MSD (Merck & Co., Inc. in the US and Canada) continue to research Lynparza in these settings and to explore its potential in earlier disease.
To bring much-needed treatment options to patients with triple-negative breast cancer, an aggressive form of breast cancer, AstraZeneca is evaluating the potential of datopotamab deruxtecan alone and in combination with immunotherapy Imfinzi (durvalumab), capivasertib in combination with chemotherapy, and Imfinzi in combination with other oncology medicines, including Lynparza and Enhertu.
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.
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's Enhertu wins EU approval for advanced gastric cancer
Dec. 19, 2022 3:43 PM ET
By: Jonathan Block, SA News Editor1 Comment
- The European Commission has approved AstraZeneca's (NASDAQ:AZN) Enhertu (trastuzumab deruxtecan) as a monotherapy for HER2 positive gastric or gastroesophageal junction adenocarcinoma.
- https://seekingalpha.com/news/3918701-astrazeneca-enhertu-wins-eu-approval-for-advanced-gastric-cancer
- AstraZeneca PLC (AZN)
- https://enhertu.com/en
- Please see full Prescribing Information, including Boxed WARNINGS, and Medication Guide.
IMJUDO® (tremelimumab) in combination with IMFINZI® (durvalumab)
IMJUDO® (tremelimumab) in combination with IMFINZI® (durvalumab)
IMJUDO® (tremelimumab) in combination with IMFINZI® (durvalumab)
Imjudo
tremelimumab
Opinion
On 15 December 2022, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorisation for the medicinal product Imjudo, intended for the treatment of hepatocellular carcinoma. The applicant for this medicinal product is AstraZeneca AB.
Imjudo will be available as a 20 mg/ml concentrate for solution for infusion. The active substance of Imjudo is tremelimumab, a monoclonal antibody (ATC code: L01FX20). It binds to CTLA-4, which is primarily expressed on the surface of activated T lymphocytes, and thus enhances T-cell activation and proliferation, resulting in increased T-cell diversity and enhanced anti-tumour activity.
The benefit of Imjudo in combination with durvalumab is a significant improvement in overall survival compared with the standard of care, sorafenib, as observed in a randomised, open-label, multicentre Phase III study in patients with unresectable hepatocellular carcinoma. The most common side effects are rash, pruritus, diarrhoea, abdominal pain, AST increased, pyrexia, hypothyroidism, cough/productive cough, oedema peripheral and lipase increased.
The full indication is:
Imjudo in combination with durvalumab is indicated for the first line treatment of adults with advanced or unresectable hepatocellular carcinoma (HCC).
Imjudo should be prescribed by physicians experienced in the treatment of cancer.
Detailed recommendations for the use of this product will be described in the summary of product characteristics (SmPC), which will be published in the European public assessment report (EPAR) and made available in all official European Union languages after the marketing authorisation has been granted by the European Commission.
- List itemCHMP summary of positive opinion for Imjudo (PDF/128.42 KB) (new)
Adopted
First published: 16/12/2022
EMA/904398/2022
AstraZeneca's Imjudo combo gets EMA panel nod to treat liver, lung cancers in EU
Dec. 16, 2022 7:01 AM ET
By: Ravikash, SA News Editor
- A panel of the European Medicines Agency (EMA) recommended the approval of AstraZeneca's (NASDAQ:AZN) Imjudo for treating certain types of liver and lung cancers.
- https://seekingalpha.com/news/3917925-astrazenecas-imjudo-combo-gets-ema-panel-nod-to-treat-liver-lung-cancers-in-eu
- AstraZeneca PLC (AZN)
- https://www.imfinzi.com/
- https://www.astrazeneca.com/
DUPIXENT® (DUPILUMAB)
IMJUDO® (tremelimumab) in combination with IMFINZI® (durvalumab)
IMJUDO® (tremelimumab) in combination with IMFINZI® (durvalumab)
December 15, 2022 at 12:59 AM EST
DUPIXENT® (DUPILUMAB) APPROVED BY EUROPEAN COMMISSION AS THE FIRST AND ONLY TARGETED MEDICINE INDICATED FOR PRURIGO NODULARIS
Approval based on direct-to-Phase 3 program showing more than three times as many Dupixent patients (60% and 58%) experienced clinically meaningful itch reduction at 24 weeks compared to placebo (18% and 20%)
Dupixent also significantly reduced skin lesions and improved health-related quality of life compared to placebo
In Europe, about 70,000 adults living with prurigo nodularis are most in need of new treatment options
Dupixent now approved to treat four chronic inflammatory diseases in the EU
TARRYTOWN, N.Y. and PARIS, Dec. 15, 2022 /PRNewswire/ -- Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) and Sanofi today announced that the European Commission (EC) has expanded the marketing authorization for Dupixent® (dupilumab) in the European Union to treat adults with moderate-to-severe prurigo nodularis who are candidates for systemic therapy. 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. With this approval, Dupixent is the first and only targeted medicine specifically indicated to treat prurigo nodularis in Europe and the U.S.
"For the first time, patients with prurigo nodularis in Europe have a medicine that can help relieve the burden of itchy and painful nodules covering their skin, which can have a devastating impact on their day-to-day lives, both physically and mentally," said George D. Yancopoulos, M.D., Ph.D., President and Chief Scientific Officer at Regeneron, and a principal inventor of Dupixent. "Dupixent is now approved for its second dermatological disease and fourth disease overall. We remain committed to further investigating this innovative medicine for diseases – such as chronic urticarias and chronic obstructive pulmonary disease – in which type 2 inflammation may play a role."
"As the first and only targeted medicine approved to treat people living with prurigo nodularis, Dupixent has the potential to transform the standard-of-care for people in Europe living with this debilitating skin disease. In the pivotal trials, patients treated with Dupixent experienced significant improvements in key hallmarks of the disease, such as reduction in itch and achieving clearer skin, as well as broader impacts on their daily lives," Naimish Patel, M.D. Head of Global Development, Immunology and Inflammation at Sanofi. "This approval of Dupixent underscores our continued commitment to bringing Dupixent to patients suffering from chronic skin diseases with underlying type 2 inflammation as quickly as possible."
The EC decision is based on data from two Phase 3 trials, PRIME and PRIME2, evaluating the efficacy and safety of Dupixent (PRIME n=75; PRIME2 n=78) in adults with uncontrolled prurigo nodularis compared to placebo (PRIME n=76; PRIME2 n=82). In these trials, 44% and 37% of Dupixent patients experienced a clinically meaningful reduction in itch at 12 weeks, compared to 16% and 22% for placebo, respectively. The improvement further increased at 24 weeks, with approximately three times as many Dupixent patients (60% and 58%) experiencing a clinically meaningful reduction in itch from baseline, compared to placebo (18% and 20%).
In PRIME and PRIME2, more than twice as many Dupixent patients (48% and 45%) also achieved clear or almost clear skin at 24 weeks, compared to placebo (18% and 16%). Dupixent also significantly improved health-related quality of life, while reducing measures of skin pain and symptoms of anxiety/depression from baseline at 24 weeks compared to placebo.
The safety results of the trial were generally consistent with the known safety profile of Dupixent in its approved indications, with the most common side effects across indications including injection site reactions, conjunctivitis, conjunctivitis allergic, arthralgia, oral herpes and eosinophilia. Adverse events more commonly observed in prurigo nodularis with Dupixent compared to placebo included conjunctivitis (4% Dupixent and 1% placebo).
About Prurigo Nodularis
Prurigo nodularis is a chronic, debilitating skin disease with underlying type 2 inflammation and has one of the highest impacts on a patient's quality of life among inflammatory skin diseases due to the extreme itch it causes. Those with prurigo nodularis experience intense, persistent itch with thick skin lesions (called nodules) that can cover most of the body. The disease is often painful – with burning, stinging and tingling of the skin – and can negatively affect mental health, activities of daily living and social interactions. High-potency topical steroids are commonly prescribed but are associated with safety risks if used long-term. In Europe, about 70,000 adults living with prurigo nodularis are most in need of new treatment options.
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), the proportion of patients who achieved a clinically meaningful response in both WI-NRS and IGA PN-S, improvement from baseline in health-related quality of life (measured by the Dermatology Life Quality Index [DLQI] on a 0-30 scale), improvement from baseline in skin pain (measured by a Numerical Rating Scale from 0-10), and improvement from baseline in symptoms of anxiety and depression (measured by the Hospital Anxiety and Depression Scale [HADS] from 0-42).
About Dupixent
Dupixent is an injection under the skin (subcutaneous injection) at different injection sites. In the EU for adults with prurigo nodularis, Dupixent is administered at 300 mg every two weeks, following a loading dose. It is available as both a pre-filled pen and pre-filled syringe at the 300 mg 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.
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 atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP) and prurigo nodularis, as well as investigational disease eosinophilic esophagitis (EoE) in the EU.
Dupixent has received regulatory approvals in one or more countries around the world for use in certain patients with atopic dermatitis, asthma, CRSwNP, EoE or prurigo nodularis in different age populations. Dupixent is currently approved for one or more of these indications in more than 60 countries, including in Europe, the U.S. and Japan. More than 500,000 patients have been treated with Dupixent globally.
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 EoE, hand and foot atopic dermatitis, chronic inducible urticaria-cold, chronic spontaneous urticaria, chronic pruritus 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 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.
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 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-european-commission-as-the-first-and-only-targeted-medicine-indicated-for-prurigo-nodularis-301703698.html
SOURCE Regeneron Pharmaceuticals, Inc.
Sanofi, Regeneron Dupixent gets approval in EU for expanded use in skin disorder
Dec. 15, 2022 5:02 AM ET
Regeneron Pharmaceuticals, Inc. (REGN), SNY
By: Ravikash, SA News Editor
- The European Commission (EC) approved the expanded use of Sanofi (NASDAQ:SNY) and Regeneron Pharmaceuticals' (NASDAQ:REGN) Dupixent (dupilumab) to treat adults with moderate-to-severe prurigo nodularis (PN) who are candidates for systemic therapy.
- https://seekingalpha.com/news/3917422-sanofiregeneron-dupixent-gets-approval-in-eu-for-expanded-use-in-skin-disorder
- Regeneron Pharmaceuticals, Inc. (REGN), SNY
- https://www.dupixent.com/
- https://www.regeneron.com/
LYNPARZA® (olaparib) in Combination With Abiraterone and Prednisone or Prednisolone
LYNPARZA® (olaparib) in Combination With Abiraterone and Prednisone or Prednisolone
LYNPARZA® (olaparib) in Combination With Abiraterone and Prednisone or Prednisolone
AstraZeneca and Merck Provide Update on US Regulatory Review of LYNPARZA® (olaparib) in Combination With Abiraterone and Prednisone or Prednisolone as Treatment of Metastatic Castration-Resistant Prostate Cancer
December 15, 2022 6:45 am ET
RAHWAY, N.J.--(BUSINESS WIRE)-- AstraZeneca and Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced that the U.S. Food and Drug Administration (FDA) has informed AstraZeneca that the agency will extend by three months the Prescription Drug User Fee Act (PDUFA) date for the pending supplemental new drug application (sNDA) for LYNPARZA in combination with abiraterone and prednisone or prednisolone for the treatment of adult patients with metastatic castration-resistant prostate cancer (mCRPC). The purpose of the extension is to provide further time for the full review of the submission. The companies will continue to work with the FDA to facilitate the completion of the agency’s review.
