biotecMAX™ 2024 Insight

IMFINZI® (durvalumab) plus chemotherapy

Imfinzi plus chemotherapy approved in the US for mismatch repair deficient advanced or recurrent endometrial cancer

PUBLISHED17 June 2024

Approval based on DUO-E trial results, which showed Imfinzi reduced the risk of disease progression or death by 58% vs. chemotherapy

AstraZeneca’s Imfinzi (durvalumab) in combination with carboplatin and paclitaxel followed by Imfinzi monotherapy has been approved in the US as treatment for adult patients with primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR).1

The approval by the Food and Drug Administration (FDA) was based on the results of a prespecified exploratory subgroup analysis by MMR status in the DUO-E Phase III trial. Results from DUO-E were published in the Journal of Clinical Oncology.

In the trial, Imfinzi plus carboplatin and paclitaxel followed by Imfinzi monotherapy (Imfinzi arm) reduced the risk of disease progression or death by 58% in patients with dMMR endometrial cancer versus chemotherapy alone (hazard ratio 0.42; 95% confidence interval 0.22-0.80).2

In the US, endometrial cancer is the fourth most common cancer in women, with more than 66,000 patients diagnosed and almost 12,000 deaths in 2022.3,4 Patients diagnosed at an early stage of disease have a five-year survival rate of approximately 80-90%, but there is a significant need for new treatment options for people with advanced disease, where the survival rate falls to less than 20%.5,6

Shannon N. Westin, Professor of Gynecologic Oncology and Reproductive Medicine at The University of Texas MD Anderson Cancer Center, and principal investigator of the trial, said, “With the incidence and mortality of endometrial cancer expected to continue to increase significantly in the coming decades, it is more important than ever that we bring new treatment options to patients at the earliest possible moment in their care. This approval underlines clear evidence that durvalumab plus chemotherapy followed by durvalumab monotherapy delivers important clinical benefits for patients with mismatch repair deficient endometrial cancer.”

Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: “There have been limited advances in the treatment of endometrial cancer in the last few decades, and continued innovation is critical as the burden of this cancer is expected to grow in the future. Immunotherapy in combination with chemotherapy is emerging as a new standard of care in this setting, and the approval of Imfinzi offers an important new option for patients with mismatch repair deficient disease.”

The safety and tolerability profile of the Imfinzi and chemotherapy regimen was generally manageable, well tolerated and broadly consistent with prior clinical trials with no new safety signals.1,2

The Lynparza (olaparib) and Imfinzi arm, which investigated Imfinzi plus chemotherapy followed by Imfinzi plus Lynparza as maintenance therapy, also met the primary endpoint of progression-free survival (PFS). The trial continues to assess OS as a key secondary endpoint for both arms. Regulatory applications for both Imfinzi as well as Imfinzi and Lynparza regimens are currently under review in the EU, Japan and several other countries based on the DUO-E results.

Notes

Endometrial cancer
Endometrial cancer is a highly heterogeneous disease that originates in the tissue lining of the uterus and is most common in women who have already been through menopause, with the average age at diagnosis being over 60 years old.7-10 It is the sixth most common cancer in women worldwide.11,12 Incidence and mortality of endometrial cancer are expected to increase by approximately 61% and 87% respectively (from 420,400 cases and 97,700 deaths in 2022 to 676,300 cases and 183,100 deaths) in 2050.13

The majority of patients with endometrial cancer are diagnosed at an early stage of disease, where the cancer is confined to the uterus.9,10 They are typically treated with surgery and/or radiation, and the five-year survival rate is high (approximately 80-90%).5,6 Patients with advanced disease (Stage III-IV) usually have a much poorer prognosis, with the five-year survival rate falling to less than 20%.5,6 Immunotherapy combined with chemotherapy is emerging as a new standard of care for advanced endometrial cancer, particularly for patients with dMMR disease, who make up approximately 20-30% of all patients with this type of cancer.6,14,15,16 There remains a high unmet need for treatments for the remaining 70-80% of endometrial cancer patients with pMMR disease.15,16

DUO-E
The DUO-E trial (GOG 3041/ENGOT-EN10) is a three-arm, randomised, double-blind, placebo-controlled, multicentre Phase III trial of 1st-line Imfinzi (durvalumab) plus platinum-based chemotherapy (carboplatin and paclitaxel) followed by either Imfinzi monotherapy or Imfinzi plus Lynparza (olaparib) as maintenance therapy versus platinum-based chemotherapy alone as a treatment for patients with newly diagnosed advanced or recurrent endometrial cancer.