The sNDA for LYNPARZA in combination with abiraterone and prednisone or prednisolone is based on the Phase 3 PROpel trial, results of which were published in NEJM Evidence in June 2022. The application was granted priority review, and AstraZeneca and Merck are committed to working with the FDA to bring this treatment option to patients with mCRPC.
In November, the European Medicines Agency’s Committee for Medicinal Products for Human Use adopted a positive opinion recommending approval of LYNPARZA in combination with abiraterone and prednisone or prednisolone in the European Union (EU) for the treatment of adult patients with mCRPC for whom chemotherapy is not clinically indicated. This combination is also undergoing regulatory reviews in other countries.
Approved indications for LYNPARZA are not impacted by this review period extension. Among these, LYNPARZA is approved in the U.S. for patients with homologous recombination repair (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 (NHA). These approvals were based on the data from the Phase 3 PROfound trial.
About PROpel
PROpel is a randomized, double-blind Phase 3 trial testing the efficacy, safety and tolerability of LYNPARZA versus placebo when given in addition to abiraterone and prednisone or prednisolone in patients with mCRPC who had not received prior chemotherapy or NHAs in the mCRPC setting. The major efficacy outcome was radiographic progression-free survival as assessed by investigator per RECIST v1.1 and Prostate Cancer Working Group (bone) criteria. Overall survival was an additional efficacy outcome measure.
INDICATIONS for LYNPARZA in the United States
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.
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 .
About LYNPARZA® (olaparib)
LYNPARZAis a first-in-class PARP inhibitor and the first targeted treatment to potentially exploit DNA damage response (DDR) pathway deficiencies, such as BRCA mutations, to preferentially kill cancer cells. 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 tumor types with defects and dependencies in the DDR.
LYNPARZA, which is being jointly developed and commercialized by AstraZeneca and Merck, has a broad clinical trial development program, and AstraZeneca and Merck are working together to understand how it may affect multiple PARP-dependent tumors as a monotherapy and in combination across multiple cancer types.
About the AstraZeneca and Merck strategic oncology collaboration
In July 2017, AstraZeneca and Merck, known as MSD outside of the United States and Canada, announced a global strategic oncology collaboration to co-develop and co-commercialize certain oncology products including LYNPARZA, the world’s first PARP inhibitor, for multiple cancer types. Working together, the companies will developthese products in combination with other potential new medicines and as monotherapies. Independently, the companies will develop these oncology products in combination with their respective PD-L1 and PD-1 medicines.
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.
Source: Merck & Co., Inc.
FDA extends review of AstraZeneca/Merck's Lynparza's expanded use in prostate cancer
Dec. 15, 2022 4:34 AM ET
AstraZeneca PLC (AZN), MRK, JNJ
By: Ravikash, SA News Editor
The U.S. Food and Drug Administration (FDA) will extend the review period by three months of AstraZeneca (NASDAQ:AZN) and Merck's (NYSE:MRK) Lynparza to treat a type of prostate cancer to have more time to review the companies' application.
ADCETRIS® (brentuximab vedotin) with Novel Immunotherapy Combination
LYNPARZA® (olaparib) in Combination With Abiraterone and Prednisone or Prednisolone
LYNPARZA® (olaparib) in Combination With Abiraterone and Prednisone or Prednisolone
Seagen Announces Results from Phase 2 Clinical Trial of ADCETRIS® (brentuximab vedotin) with Novel Immunotherapy Combination in Patients with Advanced- and Early-Stage Classical Hodgkin Lymphoma
12/12/2022
– ADCETRIS in Combination with Nivolumab, Doxorubicin and Dacarbazine Delivers 88% Complete Response (CR) Rate in Advanced-Stage cHL and 92% CR Rate in Early-Stage cHL –
– 95% of Advanced-Stage Patients Remain Progression Free at 12 Months with 17 Months Median Follow-Up –
– Regimen Was Well-Tolerated in Both Cohorts with No Treatment-Related Deaths and Less Than Half of Patients in Either Group Developed Any Grade Peripheral Sensory Neuropathy –
BOTHELL, Wash.--(BUSINESS WIRE)-- Seagen Inc. (Nasdaq: SGEN) today announced results from two parts of a phase 2 trial (SGN35-027) evaluating ADCETRIS® (brentuximab vedotin) in combination with the PD-1 inhibitor nivolumab and standard chemotherapy agents doxorubicin and dacarbazine (AN+AD) for the frontline treatment of patients with classical Hodgkin lymphoma (cHL). Part B of the trial evaluated patients with advanced-stage disease and was presented as an oral presentation, and Part C evaluated patients with early-stage disease and was presented as a poster at the 64th American Society of Hematology (ASH) Annual Meeting and Exposition in New Orleans.
Results demonstrated a complete response (CR) rate of 88% and an overall response rate (ORR) of 93% in patients with advanced-stage disease (Part B), and a CR rate of 92% and an ORR of 95% in patients with early-stage disease (Part C). The data showed that the combination was well-tolerated, with no new safety signals observed.
“We are encouraged that ADCETRIS in combination with the immunotherapy nivolumab and standard chemotherapy agents showed promising efficacy and safety as a first-line treatment in patients with early- and advanced-stage classical Hodgkin lymphoma,” said Marjorie Green, M.D., Senior Vice President and Head of Late-Stage Development at Seagen. “These agents with complementary mechanisms of action warrant further investigation as a potential frontline treatment option for patients with Hodgkin lymphoma.”
Part B Phase 2 Study of Brentuximab Vedotin, Nivolumab, Doxorubicin, and Dacarbazine (AN+AD) for Advanced Stage Classic Hodgkin Lymphoma (Abstract #314)
Part B of SGN35-027 is evaluating the novel ADCETRIS combination in 57 patients with advanced-stage cHL (Stage II with bulky disease, Stage III or IV). Results showed:
- An 88% CR rate (95% Confidence Interval [CI]: 76.3, 94.9) and 93% ORR (95% CI: 83.0, 98.1) at the end of treatment.
- The estimated 12-month progression-free survival (PFS) rate was 95% (median follow-up 17.2 months [95% CI: 15.5, 17.5]).
- The most frequently reported treatment-related treatment-emergent adverse events (TEAEs) occurring in more than 40% of patients were nausea at 65% (37/57), fatigue at 47% (27/57) and peripheral sensory neuropathy at 44% (25/57).
- Peripheral sensory neuropathy was primarily low grade (4% Grade ≥3), and no patients discontinued due to peripheral sensory neuropathy.
Part C Phase 2 Study of Brentuximab Vedotin, Nivolumab, Doxorubicin, and Dacarbazine (AN+AD) for Early-Stage Classic Hodgkin Lymphoma (Abstract #4230)
Part C of SGN35-027 is evaluating the novel ADCETRIS combination in 125 patients with early-stage (non-bulky Stage I or II) cHL. Of 125 patients in the study, 76 were included at the time of efficacy assessment. Results showed:
- A 92% CR rate (95% CI: 83.6, 97.0) and a 95% ORR (95% CI: 87.1, 98.5) at end of treatment (N=76).
- Follow up is ongoing and PFS results are not yet available.
- The most frequently reported treatment-related TEAEs occurring in more than 30% of patients were nausea at 68% (85/125), peripheral sensory neuropathy at 42% (53/125), and fatigue at 38% (47/125).
- Peripheral sensory neuropathy was primarily low grade (2% Grade ≥3), and no patients discontinued due to peripheral sensory neuropathy.
About the SGN35-027 Clinical Study
SGN35-027 is an ongoing open-label, multiple part, multicenter, phase 2 clinical trial evaluating two brentuximab vedotin treatment combinations in patients with advanced and early-stage cHL. The trial includes three parts (Parts A, B, and C). Part A includes a combination of brentuximab vedotin and doxorubicin, vinblastine and dacarbazine (A+AVD), while Parts B and C include brentuximab vedotin in combination with nivolumab, doxorubicin, and dacarbazine (AN+AD). The primary endpoint for Part A is the proportion of patients with treatment-emergent febrile neutropenia. The primary endpoint for Parts B and C is the proportion of participants with complete response at end of treatment according to the Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC). Incidence of adverse events is a secondary endpoint for Parts B and C.
About ADCETRIS
ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, a defining marker of cHL and expressed on the surface of several types of lymphomas. It is approved in seven indications in the U.S.:
- Adult patients with previously untreated Stage III/IV cHL, in combination with doxorubicin, vinblastine, and dacarbazine.
- Pediatric patients 2 years and older with previously untreated high risk cHL, in combination with doxorubicin, vincristine, etoposide, prednisone and cyclophosphamide.
- Adult patients with cHL at high risk of relapse or progression as post-autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation.
- Adult patients with cHL after failure of auto-HSCT or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates.
- Adult patients with previously untreated systemic anaplastic large cell lymphoma (sALCL) or other CD30-expressing peripheral T-cell lymphomas (PTCL), including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified, in combination with cyclophosphamide, doxorubicin, and prednisone.
- Adult patients with sALCL after failure of at least one prior multi-agent chemotherapy regimen.
- Adult patients with primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy.
Seagen and Takeda jointly develop ADCETRIS. Under the terms of the collaboration agreement, Seagen has U.S. and Canadian commercialization rights, and Takeda has rights to commercialize ADCETRIS in the rest of the world. Seagen recognizes royalty revenues from Takeda based on a percentage of Takeda's net sales of ADCETRIS in its licensed territories based on annual net sales tiers. Seagen and Takeda are funding joint development costs for ADCETRIS on a 50:50 basis, except in Japan where Takeda is solely responsible for development costs.
ADCETRIS® (brentuximab vedotin) for injection U.S. Important Safety Information
BOXED WARNING
PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML): JC virus infection resulting in PML and death can occur in ADCETRIS-treated patients.
CONTRAINDICATION
Contraindicated with concomitant bleomycin due to pulmonary toxicity (e.g., interstitial infiltration and/or inflammation)
Please see full Prescribing information, including BOXED WARNING, for ADCETRIS here.
View source version on businesswire.com: https://www.businesswire.com/news/home/20221212005222/en/
Source: Seagen Inc.
Seagen buoyed by Adcetris combo data for classical Hodgkin lymphoma
Dec. 12, 2022 1:50 PM ET
By: Jonathan Block, SA News Editor
- Phase 2 data of Seagen's (NASDAQ:SGEN) Adcetris (brentuximab vedotin) in combination with Bristol-Myers Squibb's (BMY) Opdivo (nivolumab) and standard chemotherapy agents in patients with classical Hodgkin lymphoma led to improved complete response.
- https://seekingalpha.com/news/3916234-seagen-buoyed-by-adcetris-combo-data-for-classical-hodgkin-lymphoma
- Seagen Inc. (SGEN)
- https://www.adcetris.com/
- https://www.seagen.com/
Jardiance® (empagliflozin)
LYNPARZA® (olaparib) in Combination With Abiraterone and Prednisone or Prednisolone
KEYTRUDA® (pembrolizumab) combined with chemotherapy
Phase III trial demonstrated Jardiance® is the first SGLT2 inhibitor to show statistically significant reduction in blood sugar levels in children and adolescents with type 2 diabetes
December 7, 2022
- Jardiance® (empagliflozin) is the first SGLT2 inhibitor to demonstrate a statistically significant reduction in the primary outcome of HbA1c (a marker of average blood sugar) in participants aged 10-17 living with type 2 diabetes compared to placebo
- Safety data in this vulnerable population was similar to that in adults with type 2 diabetes, confirming the well-established safety profile of Jardiance
INGELHEIM, Germany and RIDGEFIELD, Conn. and INDIANAPOLIS, Dec. 7, 2022 /PRNewswire/ -- The DINAMO phase III clinical trial met its primary endpoint by demonstrating a statistically significant reduction in HbA1c (a marker of average blood sugar) with Jardiance® (empagliflozin) compared with placebo for children and adolescents aged 10-17 years living with type 2 diabetes. When Jardiance was added to other baseline treatments (diet, exercise, metformin and/or insulin) HbA1c was reduced by 0.84% compared with placebo at week 26 (95% CI –1.50 to –0.19; P=0.012). The results were presented today at the International Diabetes Federation (IDF) World Diabetes congress 2022, Boehringer Ingelheim and Eli Lilly and Company (NYSE: LLY) announced.
The DINAMO (DIabetes study of liNAgliptin and eMpagliflozin in children and adOlescents) trial included youth aged 10-17 years with type 2 diabetes and HbA1c ≥6.5% and ≤10.5%. Participants were randomly assigned treatment with Jardiance (10 or 25 mg) (n=52), Tradjenta® (linagliptin) (5 mg) (n=53) or placebo (n=53) once daily. All participants were treated with diet and exercise plus, when appropriate, metformin and/or insulin.
The overall safety data was generally consistent with previous findings in adults with type 2 diabetes, confirming the well-established safety profile of both Jardiance and Tradjenta.
"Across the lifespan, we know that people living with type 2 diabetes have a high risk for many diabetes complications, so it's important to recognize and treat diabetes early in its course," said Lori Laffel, M.D., principal investigator of the DINAMO study and chief of the Pediatric, Adolescent, and Young Adult Section at the Joslin Diabetes Center and professor of pediatrics at Harvard Medical School. "Today's results from the DINAMO global clinical trial demonstrated that the SGLT2 inhibitor Jardiance compared with placebo significantly improved overall blood sugar control in children and adolescents with type 2 diabetes. These findings are particularly important given the need for more therapeutic options, especially oral agents, to manage type 2 diabetes in young people as, to date, metformin is the only globally available oral treatment for youth."
A secondary endpoint from the trial showed that at week 26, Jardiance reduced fasting plasma glucose (–35.2 mg/dL; P=0.0035).
"With more than 41,000 new cases worldwide annually, type 2 diabetes in today's young people is a global public health issue, especially in light of the rise of risk factors such as obesity," said Lykke Hinsch Gylvin, M.D., chief medical officer at Boehringer Ingelheim. "The clinically meaningful benefit and consistent safety profile demonstrated with Jardiance in the DINAMO trial is an encouraging outcome for the vulnerable population of children and adolescents."
"The rise in the prevalence of type 2 diabetes in the pediatric population highlights a clear unmet need," said Jeff Emmick, M.D., Ph.D., vice president, Product Development, Eli Lilly & Company. "Having overcome the challenges in recruitment and design that pediatric trials tend to face, the outcomes of DINAMO represent another positive step forward in Boehringer Ingelheim and Lilly's commitment to improve the lives of people living with cardio-renal and metabolic conditions such as type 2 diabetes."
Reduction in HbA1c in participants treated with Tradjenta was not statistically significant when compared with placebo. A numerical reduction of 0.34% (P=0.2935) was observed.
The findings have been submitted for publication in a peer-reviewed journal.
About DINAMO: DIabetes study of liNAgliptin and eMpagliflozin in children and adOlescents
DINAMO (NCT03429543) enrolled children and adolescents aged 10-17 years with type 2 diabetes (HbA1c ≥6.5% and ≤10.5%). Of the 262 participants screened, 158 were randomly assigned to treatment with Jardiance (10 or 25 mg) (n=52), Tradjenta (5 mg) (n=53) or placebo (n=53) once daily. All participants were treated with diet and exercise plus metformin and/or insulin (or no background if metformin intolerant). The trial compared efficacy and safety of a Jardiance dosing regimen compared with placebo and Tradjenta compared with placebo on durable glycemic control in youth with type 2 diabetes.
What is JARDIANCE?
JARDIANCE is a prescription medicine used to:
- reduce the risk of cardiovascular death and hospitalization for heart failure in adults with heart failure, when the heart cannot pump enough blood to the rest of your body
- reduce the risk of cardiovascular death in adults with type 2 diabetes who also have known cardiovascular disease
- lower blood sugar along with diet and exercise in adults with type 2 diabetes
JARDIANCE is not for people with type 1 diabetes. It may increase their risk of diabetic ketoacidosis (increased ketones in the blood or urine).
JARDIANCE is not for use to lower blood sugar in adults with type 2 diabetes who have severe kidney problems, because it may not work.
https://www.jardiance.com/type-2-diabetes/
For more information, please see Prescribing Information and Medication Guide.
CL-JAR-100131 10.17.2022
Boehringer Ingelheim and Eli Lilly and Company
In January 2011, Boehringer Ingelheim and Eli Lilly and Company announced an Alliance that centers on compounds representing several of the largest diabetes treatment classes. Depending on geographies, the companies either co-promote or separately promote the respective molecules each contributing to the Alliance. The Alliance leverages the strengths of two of the world's leading pharmaceutical companies to focus on patient needs. By joining forces, the companies demonstrate their commitment, not only to the care of people with diabetes, but also to investigating the potential to address areas of unmet medical need.
About Boehringer Ingelheim
Boehringer Ingelheim is working on breakthrough therapies that improve the lives of humans and animals. As a leading research-driven biopharmaceutical company, the company creates value through innovation in areas of high unmet medical need. Founded in 1885 and family-owned ever since, Boehringer Ingelheim takes a long-term perspective. Around 52,000 employees serve more than 130 markets in the three business areas, Human Pharma, Animal Health, and Biopharmaceutical Contract Manufacturing. Learn more at www.boehringer-ingelheim.us.
About Eli Lilly and Company
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 and LinkedIn.
This press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about Jardiance® as a treatment for adults with type 2 diabetes, to reduce the risk of cardiovascular death in adults with type 2 diabetes and known cardiovascular disease, and to reduce the risk of cardiovascular death and hospitalization for heart failure in adults with heart failure, and as a potential treatment for adults with cardio-kidney-metabolic conditions and reflects Lilly's current beliefs and expectations. However, as with any pharmaceutical product, there are substantial risks and uncertainties in the process of drug research, development and commercialization. Among other things, there can be no guarantee that planned or ongoing studies will be completed as planned, that future study results will be consistent with the results to date or that Jardiance® will receive additional regulatory approvals. For a further discussion of these and other risks and uncertainties that could cause actual results to differ from Lilly's expectations, please see Lilly's most recent Forms 10-K and 10-Q filed with the U.S. Securities and Exchange Commission. Lilly undertakes no duty to update forward-looking statements.
Jardiance®, EMPEROR-Reduced®, EMPEROR-Preserved®, EMPA-REG OUTCOME® and EMPACT-MI® are registered trademarks of Boehringer Ingelheim.
View original content to download multimedia:https://www.prnewswire.com/news-releases/phase-iii-trial-demonstrated-jardiance-is-the-first-sglt2-inhibitor-to-show-statistically-significant-reduction-in-blood-sugar-levels-in-children-and-adolescents-with-type-2-diabetes-301697025.html
SOURCE Eli Lilly and Company
Lilly, Boehringer diabetes drug meets main goal in patients aged 10-17
Dec. 07, 2022 8:48 AM ET
By: Dulan Lokuwithana, SA News Editor
- Eli Lilly (NYSE:LLY) and its German partner Boehringer Ingelheim announced Wednesday that the Phase 3 trial for SGLT2 inhibitor Jardiance met the primary endpoint in patients aged 10-17 years with type 2 diabetes.
- https://seekingalpha.com/news/3914862-lly-stock-on-watch-as-diabetes-drug-meets-main-goal-in-young-patients
- Eli Lilly and Company (LLY)
- https://www.jardiance.com/type-2-diabetes/
- https://www.lilly.com/
KEYTRUDA® (pembrolizumab) combined with chemotherapy
ENHERTU® (fam-trastuzumab deruxtecan-nxki) for injection
KEYTRUDA® (pembrolizumab) combined with chemotherapy
Merck Announces Phase 3 KEYNOTE-859 Trial Met Primary Endpoint of Overall Survival in Patients With HER2-Negative Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma
November 22, 2022 6:45 am ET
In KEYNOTE-859, KEYTRUDA® (pembrolizumab) combined with chemotherapy demonstrated statistically significant overall survival, progression-free survival, and overall response rate for patients regardless of PD-L1 expression
RAHWAY, N.J.--(BUSINESS WIRE)-- Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced positive topline results from the pivotal Phase 3 KEYNOTE-859 trial investigating KEYTRUDA, Merck’s anti-PD-1 therapy, in combination with chemotherapy for the first-line treatment of patients with human epidermal growth factor receptor 2 (HER2)-negative locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma. KEYTRUDA in combination with chemotherapy showed a statistically significant and clinically meaningful improvement in the trial’s primary endpoint of overall survival (OS) versus chemotherapy alone in the all-randomized patient population at a pre-specified interim analysis conducted by an independent Data Monitoring Committee. Statistically significant and clinically meaningful improvements in progression-free survival (PFS) and overall response rate (ORR) were also observed in the all-randomized patient population.
The safety profile of KEYTRUDA in this trial was consistent with that observed in previously reported studies; no new safety signals were identified. Results will be presented at an upcoming medical meeting and will be submitted to regulatory authorities.
“Despite improvements in cancer care, advanced gastric cancer continues to have one of the lowest five-year survival rates, and new interventions are urgently needed. The results from KEYNOTE-859 show the potential of KEYTRUDA plus chemotherapy to improve survival beyond chemotherapy alone for patients with HER2-negative locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma, regardless of PD-L1 expression,” said Dr. Eliav Barr, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories. “We are excited by these new results that demonstrate our commitment to exploring new treatment options for patients fighting gastrointestinal cancers with KEYTRUDA and thank all investigators and patients who participated in this trial.”
Merck has an extensive clinical development program evaluating KEYTRUDA in gastrointestinal cancers, which includes KEYNOTE-811 in first-line advanced HER2-positive gastric cancer, KEYNOTE-585 in early-stage gastric cancer, and further exploration in advanced/metastatic gastric cancer in LEAP-015. Merck is continuing to study KEYTRUDA for multiple uses in hepatobiliary, esophageal, pancreatic and colorectal cancers.
About KEYNOTE-859
KEYNOTE-859 is a randomized, double-blind Phase 3 trial (ClinicalTrials.gov, NCT03675737) evaluating KEYTRUDA in combination with chemotherapy compared to placebo in combination with chemotherapy for the first-line treatment of patients with HER2-negative locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma. The primary endpoint is OS, and secondary endpoints include PFS, ORR, duration of response and safety. The trial enrolled 1,579 patients who were randomized to receive KEYTRUDA (200 mg every three weeks for up to approximately two years) in combination with fluoropyrimidine- and platinum-containing chemotherapy, or placebo in combination with chemotherapy.
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.