The DUO-E trial randomised 699 patients with newly diagnosed advanced or recurrent epithelial endometrial carcinoma to receive either Imfinzi (1120mg) or placebo, given every three weeks in addition to standard-of-care platinum-based chemotherapy. After 4-6 cycles of chemotherapy, patients (whose disease had not progressed) then received either Imfinzi (1500mg) or placebo every four weeks as maintenance, plus 300mg Lynparza (300mg BID [2x150mg tablets, twice a day]) or placebo until disease progression.

The dual primary endpoint was PFS of each treatment arm versus standard of care. Key secondary endpoints included overall survival (OS), safety and tolerability. The trial continues to assess OS for both Imfinzi monotherapy and Imfinzi plus Lynparza as maintenance therapy in the overall trial population. Mismatch repair (MMR) status, recurrence status and geographic location were stratification factors. The trial was sponsored independently by AstraZeneca and conducted in 253 study locations across 22 countries including the US, Europe, South America and Asia.

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

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 indications in unresectable, Stage III NSCLC and ES-SCLC, Imfinzi is currently approved in a number of countries in combination with a short course of tremelimumab (Imjudo) and chemotherapy for the treatment of metastatic NSCLC.

Imfinzi is also approved in a number of countries in combination with chemotherapy in locally advanced or metastatic biliary tract cancer and in combination with Imjudo in unresectable hepatocellular carcinoma (HCC). Imfinzi is also approved as a monotherapy in unresectable HCC in Japan and the EU.

Since the first approval in May 2017, more than 220,000 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, breast cancer, several gastrointestinal cancers and other solid tumours.

https://www.imfinzi.com/

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 monotherapy 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's innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on social media @AstraZeneca.

AstraZeneca PLC

AstraZeneca gets FDA okay for Imfinzi for endometrial cancer

Jun. 17, 2024 12:41 PM ET

AstraZeneca PLC (AZN) Stock

By: Val Brickates Kennedy, SA News Editor1 Comment

AstraZeneca (NASDAQ:AZN) said the FDA has approved its drug Imfinzi, also known as durvalumab, for the treatment of a certain type of endometrial cancer.

The FDA approved Imfinzi in combination with carboplatin and paclitaxel followed by Imfinzi as a monotherapy in the treatment of adults with primary advanced or recurrent endometrial cancer that is mismatch repair deficient, or dMMR.

https://seekingalpha.com/news/4116719-astrazeneca-gets-fda-okay-for-imfinzi-for-endometrial-cancer?mailingid=35745520&messageid=2900&serial=35745520.5797&source=email_2900&utm_campaign=rta-stock-news&utm_content=link-1&utm_medium=email&utm_source=seeking_alpha&utm_term=35745520.5797

AstraZeneca PLC (AZN) Stock

https://www.astrazeneca.com/

https://www.imfinzi.com/

IMFINZI and IMJUDO are prescription medications that may treat certain cancers. IMFINZI is used to treat adults with a type of lung cancer called NSCLC. IMFINZI may be used alone when your NSCLC has not spread outside your chest, cannot be removed by surgery, and has responded or stabilized with initial treatment with chemotherapy that contains platinum, given at the same time as radiation therapy. IMFINZI may be used in combination with IMJUDO and chemotherapy that contains platinum when your NSCLC has spread to other parts of your body (metastatic) and your tumor does not have an abnormal “EGFR” or “ALK” gene. IMFINZI is used to treat adults with a type of lung cancer called SCLC. IMFINZI may be used with the chemotherapy medicines etoposide and carboplatin or cisplatin as your first treatment when your SCLC has spread within your lungs or to other parts of the body (extensive-stage small cell lung cancer, or ES-SCLC). IMFINZI is used to treat adults with a type of cancer called BTC, including cancer of the bile ducts (cholangiocarcinoma) and gallbladder cancer. IMFINZI may be used in combination with chemotherapy medicines gemcitabine and cisplatin when your BTC has spread to nearby tissues (locally advanced), or has spread to other parts of the body (metastatic). IMFINZI is used in combination with IMJUDO to treat adults with a type of liver cancer that cannot be removed by surgery (unresectable hepatocellular carcinoma or uHCC). It is not known if IMFINZI and IMJUDO are safe and effective in children.