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's Keytruda shows survival benefit, meets main goal of gastric cancer trial
Nov. 22, 2022 7:18 AM ET
By: Ravikash, SA News Editor2 Comments
Merck's (NYSE:MRK) blockbuster drug Keytruda, in combination with chemotherapy, met the main goal of overall survival (OS) in patients with a type of gastric cancer in a phase 3 trial.
ENHERTU® (fam-trastuzumab deruxtecan-nxki) for injection
ENHERTU® (fam-trastuzumab deruxtecan-nxki) for injection
ENHERTU® (fam-trastuzumab deruxtecan-nxki) for injection
Enhertu
trastuzumab deruxtecan
Table of contents
Opinion
On 10 November 2022, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending a change to the terms of the marketing authorisation for the medicinal product Enhertu. The marketing authorisation holder for this medicinal product is Daiichi Sankyo Europe GmbH.
The CHMP adopted a new indication for the treatment of gastric cancer. For information, the full indications for Enhertu will therefore be as follows:1
Breast cancer
Enhertu as monotherapy is indicated for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received one or more prior anti-HER2-based regimens.
Gastric cancer
Enhertu as monotherapy is indicated for the treatment of adult patients with advanced HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen.
Detailed recommendations for the use of this product will be described in the updated summary of product characteristics (SmPC), which will be published in the revised European public assessment report (EPAR), and will be available in all official European Union languages after a decision on this change to the marketing authorisation has been granted by the European Commission.
1 New text in bold.
- List itemCHMP post-authorisation summary of positive opinion for Enhertu (II-12) (PDF/125.65 KB) (new)
Adopted
First published: 11/11/2022
Daiichi Sankyo wins EU backing for Enhertu in gastric cancer
Nov. 11, 2022 8:50 AM ET
Daiichi Sankyo Company, Limited (DSKYF), DSNKY, AZN
By: Dulan Lokuwithana, SA News Editor
- An expert panel of the European Medicines Agency (EMA) has recommended issuing marketing authorization for Daiichi Sankyo (OTCPK:DSKYF) (OTCPK:DSNKY) to include gastric cancer as an indication for Enhertu, an antibody-drug conjugate the company develops with AstraZeneca (NASDAQ:AZN).
- https://seekingalpha.com/news/3906414-daiichi-sankyo-wins-eu-backing-for-enhertu-in-gastric-cancer
- Daiichi Sankyo Company, Limited (DSKYF), DSNKY, AZN
- https://enhertu.com/en
- https://www.daiichisankyo.com/
LYNPARZA® (olaparib) tablets
ENHERTU® (fam-trastuzumab deruxtecan-nxki) for injection
ENHERTU® (fam-trastuzumab deruxtecan-nxki) for injection
LYNPARZA® (olaparib) tablets
Lynparza
olaparib
Table of contents
Opinion
On 10 November 2022, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending a change to the terms of the marketing authorisation for the medicinal product Lynparza. The marketing authorisation holder for this medicinal product is AstraZeneca AB.
The CHMP adopted a new indication as follows:
Lynparza is indicated in combination with abiraterone and prednisone or prednisolone for the treatment of adult patients with mCRPC in whom chemotherapy is not clinically indicated (see section 5.1).
For information, the full indications for Lynparza tablets will therefore be as follows:1
Ovarian cancer
Lynparza is indicated as monotherapy for the:
- maintenance treatment of adult patients with advanced (FIGO stages III and IV) BRCA1/2-mutated (germline and/or somatic) high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer who are in response (complete or partial) following completion of first-line platinum-based chemotherapy.
- maintenance treatment of adult patients with platinum‑sensitive relapsed high‑grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) to platinum‑based chemotherapy.
Lynparza in combination with bevacizumab is indicated for the:
- maintenance treatment of adult patients with advanced (FIGO stages III and IV) high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer who are in response (complete or partial) following completion of first-line platinum-based chemotherapy in combination with bevacizumab and whose cancer is associated with homologous recombination deficiency (HRD) positive status defined by either a BRCA1/2 mutation and/or genomic instability (see section 5.1).
Breast cancer
Lynparza is indicated as:
- monotherapy or in combination with endocrine therapy for the adjuvant treatment of adult patients with germline BRCA1/2-mutations who have HER2-negative, high risk early breast cancer previously treated with neoadjuvant or adjuvant chemotherapy (see sections 4.2 and 5.1).
- monotherapy for the treatment of adult patients with germline BRCA1/2-mutations, who have HER2 negative locally advanced or metastatic breast cancer. Patients should have previously been treated with an anthracycline and a taxane in the (neo)adjuvant or metastatic setting unless patients were not suitable for these treatments (see section 5.1). Patients with hormone receptor (HR)-positive breast cancer should also have progressed on or after prior endocrine therapy, or be considered unsuitable for endocrine therapy.
Adenocarcinoma of the pancreas
Lynparza is indicated as monotherapy for the maintenance treatment of adult patients with germline BRCA1/2-mutations who have metastatic adenocarcinoma of the pancreas and have not progressed after a minimum of 16 weeks of platinum treatment within a first-line chemotherapy regimen.
Prostate cancer
Lynparza is indicated:
- as monotherapy for the treatment of adult patients with metastatic castration-resistant prostate cancer (mCRPC) and BRCA1/2-mutations (germline and/or somatic) who have progressed following prior therapy that included a new hormonal agent.
- in combination with abiraterone and prednisone or prednisolone for the treatment of adult patients with mCRPC in whom chemotherapy is not clinically indicated (see section 5.1).
Detailed recommendations for the use of this product will be described in the updated summary of product characteristics (SmPC), which will be published in the revised European public assessment report (EPAR), and will be available in all official European Union languages after a decision on this change to the marketing authorisation has been granted by the European Commission.
1New text in bold
- List itemCHMP post-authorisation summary of positive opinion for Lynparza (II-53) (PDF/151.54 KB) (new)
First published: 11/11/2022 EMA/CHMP/822269/2022
AstraZeneca/Merck's Lynparza gets EMA panel's greenlight for expanded use in prostate cancer
Nov. 11, 2022 8:35 AM ET
By: Ravikash, SA News Editor
- A panel of the European Medicines Agency (EMA) recommended the expanded approval of AstraZeneca (NASDAQ:AZN) and Merck's (NYSE:MRK) blockbuster cancer drug Lynparza.
- https://seekingalpha.com/news/3906396-astrazenecamercks-lynparza-gets-ema-panels-greenlight-for-expanded-use-in-prostate-cancer
- AstraZeneca PLC (AZN), MRK
- https://www.lynparza.com/
- https://www.merck.com/
- https://www.astrazeneca.com/
BIOTECNOVA™
Imfinzi(durvalumab) and Imjudo(tremelimumab) with chemotherapy
Imfinzi(durvalumab) and Imjudo(tremelimumab) with chemotherapy
Imfinzi(durvalumab) and Imjudo(tremelimumab) with chemotherapy
Imfinzi and Imjudo with chemotherapy approved in the US for patients with metastatic non-small cell lung cancer
PUBLISHED11 November 2022 11 November 2022 07:00 GMT
Approval based on POSEIDON Phase III trial results, which showed significant survival benefit with a limited course of Imjudo added to Imfinzi and chemotherapy
AstraZeneca’s Imfinzi (durvalumab) in combination with Imjudo (tremelimumab) plus platinum-based chemotherapy has been approved in the US for the treatment of adult patients with Stage IV (metastatic) non-small cell lung cancer (NSCLC).
The approval by the Food and Drug Administration (FDA) was based on the results from the POSEIDON Phase III trial. Patients treated with a limited course of five cycles of the anti-CTLA-4 antibody Imjudo added to Imfinzi plus four cycles of platinum-based chemotherapy experienced a 23% reduction in the risk of death versus a range of chemotherapy options (based on a hazard ratio [HR] of 0.77; 95% CI 0.65-0.92; p=0.00304). An estimated 33% of patients were alive at two years versus 22% for chemotherapy. This treatment combination also reduced the risk of disease progression or death by 28% compared to chemotherapy alone (HR 0.72; 95% CI 0.60-0.86; p=0.00031).
Updated results from the POSEIDON Phase III trial after approximately four years of follow-up presented at the European Society of Medical Oncology (ESMO) Congress 2022 and published in the Journal of Clinical Oncology demonstrated sustained survival benefit, improving overall survival (OS) by 25% compared to chemotherapy alone (HR 0.75; 95% CI 0.63-0.88). An estimated 25% of patients treated with the combination were alive at three years versus 13.6% for those treated with chemotherapy alone. The safety profile for Imjudo plus Imfinzi and chemotherapy was consistent with the known profiles of each medicine, and no new safety signals were identified.
In the US, lung cancer is the second most commonly diagnosed cancer, with more than 236,000 patients expected to be diagnosed in 2022.1 For patients with metastatic NSCLC, prognosis is particularly poor, as only approximately 8% will live beyond five years after diagnosis.2
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 remains a significant treatment challenge because many patients’ tumours do not respond well to standard therapies, including checkpoint inhibitors. The approval of this dual immunotherapy regimen with chemotherapy introduces a new, generally well-tolerated treatment option for patients with this devastating disease and gives them the chance to benefit from the long-term survival advantage seen with CTLA-4 inhibition.”
Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: “This approval underscores the importance of delivering novel treatment combinations that extend survival in metastatic non-small cell lung cancer, a complex setting where many patients still face a dismal prognosis. This marks the second indication for Imjudo added to Imfinzi in just a few weeks following its approval in unresectable liver cancer, reinforcing the benefits of this new medicine and our commitment to improving patient outcomes in cancer settings with continued unmet need.”
Regulatory applications are also currently under review in Europe, Japan and several other countries for this indication based on the POSEIDON results.
Imfinzi is the only approved immunotherapy and the global standard of care in the curative-intent setting of unresectable, Stage III NSCLC in patients whose disease has not progressed after chemoradiation therapy based on the PACIFIC Phase III trial. Imfinzi is also approved in the US, the 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. Imfinzi is approved in the US and several other countries in combination with chemotherapy for the treatment of locally advanced or metastatic biliary tract cancer based on the TOPAZ-1 Phase III trial, and it is approved with Imjudo in the US for the treatment of unresectable hepatocellular carcinoma based on the HIMALAYA Phase III trial.
Notes
Stage IV NSCLC
Lung cancer is the second most common form of cancer globally, with more than two million patients diagnosed in 2020.3 Lung cancer is broadly split into NSCLC and SCLC, with 80-85% classified as NSCLC. Within NSCLC, patients are classified as squamous, representing 25-30% of patients, or non-squamous, in approximately 70-75% of patients.4-6
POSEIDON
The POSEIDON trial was a randomised, open-label, multi-centre, global, Phase III trial of Imfinzi plus platinum-based chemotherapy, or Imfinzi, Imjudo 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 Imjudo 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 Imjudo 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 progression-free survival (PFS) and OS for the Imfinzi plus chemotherapy arm. Key secondary endpoints included PFS and OS in the Imfinzi plus Imjudo and chemotherapy arm. As both PFS endpoints were met for Imfinzi plus chemotherapy and Imfinzi, Imjudo and chemotherapy, the prespecified statistical analysis plan allowed for testing OS in the Imfinzi plus Imjudo 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.
In addition to its approved indications in lung cancer, Imfinzi is also the only approved immunotherapy in unresectable or metastatic biliary tract cancer and hepatocellular carcinoma (in combination with Imjudo), and is also approved for previously treated patients with advanced bladder cancer in several countries.
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 gastrointestinal (GI) cancers, ovarian cancer, endometrial cancer and other solid tumours.
Imjudo
Imjudo (tremelimumab) is a human monoclonal antibody that targets the activity of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). Imjudo blocks the activity of CTLA-4, contributing to T-cell activation, priming the immune response to cancer and fostering cancer cell death.
Imjudo is also approved in combination with Imfinzi for the treatment of unresectable hepatocellular carcinoma (HCC) and is being tested in combination with Imfinzi across multiple tumour types including locoregional HCC (EMERALD-3), SCLC (ADRIATIC) and bladder cancer (VOLGA and NILE).
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 Imjudo (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 in immuno-oncology (IO)
AstraZeneca has a comprehensive and diverse IO portfolio and pipeline anchored in immunotherapies designed to overcome evasion of the anti-tumour immune response and stimulate the body’s immune system to attack tumours.
AstraZeneca aims to reimagine cancer care and help transform outcomes for patients with Imfinzi as a single treatment and in combination with Imjudo as well as other novel immunotherapies and modalities. The Company is also exploring next-generation immunotherapies like bispecific antibodies and therapeutics that harness different aspects of immunity to target cancer.
AstraZeneca is boldly pursuing an innovative clinical strategy to bring IO-based therapies that deliver long-term survival to new settings across a wide range of cancer types. With an extensive clinical programme, the Company also champions the use of IO treatment in earlier disease stages, where there is the greatest potential for cure.
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.
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 Imjudo, Imfinzi combo approved for non–small cell lung cancer
Nov. 10, 2022 6:17 PM ET
By: Jonathan Block, SA News Editor1 Comment
- The US FDA has approved a combination of AstraZeneca's (NASDAQ:AZN) Imjudo (tremelimumab) + Imfinzi (durvalumab) and platinum-based chemotherapy for metastatic non–small cell lung cancer.
- https://seekingalpha.com/news/3906194-astrazeneca-imjudo-imfinzi-combo-approved-for-nonsmall-cell-lung-cancer
- AstraZeneca PLC (AZN)
- https://www.imfinzi.com/
- https://www.astrazeneca.com/
LIBTAYO® (CEMIPLIMAB-RWLC) IN COMBINATION WITH CHEMOTHERAPY
Imfinzi(durvalumab) and Imjudo(tremelimumab) with chemotherapy
Imfinzi(durvalumab) and Imjudo(tremelimumab) with chemotherapy
November 8, 2022 at 4:41 PM EST
LIBTAYO® (CEMIPLIMAB-RWLC) IN COMBINATION WITH CHEMOTHERAPY APPROVED BY THE FDA AS FIRST-LINE TREATMENT FOR ADVANCED NON-SMALL CELL LUNG CANCER (NSCLC)
Approval based on superior survival outcomes of Libtayo plus chemotherapy, compared to chemotherapy alone, in a patient population with a wide range of disease characteristics
Second advanced NSCLC indication expands patient population eligible for a Libtayo-based regimen to include combination treatment with chemotherapy irrespective of PD-L1 expression levels
TARRYTOWN, N.Y., Nov. 8, 2022 /PRNewswire/ -- Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today announced that the U.S. Food and Drug Administration (FDA) has approved the PD-1 inhibitor Libtayo® (cemiplimab-rwlc) in combination with platinum-based chemotherapy for the first-line treatment of adult patients with advanced non-small cell lung cancer (NSCLC) with no EGFR, ALK or ROS1 aberrations. Patients must either have metastatic or locally advanced tumors that are not candidates for surgical resection or definitive chemoradiation. Patients may be treated with this combination irrespective of PD-L1 expression or histology.
"This second FDA approval for cemiplimab-rwlc in advanced non-small cell lung cancer greatly broadens the scope in which a cemiplimab-rwlc-based regimen can be prescribed to encompass a wide range of patients, either as single agent in those with PD-L1 ≥50% or now in combination with chemotherapy irrespective of PD-L1 expression or tumor histology," said David R. Gandara, M.D., Professor Emeritus and Senior Advisor of the Thoracic Oncology Program at the University of California Davis Comprehensive Cancer Center. "The approval is based on a Phase 3 trial designed to closely resemble a patient population with varied disease presentations that physicians manage in everyday clinical practice. Even with these diverse disease presentations, cemiplimab-rwlc combined with chemotherapy demonstrated a marked increase in overall survival, at a median of 22 months versus 13 months with chemotherapy alone. Clearly, this is an advance which is clinically meaningful for our patients with advanced stage non-small cell lung cancer."
The FDA approval is based on data from the global Phase 3 trial, EMPOWER-Lung 3, that investigated Libtayo in combination with a physician's choice of platinum-doublet chemotherapy (Libtayo combination), compared to platinum-doublet chemotherapy alone. The trial enrolled 466 patients with locally advanced or metastatic NSCLC, irrespective of PD-L1 expression or tumor histology, and with no ALK, EGFR or ROS1 aberrations. Among those enrolled, 43% had tumors with squamous histology, 67% had tumors with <50% PD-L1 expression, 15% had inoperable locally advanced disease not eligible for definitive chemoradiation, and 7% had pretreated and clinically stable brain metastases.
"Libtayo is now approved for extending the survival of patients with advanced non-small cell lung cancer as both a monotherapy in high PD-L1 expressors and in combination with chemotherapy irrespective of PD-L1 expression levels, achieving a high bar that has only been met by one other PD-1 targeting agent," said Israel Lowy, M.D., Ph.D., Senior Vice President, Translational and Clinical Sciences, Oncology at Regeneron. "With this FDA approval, Libtayo can expand its role as a key treatment option for advanced non-small lung cancer, in addition to serving as a standard-of-care for two advanced non-melanoma skin cancers. We are committed to investigating Libtayo through ongoing trials as a monotherapy and as a backbone of combination treatments in multiple cancers. We thank the many investigators, patients and their families who have participated in our pivotal trials."
Efficacy in EMPOWER-Lung 3 was assessed in 466 patients who were randomized 2:1 to receive either Libtayo 350 mg (n=312) or placebo (n=154) intravenously every 3 weeks, plus histology-specific platinum-doublet chemotherapy. The trial was stopped early based on a recommendation by the Independent Data Monitoring Committee after the Libtayo combination demonstrated a significant improvement in overall survival (OS), the primary endpoint. Efficacy results comparing the Libtayo combination to chemotherapy alone showed a:
- 22-month median OS versus 13 months, representing a 29% relative reduction in the risk of death (hazard ratio [HR]: 0.71; 95% confidence interval [CI]: 0.53 to 0.93; p=0.014). The 12-month probability of survival was 66% for the Libtayo combination versus 56% for chemotherapy, per Kaplan-Meier estimates.
- 8-month median PFS versus 5 months, representing a 44% reduction in the risk of disease progression (HR: 0.56; 95% CI: 0.44 to 0.70; p<0.0001). The 12-month probability of PFS for the Libtayo combination was 38% versus 16% for chemotherapy.
- 43% overall response rate versus 23%.
- 16-month median DOR (range: 2 to 19+) versus 7 months (range: 2 to 19+).
Safety was assessed in 312 patients in the Libtayo combination group (median duration of exposure: 38 weeks) and 153 patients in the chemotherapy group (median duration of exposure: 21 weeks). The most common adverse reactions occurring in >15% of patients were alopecia (37% Libtayo combination, 43% placebo), musculoskeletal pain (30% Libtayo combination, 36% placebo), nausea (25% Libtayo combination, 16% placebo), fatigue (23% Libtayo combination, 18% placebo), peripheral neuropathy (23% Libtayo combination, 19% placebo) and decreased appetite (17% Libtayo combination, 12% placebo). Serious adverse reactions occurred in 25% of patients, with treatment discontinuations due to adverse reactions in 5% and fatal adverse reactions in 6%. No new Libtayo safety signals were observed.
"The approval of Libtayo in the combination setting builds on the monotherapy indication in advanced non-small cell lung cancer and furthers our excitement for what's to come as we continue our potentially transformative oncology research," said George D. Yancopoulos, M.D., Ph.D., President and Chief Scientific Officer at Regeneron. "Libtayo is the backbone of our oncology strategy, designed to synergistically combine multiple modalities to provide more options for more patients. We look forward to delivering on the promise of our research in other meaningful combinations that leverage Libtayo and our homegrown pipeline of investigational bispecific antibodies."
"We welcome this latest approval for Libtayo as a first-line combination treatment for appropriate patients with advanced lung cancer," said Andrea Ferris, President and CEO at the LUNGevity Foundation. "Lung cancer remains one of the most common cancers worldwide, and every new treatment option is an important step forward against this deadly cancer."
About Libtayo
Libtayo is a fully human monoclonal antibody targeting the immune checkpoint receptor PD-1 on T-cells and was invented using Regeneron's proprietary VelocImmune® technology. By binding to PD-1, Libtayo has been shown to block cancer cells from using the PD-1 pathway to suppress T-cell activation. In the U.S. and other countries Libtayo is indicated in certain patients with advanced basal cell carcinoma (BCC), advanced cutaneous squamous cell carcinoma (CSCC) and advanced NSCLC, as well as in advanced cervical cancer in Canada and Brazil. As of July 1, 2022, Libayo is developed and marketed globally by Regeneron.
In the U.S., the generic name for Libtayo in its approved indications is cemiplimab-rwlc, with rwlc as the suffix designated in accordance with Nonproprietary Naming of Biological Products Guidance for Industry issued by the FDA. Outside of the U.S., the generic name of Libtayo in its approved indication is cemiplimab.
The extensive clinical program for Libtayo is focused on difficult-to-treat cancers. Libtayo is currently being investigated in trials as a monotherapy, as well as in combination with either conventional or novel therapeutic approaches for other solid tumors and blood cancers. These potential uses are investigational, and their safety and efficacy have not been evaluated by any regulatory authority.
U.S. FDA-approved Indications
Libtayo is a prescription medicine used to treat:
- People with a type of skin cancer called advanced cutaneous squamous cell carcinoma (CSCC) that has spread or cannot be cured by surgery or radiation.
- People with a type of skin cancer called basal cell carcinoma (BCC):
- That cannot be removed by surgery (locally advanced BCC) and have received treatment with a hedgehog pathway inhibitor (HHI), or cannot receive treatment with an HHI.
- That has spread (metastatic BCC) and have received treatment with an HHI, or cannot receive treatment with an HHI. This use is approved based on how many patients responded to treatment and how long they responded. Studies are ongoing to provide additional information about clinical benefit.
- Adults with a type of lung cancer called NSCLC:
- Libtayo may be used in combination with chemotherapy that contains a platinum medicine as your first treatment when your lung cancer has not spread outside your chest (locally advanced lung cancer) and you cannot have surgery or chemotherapy with radiation, OR your lung cancer has spread to other areas of your body (metastatic lung cancer), AND your tumor does not have an abnormal "EGFR", "ALK" or "ROS1" gene.
- Libtayo may be used alone as your first treatment when your lung cancer has not spread outside your chest (locally advanced lung cancer) and you cannot have surgery or chemotherapy with radiation, OR your lung cancer has spread to other areas of your body (metastatic lung cancer), AND your tumor tests positive for high "PD-L1", AND your tumor does not have an abnormal "EGFR", "ALK "or "ROS1" gene.