BLINCYTO® (blinatumomab)

FDA APPROVES BLINCYTO® (BLINATUMOMAB) IN CD19-POSITIVE PHILADELPHIA CHROMOSOME-NEGATIVE B-CELL PRECURSOR ACUTE LYMPHOBLASTIC LEUKEMIA (B-ALL) IN THE CONSOLIDATION PHASE

BLINCYTO® Added to Multiphase Consolidation Chemotherapy Reduced Risk of Death by 58% Showing Superior Overall Survival Versus Chemotherapy Alone

First and Only Bispecific T-cell Engager (BiTE®) Therapy for Consolidation Treatment Regardless of Measurable Residual Disease (MRD) Status

THOUSAND OAKS, Calif., June 14, 2024 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today announced the U.S. Food and Drug Administration (FDA) has approved BLINCYTO® (blinatumomab) for the treatment of adult and pediatric patients one month or older with CD19-positive Philadelphia chromosome-negative B-cell precursor acute lymphoblastic leukemia (B-ALL) in the consolidation phase, regardless of measurable residual disease (MRD) status.

"B-ALL is an aggressive blood cancer with enduring high unmet need. BLINCYTO has helped thousands of patients with B-ALL over the last 10 years. Today's approval in the frontline consolidation phase, regardless of MRD status, allows us to reach more patients than ever with this transformative, first-in-class Bispecific T-cell Engager (BiTE®) therapy," said Jay Bradner, M.D., executive vice president, Research and Development, and chief scientific officer at Amgen.

The approval marks the third indication for BLINCYTO and is based primarily on the Phase 3 E1910 clinical trial led by ECOG-ACRIN Cancer Research Group that studied patients with newly diagnosed Philadelphia chromosome-negative B-ALL receiving postinduction consolidation treatment, which aims to deepen remission to achieve durable responses. Study results demonstrated that BLINCYTO added to multiphase consolidation chemotherapy showed superior overall survival (OS) versus chemotherapy alone. The 3-year OS was 84.8% in the BLINCYTO plus chemotherapy arm (n=112) and 69% in the chemotherapy arm (n=112), with the hazard ratio for OS of 0.42. With a median follow-up of 4.5 years, the 5-year OS was 82.4% in the BLINCYTO plus chemotherapy arm and 62.5% in the chemotherapy arm.

"In the E1910 study, blinatumomab reduced risk of death and showed a remarkable improvement in overall survival," said Selina M. Luger, M.D., professor of hematology-oncology at the University of Pennsylvania's Perelman School of Medicine and Abramson Cancer Center, chair of the ECOG-ACRIN Leukemia Committee and an investigator on the study. "This approval redefines the standard of care for patients with B-ALL and provides them with a more effective treatment option than standard chemotherapy alone."

"The risk of B-ALL recurrence after the initial phase of treatment is relatively high, making this approval for patients noteworthy," said E. Anders Kolb, M.D., president and chief executive officer of The Leukemia & Lymphoma Society. "B-ALL is the most common type of ALL and having another effective option available earlier in a patient's treatment journey is critical for clinicians who are working to give these patients more time with their loved ones."

The E1910 study was designed and conducted independently from industry. ECOG-ACRIN sponsored the trial with public funding from the National Cancer Institute (NCI), part of the National Institutes of Health (NIH). Other NCI-funded network groups took part in the study. In addition, Amgen provided BLINCYTO and support through an NCI Cooperative Research and Development Agreement.

About Acute Lymphoblastic Leukemia (ALL)
ALL, also known as acute lymphoblastic leukemia, is a fast-growing type of blood cancer that develops in the bone marrow and can sometimes spread to other parts of the body, including the lymph nodes, liver, spleen, and central nervous system. ALL is a rare disease, with 6,540 new cases diagnosed in the U.S. in 2023 affecting both children and adults.1 B-ALL begins in immature cells that would normally develop into B-cell lymphocytes, which are white blood cells that grow in bone marrow.2,3 B-ALL is the most common type of ALL, constituting approximately 75% of cases in adults.4

About BLINCYTO® (blinatumomab)
BLINCYTO is the first globally approved BiTE® immuno-oncology therapy that targets CD19 surface antigens on B cells. BiTE® molecules fight cancer by helping the body's immune system detect and target malignant cells by engaging T cells (a type of white blood cell capable of killing other cells perceived as threats) to cancer cells. By bringing T cells near cancer cells, the T cells can inject toxins and trigger cancer cell death (apoptosis). BiTE® immuno-oncology therapies are currently being investigated for their potential to treat a wide variety of cancers.

BLINCYTO was granted breakthrough therapy and Priority Review designations by the U.S. FDA and is approved in the U.S. for the treatment of:

Adult and pediatric patients one month or older with CD19-positive Philadelphia chromosome-negative B-ALL during the consolidation phase of multiphase therapy.
CD19-positive B-ALL in first or second complete remission with MRD greater than or equal to 0.1% in adults and pediatric patients one month or older.
Relapsed or refractory CD19-positive B-ALL in adults and pediatric patients one month or older.

In the European Union (EU), BLINCYTO is indicated as monotherapy for the treatment of:

Adults with Philadelphia chromosome-negative CD19-positive relapsed or refractory B-ALL. Patients with Philadelphia chromosome-positive B-ALL should have failed treatment with at least two tyrosine kinase inhibitors (TKIs) and have no alternative treatment options.
Adults with Philadelphia chromosome-negative CD19-positive B-ALL in first or second complete remission with MRD greater than or equal to 0.1%.
Pediatric patients aged 1 year or older with Philadelphia chromosome-negative CD19-positive B-ALL which is refractory or in relapse after receiving at least two prior therapies or in relapse after receiving prior allogeneic hematopoietic stem cell transplantation.
Pediatric patients aged 1 year or older with high-risk first relapsed Philadelphia chromosome-negative CD19-positive B-ALL as part of the consolidation therapy.

INDICATIONS

BLINCYTO® (blinatumomab) is indicated for the treatment of CD19-positive B-cell precursor acute lymphoblastic leukemia (ALL) in adult and pediatric patients one month and older with:

Philadelphia chromosome-negative disease in the consolidation phase of multiphase chemotherapy.
Minimal residual disease (MRD) greater than or equal to 0.1% in first or second complete remission.
Relapsed or refractory disease.
https://www.blincyto.com/

BLINCYTO® IMPORTANT SAFETY INFORMATION

WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGICAL TOXICITIES including IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME

Cytokine Release Syndrome (CRS), which may be life-threatening or fatal, occurred in patients receiving BLINCYTO®. Interrupt or discontinue BLINCYTO® and treat with corticosteroids as recommended.
Neurological toxicities, including immune effector cell-associated neurotoxicity syndrome (ICANS) which may be severe, life-threatening, or fatal, occurred in patients receiving BLINCYTO®. Interrupt or discontinue BLINCYTO® as recommended.

Contraindications

BLINCYTO® is contraindicated in patients with a known hypersensitivity to blinatumomab or to any component of the product formulation.

Please see BLINCYTO® full Prescribing Information, including BOXED WARNINGS.

About BiTE® Technology
Bispecific T-cell Engager (BiTE®) technology is a targeted immuno-oncology platform that is designed to engage patient's own T cells to any tumor-specific antigen, activating the cytotoxic potential of T cells to eliminate detectable cancer. The BiTE® immuno-oncology platform has the potential to treat different tumor types through tumor-specific antigens. The BiTE® platform has a goal of leading to off-the-shelf solutions, which have the potential to make innovative T cell treatment available to all providers when their patients need it. Amgen is advancing multiple BiTE® molecules across a broad range of hematologic malignancies and solid tumors, further investigating BiTE® technology with the goal of enhancing patient experience and therapeutic potential. To learn more about BiTE® technology, visit https://www.amgenoncology.com/bite-platform.html.