It is not known if Libtayo is safe and effective in children.
Please see full Prescribing Information, including Medication Guide.
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® (dupilumab), Libtayo, Praluent® (alirocumab), Kevzara® (sarilumab), Evkeeza® (evinacumab-dgnb) and Inmazeb™ (atoltivimab, maftivimab and odesivimab-ebgn).
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.
Cision View original content:https://www.prnewswire.com/news-releases/libtayo-cemiplimab-rwlc-in-combination-with-chemotherapy-approved-by-the-fda-as-first-line-treatment-for-advanced-non-small-cell-lung-cancer-nsclc-301672231.html
SOURCE Regeneron Pharmaceuticals, Inc.
Regeneron's Libtayo approved as first-line advanced NSCLC treatment with chemotherapy
Nov. 08, 2022 5:52 PM ET
Regeneron Pharmaceuticals, Inc. (REGN)
By: Jonathan Block, SA News Editor
- The US FDA has approved an additional indication for Regeneron Pharmaceuticals' (NASDAQ:REGN) Libtayo, this time as a first-line treatment in advanced non-small cell lung cancer (NSCLC) in combination with platinum-based chemotherapy.
- https://seekingalpha.com/news/3904187-regeneron-libtayo-approved-as-first-line-advanced-nsclc-treatment-with-chemotherapy
- https://seekingalpha.com/symbol/REGN
- https://www.libtayo.com/
- https://www.regeneron.com/
JARDIANCE® (empagliflozin tablets)
Imfinzi(durvalumab) and Imjudo(tremelimumab) with chemotherapy
Imjudo (tremelimumab) in combination with Imfinzi (durvalumab)
Landmark EMPA-KIDNEY trial showed significant benefit of Jardiance® in reducing kidney disease progression or cardiovascular death by 28% vs. placebo in people with chronic kidney disease
November 4, 2022
- EMPA-KIDNEY, the largest and broadest dedicated SGLT2 inhibitor trial in chronic kidney disease, provides new evidence for patients commonly seen in clinical practice
- Phase III trial also demonstrated a statistically significant reduction (14%) in hospitalization for any cause, bringing potential relief for patients and reducing burden on healthcare systems
OXFORD, United Kingdom and INGELHEIM, Germany and RIDGEFIELD, Conn. and INDIANAPOLIS, Nov. 4, 2022 /PRNewswire/ -- EMPA-KIDNEY phase III clinical trial met its primary endpoint by demonstrating a significant kidney and cardiovascular benefit for adults living with chronic kidney disease (CKD). When treated with Jardiance® (empagliflozin), the risk of kidney disease progression or cardiovascular death was significantly reduced by 28% vs. placebo (HR; 0.72; 95% CI 0.64 to 0.82; P<0.0001). The results were announced today during the American Society of Nephrology (ASN)'s Kidney Week 2022 by the Medical Research Council Population Health Research Unit (MRC PHRU) at the University of Oxford, which designed, conducted and analyzed EMPA-KIDNEY in a scientific collaboration with Boehringer Ingelheim and Eli Lilly and Company (NYSE: LLY). The results were also published simultaneously in The New England Journal of Medicine.
EMPA-KIDNEY is the first SGLT2 inhibitor CKD trial to demonstrate a significant reduction in all-cause hospitalizations (14%) (HR; 0.86; 95% CI 0.78 to 0.95; p=0.0025) vs. placebo, one of the pre-specified key secondary confirmatory endpoints. CKD doubles a person's risk for hospitalization and is a leading cause of death globally. Hospitalizations account for 35%-55% of total healthcare costs for people with CKD in the U.S.
The overall safety data was generally consistent with previous findings, confirming the well-established safety profile of Jardiance.
"We know that there is an urgent need for new therapies proven to delay CKD progression which can lead to the need for dialysis or transplantation. Today's results demonstrate that Jardiance may benefit adults at risk of progression, including those with or without diabetes, and across a wide range of kidney function," said William Herrington, associate professor at MRC PHRU (part of Oxford Population Health), and honorary consultant nephrologist, and EMPA-KIDNEY co-principal investigator. "By reducing the risk of kidney disease progression or cardiovascular death, Jardiance has the potential to positively impact healthcare systems worldwide."
"The design of the EMPA-KIDNEY trial included a wider range of patients than ever before," said Professor Richard Haynes, co-principal investigator. "Previous SGLT2 inhibitor trials focused on certain groups of people living with CKD, such as those with diabetes or high levels of protein in their urine. Today's positive trial results across a broad CKD population reflect an opportunity to improve the treatment of this disease and prevent people from needing dialysis."
EMPA-KIDNEY is the largest and broadest dedicated SGLT2 inhibitor trial to date. It included 6,609 participants across a wide range of underlying causes, many with co-morbidities across the spectrum of cardiovascular, kidney or metabolic conditions. The trial assessed both kidney and cardiovascular outcomes in people across the spectrum of CKD severity.
"The Boehringer Ingelheim and Lilly Alliance is incredibly proud that EMPA-KIDNEY has provided another pivotal moment for Jardiance," said Carinne Brouillon, head of Human Pharma and member of the Board of Managing Directors, Boehringer Ingelheim. "Today's data adds to the body of evidence from our clinical program which includes more than 700,000 adults with cardiovascular, kidney and metabolic conditions. EMPA-KIDNEY reinforces the potential role of Jardiance in changing the way these interconnected conditions may be managed."
Reductions in other key secondary endpoints of hospitalization for heart failure or cardiovascular death or all-cause death were not statistically significant, however the power to detect this was limited by the number of events observed. Reduction in the risk of these endpoints is consistent with the totality of the evidence from other trials which have shown statistical significance of these outcomes.
"Today's EMPA-KIDNEY trial results will be welcomed by people living with CKD and the medical community. We are also encouraged by the risk reduction for hospitalization after just two years, as this finding is in line with the significant reductions seen in prior Jardiance cardiovascular outcomes trials," said Jeff Emmick, M.D., Ph.D., vice president, Product Development, Lilly. "The Alliance looks forward to discussing plans for marketing authorization for CKD with regulators worldwide in due course."
Notes to editors
Kidney disease progression: Defined as end-stage kidney disease (the initiation of maintenance dialysis or receipt of a kidney transplant), a sustained decline in estimated glomerular filtration rate (eGFR) to below 10 mL/min/1.73 m2, kidney death or a sustained decline of at least 40% in eGFR from randomization).
End stage kidney disease: Includes initiation of maintenance dialysis or receipt of a kidney transplant
About EMPA-KIDNEY: The study of heart and kidney protection with Jardiance
EMPA-KIDNEY (NCT03594110) is a multinational, randomized, double-blind, placebo-controlled clinical trial, designed to evaluate the effect of Jardiance on kidney disease progression and cardiovascular mortality risk. The primary outcome is defined as time to a first event of either cardiovascular death or kidney disease progression, defined as end-stage kidney disease (the need for kidney replacement therapy such as dialysis or kidney transplantation), a sustained decline in eGFR to <10 mL/min/1.73 m2, kidney death, or a sustained decline of ≥40 percent in eGFR from randomization. Key secondary outcomes include cardiovascular death or hospitalization for heart failure, all-cause hospitalization and all-cause mortality. EMPA-KIDNEY includes 6,609 adults randomized from eight countries with established CKD both with and without diabetes, as well as with and without albuminuria, receiving either Jardiance 10 mg or placebo, on top of current standard of care.
About the EMPOWER program
The Boehringer Ingelheim and Lilly Alliance has developed the EMPOWER program to explore the impact of Jardiance on major clinical cardiovascular and kidney outcomes in a spectrum of cardio-kidney-metabolic conditions. Cardio-renal-metabolic conditions are the leading cause of mortality worldwide and account for up to 20 million deaths annually. Through the EMPOWER program, Boehringer Ingelheim and Lilly are working to advance knowledge of these interconnected systems and create care which offers integrated, multi-organ benefits. Comprised of nine clinical trials and two real-world evidence studies, EMPOWER reinforces the long-term commitment of the Alliance to improve outcomes for people living with cardio-kidney-metabolic conditions. With more than 700,000 adults enrolled worldwide in clinical trials, it is the broadest and most comprehensive clinical program for an SGLT2 inhibitor to date.
What is JARDIANCE?
JARDIANCE is a prescription medicine used to:
- reduce the risk of cardiovascular death and hospitalization for heart failure in adults with heart failure, when the heart cannot pump enough blood to the rest of your body
- reduce the risk of cardiovascular death in adults with type 2 diabetes who also have known cardiovascular disease
- lower blood sugar along with diet and exercise in adults with type 2 diabetes
JARDIANCE is not for people with type 1 diabetes. It may increase their risk of diabetic ketoacidosis (increased ketones in the blood or urine).
JARDIANCE is not for use to lower blood sugar in adults with type 2 diabetes who have severe kidney problems, because it may not work.
IMPORTANT SAFETY INFORMATION
Do not take JARDIANCE if you are allergic to empagliflozin or any of the ingredients in JARDIANCE.
Do not take JARDIANCE if you are on dialysis.
For more information, please see Prescribing Information and Medication Guide.
Boehringer Ingelheim and Eli Lilly and Company
In January 2011, Boehringer Ingelheim and Eli Lilly and Company announced an Alliance that centers on compounds representing several of the largest diabetes treatment classes. Depending on geographies, the companies either co-promote or separately promote the respective molecules each contributing to the Alliance. The Alliance leverages the strengths of two of the world's leading pharmaceutical companies to focus on patient needs. By joining forces, the companies demonstrate their commitment, not only to the care of people with diabetes, but also to investigating the potential to address areas of unmet medical need.
About Boehringer Ingelheim
Boehringer Ingelheim is working on breakthrough therapies that improve the lives of humans and animals. As a leading research-driven biopharmaceutical company, the company creates value through innovation in areas of high unmet medical need. Founded in 1885 and family-owned ever since, Boehringer Ingelheim takes a long-term perspective. Around 52,000 employees serve more than 130 markets in the three business areas, Human Pharma, Animal Health, and Biopharmaceutical Contract Manufacturing. Learn more at www.boehringer-ingelheim.us
About Eli Lilly and Company
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 about Lilly, please visit us at lilly.com and lilly.com/newsroom or follow us on Facebook, Instagram, Twitter and LinkedIn.
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SOURCE Eli Lilly and Company
Eli Lilly heart disease therapy meets main goal in Phase 3 kidney disease trial
Nov. 04, 2022 1:26 PM ET
By: Dulan Lokuwithana, SA News Editor1 Comment
Jardiance, a cardiovascular therapy developed by Eli Lilly (NYSE:LLY) in partnership with German pharma company Boehringer Ingelheim has met the main goal in a late-stage trial for adults with chronic kidney disease (CKD), according to data presented on Friday.
Imjudo (tremelimumab) in combination with Imfinzi (durvalumab)
Imjudo (tremelimumab) in combination with Imfinzi (durvalumab)
Imjudo (tremelimumab) in combination with Imfinzi (durvalumab)
Imjudo (tremelimumab) in combination with Imfinzi approved in the US for patients with unresectable liver cancer
PUBLISHED24 October 2022 24 October 2022 07:00 BST
Approval based on HIMALAYA Phase III trial results which showed single priming dose of Imjudo added to Imfinzi reduced risk of death by 22% vs. sorafenib
AstraZeneca’s Imjudo (tremelimumab) in combination with Imfinzi (durvalumab) has been approved in the US for the treatment of adult patients with unresectable hepatocellular carcinoma (HCC), the most common type of liver cancer. The novel dose and schedule of the combination, which includes a single dose of the anti-CTLA-4 antibody Imjudo 300mg added to the anti-PD-L1 antibody Imfinzi 1500mg followed by Imfinzi every four weeks, is called the STRIDE regimen (Single Tremelimumab Regular Interval Durvalumab).
The approval by the US Food and Drug Administration (FDA) was based on positive results from the HIMALAYA Phase III trial. In this trial, patients treated with the combination of Imjudo and Imfinzi experienced a 22% reduction in the risk of death versus sorafenib (based on a hazard ratio [HR] of 0.78, 95% confidence interval [CI] 0.66-0.92 p=0.0035).1 Results were also published in the New England Journal of Medicine Evidence showing that an estimated 31% of patients treated with the combination were still alive after three years, with 20% of patients treated with sorafenib still alive at the same duration of follow-up.2
Liver cancer is the third-leading cause of cancer death and the sixth most commonly diagnosed cancer worldwide.3,4 It is the fastest rising cause of cancer-related deaths in the US, with approximately 36,000 new diagnoses each year.5,6
Ghassan Abou-Alfa, MD, MBA, Attending Physician at Memorial Sloan Kettering Cancer Center (MSK), and principal investigator in the HIMALAYA Phase III trial, said: “Patients with unresectable liver cancer are in need of well-tolerated treatments that can meaningfully extend overall survival. In addition to this regimen demonstrating a favourable three-year survival rate in the HIMALAYA trial, safety data showed no increase in severe liver toxicity or bleeding risk for the combination, important factors for patients with liver cancer who also have advanced liver disease.”
Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: “With this first regulatory approval for Imjudo, patients with unresectable liver cancer in the US now have an approved dual immunotherapy treatment regimen that harnesses the potential of CTLA-4 inhibition in a unique combination with a PD-L1 inhibitor to enhance the immune response against their cancer.”
Andrea Wilson Woods, President & Founder, Blue Faery: The Adrienne Wilson Liver Cancer Foundation, said: “In the past, patients living with liver cancer had few treatment options and faced poor prognoses. With today's approval, we are grateful and optimistic for new, innovative, therapeutic options. These new treatments can improve long-term survival for those living with unresectable hepatocellular carcinoma, the most common form of liver cancer. We appreciate the patients, their families, and the broader liver cancer community who continue to fight for new treatments and advocate for others.”
The safety profiles of the combination of Imjudo added to Imfinzi and for Imfinzi alone were consistent with the known profiles of each medicine, and no new safety signals were identified.
Regulatory applications for Imjudo in combination with Imfinzi are currently under review in Europe, Japan and several other countries for the treatment of patients with advanced liver cancer based on the HIMALAYA results.
HIMALAYA
HIMALAYA was a randomised, open-label, multicentre, global Phase III trial of Imfinzi monotherapy and a regimen comprising a single priming dose of Imjudo 300mg added to Imfinzi 1500mg followed by Imfinzi every four weeks versus sorafenib, a standard-of-care multi-kinase inhibitor.
The trial included a total of 1,324 patients with unresectable, advanced HCC who had not been treated with prior systemic therapy and were not eligible for locoregional therapy (treatment localised to the liver and surrounding tissue).
The trial was conducted in 181 centres across 16 countries, including in the US, Canada, Europe, South America and Asia. The primary endpoint was overall survival (OS) for the combination versus sorafenib and key secondary endpoints included OS for Imfinzi versus sorafenib, objective response rate and progression-free survival (PFS) for the combination and for Imfinzi alone.
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 was recently approved to treat patients with advanced biliary tract cancer in the US based on results from the TOPAZ-1 Phase III trial. It 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 gastrointestinal (GI) cancers, ovarian cancer, endometrial cancer, and other solid tumours.
Imfinzi combinations have also demonstrated clinical benefit in metastatic NSCLC in the POSEIDON Phase III trial.
Imjudo
Imjudo (tremelimumab) is a human monoclonal antibody that targets the activity of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). Imjudo blocks the activity of CTLA-4, contributing to T-cell activation, priming the immune response to cancer and fostering cancer cell death.
Beyond HIMALAYA, Imjudo is being tested in combination with Imfinzi across multiple tumour types including locoregional HCC (EMERALD-3), SCLC (ADRIATIC) and bladder cancer (VOLGA and NILE).
Imjudo is also under review by global regulatory authorities in combination with Imfinzi and chemotherapy in 1st-line metastatic NSCLC based on the results of the POSEIDON Phase III trial, which showed the addition of a short course of Imjudo to Imfinzi plus chemotherapy improved both overall and progression-free survival compared to chemotherapy alone.
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 Imjudo (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 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.
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's Imjudo/Imfinzi combo for liver cancer gets FDA approval
Oct. 24, 2022 4:26 AM ET
By: Ravikash, SA News Editor
- The U.S. Food and Drug Administration (FDA) approved AstraZeneca's (NASDAQ:AZN) Imjudo in combination with Imfinzi to treat adult patients with unresectable hepatocellular carcinoma (HCC), a type of liver cancer.
- https://seekingalpha.com/news/3893960-astrazeneca-imjudoimfinzi-combo-for-liver-cancer-gets-fda-approval
- https://seekingalpha.com/symbol/AZN
- https://www.imfinzi.com/
- https://www.astrazeneca.com/
Opdivo (nivolumab)
Imjudo (tremelimumab) in combination with Imfinzi (durvalumab)
YESCARTA® (axicabtagene ciloleucel) suspension
Bristol Myers Squibb Presents Data from CheckMate -76K Showing Opdivo (nivolumab) Reduced the Risk of Recurrence or Death by 58% Versus Placebo in Patients with Completely Resected Stage IIB or IIC Melanoma
10/19/2022
CATEGORY:
Results from CheckMate -76K Demonstrate Statistically Significant and Clinically Meaningful Improvement in Recurrence-Free Survival
Data reinforce the benefits of Opdivo in earlier stages of melanoma
PRINCETON, N.J.--(BUSINESS WIRE)-- Bristol Myers Squibb (NYSE: BMY) today announced results from the Phase 3 CheckMate -76K trial, in which Opdivo (nivolumab) as an adjuvant therapy demonstrated a statistically significant and clinically meaningful benefit in recurrence-free survival (RFS) versus placebo in patients with completely resected stage IIB or IIC melanoma. At a pre-specified interim analysis, the trial met its primary endpoint of recurrence-free survival (RFS); Opdivo reduced the risk of recurrence or death by 58% versus placebo (hazard ratio [HR] 0.42; 95% CI 0.30-0.59; p < 0.0001). Twelve-month RFS rates for Opdivo were 89% (95% CI: 86-92) versus 79% (95% CI: 74-84) for placebo. The RFS benefit was observed across predefined subgroups in the trial, including T category and disease stage. These results are being presented as late-breaking data at the 2022 Society for Melanoma Research (SMR) Annual Meeting taking place October 17-20, 2022, during a plenary session on October 19 in Edinburgh, Scotland.
Twelve-month RFS rates by stage for patients who received Opdivo were 93% in stage IIB (versus 84% in placebo) and 84% in stage IIC (versus 72% with placebo).
The safety profile of Opdivo was consistent with that seen in previously reported studies and no new safety signals were observed at the time of the analysis. Grade 3/4 treatment-related adverse events (TRAEs) were 10% in the Opdivo arm and 2% in the placebo arm. TRAE-related discontinuation was 15% for those in the Opdivo arm and 3% for those in the placebo arm.
“Within five years after surgery, one third of stage IIB and one half of IIC patients see their cancer return. Helping reduce that risk remains a need to be addressed when it comes to treating melanoma,” said Professor Georgina Long, AO, MD, PhD, Co-Medical Director of Melanoma Institute Australia (MIA) and chair of melanoma medical oncology and translational research at MIA, The University of Sydney, and Royal North Shore and Mater Hospitals. “The data from CheckMate -76K show that treating with nivolumab in the adjuvant setting for stage IIB and IIC melanoma patients has yielded significant recurrence-free survival benefits and could be an important treatment option for this patient population.”
CheckMate -76K is part of Bristol Myers Squibb’s development program studying Opdivo and Opdivo-based combinations in earlier stages of cancer. The program currently spans seven different tumor types.
“These data add to our growing body of evidence supporting the clinical benefit of Opdivo for the treatment of melanoma, from the metastatic setting to earlier stages of cancer,” said Gina Fusaro, PhD, development program lead, melanoma, Bristol Myers Squibb. “We are continually seeking to advance our science to develop medicines that can help improve outcomes for people living with cancer.”
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 790 patients with completely resected stage IIB or IIC 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.
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.
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.
Please see US Full Prescribing Information for OPDIVO and YERVOY.
About the Bristol Myers Squibb and Ono Pharmaceutical Collaboration
In 2011, through a collaboration agreement with Ono Pharmaceutical Co., Bristol Myers Squibb expanded its territorial rights to develop and commercialize Opdivo globally, except in Japan, South Korea and Taiwan, where Ono had retained all rights to the compound at the time. On July 23, 2014, Ono and Bristol Myers Squibb further expanded the companies’ strategic collaboration agreement to jointly develop and commercialize multiple immunotherapies – as single agents and combination regimens – for patients with cancer in Japan, South Korea and Taiwan.
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 cancer drug reduces risk of death in resected stage II melanoma
Oct. 19, 2022 5:36 PM ET
Bristol-Myers Squibb Company (BMY)
By: Anuron Mitra, SA News Editor4 Comments
- Bristol-Myers Squibb (NYSE:BMY) on Wednesday said a phase 3 trial showed that its cancer drug Opdivo reduced the risk of death by 58% as an adjuvant therapy in patients with completely resected stage two melanoma, the most serious type of skin cancer.
- https://seekingalpha.com/news/3892931-bristol-myers-opdivo-cancer-drug-reduces-risk-of-death-in-resected-stage-ii-melanoma
- https://seekingalpha.com/symbol/BMY
- https://www.opdivo.com/
- https://www.bms.com/
YESCARTA® (axicabtagene ciloleucel) suspension
Imjudo (tremelimumab) in combination with Imfinzi (durvalumab)
YESCARTA® (axicabtagene ciloleucel) suspension
October 17, 2022
Kite’s Yescarta First CAR T-cell Therapy to Receive European Marketing Authorization for Use in Second-Line Diffuse Large B-cell Lymphoma and High-grade B-cell Lymphoma
-- First Treatment in 30 Years to Improve Upon Standard of Care (SOC) for Second-Line Treatment of DLBCL –
- - Based on Landmark ZUMA-7 Study, Patients with DLBCL Treated Second-Line with Yescarta Had Event-Free Survival of 8.3 Months versus Two Months for SOC [4-fold greater improvement] --
-- In ZUMA-7, Yescarta Patients with DLBCL were 2.5 Times More Likely than SOC to be Alive at Two Years Without Cancer Progression or Need for Additional Treatments --
SANTA MONICA, Calif.--(BUSINESS WIRE)-- Kite, a Gilead Company (Nasdaq: GILD), today announces that the European Commission (EC) has granted approval for the use of Yescarta® (axicabtagene ciloleucel) for the treatment of adult patients with diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma (HGBL) who relapse within 12 months from completion of, or are refractory to, first-line chemoimmunotherapy. The approval is based on results from the pivotal Phase 3 ZUMA-7 study, the largest and longest trial of a CAR T-cell therapy versus SOC in this patient population. Yescarta is now the first Chimeric Antigen Receptor (CAR) T-cell therapy approved for patients in Europe who do not respond to first-line treatment. This provides an important additional treatment option for the most common form of non-Hodgkin lymphoma. Although 60% of newly diagnosed LBCL patients, including those with DLBCL, will respond to their initial treatment, 40% will relapse or will not respond and need second-line treatment.
“We are very proud to announce Kite’s fifth approved indication in Europe in our continued commitment to the research and delivery of cell therapies with curative potential to patients who might benefit around the world,” said Christi Shaw, CEO, Kite. “Today’s approval marks an important step by providing patients in Europe this option of CAR T-cell therapy earlier in their treatment journey.”
SOC therapy for this patient population has historically been a multi-step process expected to end with a stem cell transplant. The process starts with chemoimmunotherapy, and if a patient responds to and can tolerate further treatment, they move on to high-dose chemotherapy (HDT) followed by a stem cell transplant (ASCT).
“This approval marks a major shift in the treatment of LBCL when initial treatment has failed. In ZUMA-7, treatment with axicabtagene ciloleucel resulted in an overall better outcome for patients than standard of care, especially in terms of event-free survival, marking a new era for treatment earlier in the disease pathway for more patients,” said Professor John Gribben, Professor of Medical Oncology at the Cancer Research UK Barts Centre, London. “The ZUMA-7 data has also broadened our understanding of this CAR T-cell therapy, allowing us to better manage or prevent side-effects, which is important as it moves earlier in the treatment pathway and for older patients and those with medical conditions for whom the standard of care might have been difficult.”
The ZUMA-7 study 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 vs 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 (HR: 0.28 [95% CI: 0.14-0.59]), and double-expressor lymphoma patients (HR: 0.42 [95% CI: 0.27-0.67]).
In the ZUMA-7 trial, Yescarta had a 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 Grade ≥3 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). Key secondary endpoints include objective response rate (ORR) and overall survival (OS). Additional secondary endpoints include patient reported outcomes and safety.
In the analysis of patient reported outcomes (PROs), 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.
About Yescarta
Yescarta was first approved in Europe in 2018 and is currently indicated for five types of blood cancer: Diffuse Large B-Cell Lymphoma (DLBCL); Large B-Cell Lymphoma (LBCL); High-Grade B-Cell Lymphoma (HGBL); 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 response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in 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.
Gilead's CAR-T therapy Yescarta gets European approval for second-line treatment of lymphoma
Oct. 17, 2022 5:29 PM ET
By: Dania Nadeem, SA News Editor
- Gilead's (NASDAQ:GILD) firm Kite said on Monday the European Commission had approved its (CAR) T-cell therapy, Yescarta, to treat adult patients with diffuse large B-cell lymphoma and high-grade B-cell lymphoma, who relapsed within 12 months from completion of first-line chemoimmunotherapy.
- https://seekingalpha.com/news/3892029-gileads-car-t-therapy-yescarta-gets-european-approval-for-second-line-treatment-of-lymphoma
- https://seekingalpha.com/symbol/GILD
- https://www.yescarta.com/
- https://www.gilead.com/
LIBTAYO® (CEMIPLIMAB)
TRODELVY® (sacituzumab govitecan-hziy)
KEYTRUDA® (pembrolizumab)
October 14, 2022 at 7:04 AM EDT
LIBTAYO® (CEMIPLIMAB) RECEIVES POSITIVE CHMP OPINION RECOMMENDING APPROVAL TO TREAT ADVANCED CERVICAL CANCER
Recommendation based on a Phase 3 Libtayo trial that was first and only to demonstrate significantly improved survival compared to chemotherapy in the second-line setting irrespective of PD-L1 expression status or tumor histology
TARRYTOWN, N.Y., Oct. 14, 2022 /PRNewswire/ -- Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today announced the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion for Libtayo® (cemiplimab) as a monotherapy for the treatment of adult patients with recurrent or metastatic cervical cancer and disease progression on or after platinum-based chemotherapy. The European Commission is expected to make a final decision on the application in the coming months.
The positive opinion is supported by results from the Phase 3 EMPOWER-Cervical 1 trial. In the trial (n=608), the primary endpoint of overall survival was met, with Libtayo reducing the risk of death by 31% (hazard ratio [HR]: 0.69; 95% confidence interval [CI]: 0.56-0.84; one-sided p<0.001) in the total population and 27% in the squamous cell carcinoma (SCC) population (HR: 0.73; 95% CI: 0.58-0.91; one-sided p=0.003), compared to an investigator's choice of chemotherapy. No new Libtayo safety signals were observed. Among adverse events (AE) in 10% or more patients in either group, Grade 3 or higher AEs that occurred more often in the Libtayo group (n=300) than chemotherapy (n=290) included urinary tract infection (5% Libtayo, 3% chemotherapy), back pain (1% Libtayo, less than 1% chemotherapy), asthenia (2% Libtayo, 1% chemotherapy), arthralgia (less than 1% Libtayo, 0% chemotherapy) and pyrexia (less than 1% Libtayo, 0% chemotherapy). Detailed data were published in the New England Journal of Medicine in February 2022.
Libtayo is currently approved in the European Union and other countries for the treatment of certain patients with advanced basal cell carcinoma (BCC), advanced cutaneous squamous cell carcinoma (CSCC) and advanced non-small cell lung cancer (NSCLC).
About the Phase 3 Trial
EMPOWER-Cervical 1 was an open-label, multi-center Phase 3 trial that investigated Libtayo monotherapy versus an investigator's choice of commonly used chemotherapy in patients with recurrent or metastatic cervical cancer who had progressed on platinum-based chemotherapy. Patients (median age: 51 years) were randomized to receive Libtayo (350 mg every three weeks) or chemotherapy (pemetrexed, vinorelbine, topotecan, irinotecan or gemcitabine). The primary endpoint for the trial was overall survival analyzed first among patients with SCC, then in the total population.
Patients were allowed to enroll regardless of PD-L1 expression status, with 78% of patients having SCC and 22% having adenocarcinoma or adenosquamous carcinoma. The trial included women from 14 countries: Australia, Belgium, Brazil, Canada, Greece, Italy, Japan, Poland, Russia, South Korea, Spain, Taiwan, the UK and the U.S.
In March 2021, the trial was stopped early based on the highly significant effect of Libtayo on overall survival among SCC patients and following a unanimous recommendation by the Independent Data Monitoring Committee.
About Cervical Cancer
Cervical cancer is the fourth leading cause of cancer death in women worldwide and is most frequently diagnosed between the ages of 35 and 44. Approximately 600,000 new cases of cervical cancer and 350,000 deaths from cervical cancer occur worldwide each year. Almost all cases are caused by human papillomavirus (HPV) infection, with approximately 80% classified as SCC (arising from cells lining the bottom of the cervix) and the remainder largely adenocarcinomas (arising from glandular cells in the upper cervix). Cervical cancer is often curable when detected early and effectively managed, but treatment options are more limited in advanced stages.
About Regeneron in Oncology
At Regeneron, we're applying more than three decades of scientific innovation with the goal of developing paradigm-changing therapies for patients with cancer. Our oncology portfolio is built around two foundational approaches – our approved PD-1 inhibitor Libtayo and investigational bispecific antibodies – which are being evaluated both as monotherapies and in combination with emerging therapeutic modalities. Together, they provide us with unique combinatorial flexibility to develop potentially synergistic treatments for a wide range of solid tumors and blood cancers.
If you are interested in learning more about our clinical trials, please contact us (clinicaltrials@regeneron.com or 844-734-6643) or visit our clinical trials website.
About Libtayo
Libtayo is a fully human monoclonal antibody targeting the immune checkpoint receptor PD-1 on T cells and was invented using Regeneron's proprietary VelocImmune® technology. By binding to PD-1, Libtayo has been shown to block cancer cells from using the PD-1 pathway to suppress T-cell activation. In the U.S. and other countries Libtayo is indicated in certain patients with advanced basal cell carcinoma (BCC), advanced cutaneous squamous cell carcinoma (CSCC) and advanced non-small cell lung cancer (NSCLC), as well as in advanced cervical cancer in Canada and Brazil. As of July 1, 2022, Libtayo is developed and marketed globally by Regeneron.
In the U.S., the generic name for Libtayo in its approved indications is cemiplimab-rwlc, with rwlc as the suffix designated in accordance with Nonproprietary Naming of Biological Products Guidance for Industry issued by the FDA. Outside of the U.S. the generic name of Libtayo in its approved indication is cemiplimab.
The extensive clinical program for Libtayo is focused on difficult-to-treat cancers. Libtayo is currently being investigated in trials as a monotherapy, as well as in combination with either conventional or novel therapeutic approaches for other solid tumors and blood cancers. These potential uses are investigational, and their safety and efficacy have not been evaluated by any regulatory authority.
U.S. FDA-approved Indications
Libtayo is a prescription medicine used to treat people with:
- A type of skin cancer called advanced CSCC that has spread or cannot be cured by surgery or radiation.
- A type of skin cancer called BCC:
- That cannot be removed by surgery (locally advanced BCC) and have received treatment with a hedgehog pathway inhibitor (HHI), or cannot receive treatment with an HHI.
- That has spread (metastatic BCC) and have received treatment with an HHI, or cannot receive treatment with an HHI. This use is approved based on how many patients responded to treatment and how long they responded. Studies are ongoing to provide additional information about clinical benefit.
- A type of lung cancer called NSCLC. Libtayo may be used as your first treatment when your lung cancer has not spread outside your chest (locally advanced lung cancer) and you cannot have surgery or chemotherapy with radiation, or your lung cancer has spread to other areas of your body (metastatic lung cancer), and your tumor tests positive for high "PD-L1" and your tumor does not have an abnormal "EGFR", "ALK "or "ROS1" gene.
It is not known if Libtayo is safe and effective in children.
Please see full Prescribing Information, including Medication Guide.
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.
View original content:https://www.prnewswire.com/news-releases/libtayo-cemiplimab-receives-positive-chmp-opinion-recommending-approval-to-treat-advanced-cervical-cancer-301649532.html
SOURCE Regeneron Pharmaceuticals, Inc.
EMA committee recommends expanded approval of Regeneron's Libtayo for cervical cancer
Oct. 14, 2022 9:07 AM ET
Regeneron Pharmaceuticals, Inc. (REGN), SNY
By: Ravikash, SA News Editor
- Regeneron Pharmaceuticals (NASDAQ:REGN) on Friday said that a panel of the European Medicines Agency (EMA) recommended the expanded approval of Libtayo (cemiplimab) as a monotherapy to treat adult patients with recurrent or metastatic cervical cancer and disease progression on or after platinum-based chemotherapy.
- In June, Sanofi (NASDAQ:SNY) said it was selling worldwide exclusive license rights to Libtayo to Regeneron for $900M upfront, plus royalties and other potential payments.
- https://seekingalpha.com/news/3891410-ema-committee-recommends-expanded-approval-of-regenerons-libtayo-for-cervical-cancer
- https://seekingalpha.com/symbol/REGN
- https://www.libtayo.com/
- https://www.regeneron.com/