About Amgen
Amgen discovers, develops, manufactures and delivers innovative medicines to help millions of patients in their fight against some of the world's toughest diseases. More than 40 years ago, Amgen helped to establish the biotechnology industry and remains on the cutting-edge of innovation, using technology and human genetic data to push beyond what's known today. Amgen is advancing a broad and deep pipeline that builds on its existing portfolio of medicines to treat cancer, heart disease, osteoporosis, inflammatory diseases and rare diseases.

In 2024, Amgen was named one of the "World's Most Innovative Companies" by Fast Company and one of "America's Best Large Employers" by Forbes, among other external recognitions. Amgen is one of the 30 companies that comprise the Dow Jones Industrial Average®, and it is also part of the Nasdaq-100 Index®, which includes the largest and most innovative non-financial companies listed on the Nasdaq Stock Market based on market capitalization.

For more information, visit Amgen.com and follow Amgen on X, LinkedIn, Instagram, TikTok, YouTube and Threads.

Amgen Logo. (PRNewsFoto/Amgen) (PRNewsFoto/)

View original content to download multimedia:https://www.prnewswire.com/news-releases/fda-approves-blincyto-blinatumomab-in-cd19-positive-philadelphia-chromosome-negative-b-cell-precursor-acute-lymphoblastic-leukemia-b-all-in-the-consolidation-phase-302173376.html

SOURCE Amgen

FDA grants expanded approval for Amgen's Blincyto in ALL

Jun. 14, 2024 5:13 PM ET

Amgen Inc. (AMGN) Stock

By: Val Brickates Kennedy, SA News Editor

The FDA has granted expanded approval for Amgen’s (NASDAQ:AMGN) Blincyto for the treatment of certain adult and pediatric patients with acute lymphoblastic leukemia, or ALL.

More specifically, the agency approved the drug for patients aged one month or older with CD19-positive Philadelphia chromosome-negative B-cell precursor acute lymphoblastic leukemia, or B-ALL, in the consolidation phase, regardless of measurable residual disease, or MRD, status.

https://seekingalpha.com/news/4116442-fda-grants-expanded-approval-for-amgens-blincyto-in-all?source=content_type%3Areact%7Cfirst_level_url%3Amarket-news%7Csection_asset%3Amain%7Csection%3Ahealthcare

Amgen Inc. (AMGN) Stock

https://www.amgen.com/

https://www.blincyto.com/

BLINCYTO® (blinatumomab) is indicated for the treatment of CD19-positive B-cell precursor acute lymphoblastic leukemia (ALL) in adult and pediatric patients one month and older with: Philadelphia chromosome-negative disease in the consolidation phase of multiphase chemotherapy. Minimal residual disease (MRD) greater than or equal to 0.1% in first or second complete remission. Relapsed or refractory disease.

ELREXFIO (elranatamab-bcmm)

ELREXFIO™ Shows Median Overall Survival of More Than Two Years in People with Relapsed or Refractory Multiple Myeloma

Friday, June 14, 2024 - 03:00am View pdf

Patients in MagnetisMM-3 demonstrated a median overall survival (OS) of 24.6 months, with median progression-free survival (PFS) of 17.2 months

NEW YORK--(BUSINESS WIRE)-- Pfizer Inc. (NYSE: PFE) today announced detailed overall survival (OS) results from the Phase 2 MagnetisMM-3 study of ELREXFIO™ (elranatamab-bcmm) in patients with heavily pretreated relapsed or refractory multiple myeloma (RRMM). The study demonstrated a median OS of 24.6 (95% CI, 13.4, NE) months in cohort A (n=123) of the pivotal single arm trial.

These data from MagnetisMM-3 will be presented during a poster session (#932) at the European Hematology Association (EHA) Hybrid Congress in Madrid, Spain, from June 13-16. Additional presentations at EHA 2024 will highlight ELREXFIO data across the comprehensive MagnetisMM clinical trial program.

“These compelling overall survival data support the clinical benefit ELREXFIO has already demonstrated and its potential to be a transformative treatment option for people with multiple myeloma,” said Roger Dansey, M.D., Chief Development Officer, Oncology, Pfizer. “The latest results from MagnetisMM-3 reinforce the very promising efficacy observed with ELREXFIO in a relapsed or refractory setting, with deep and durable responses and although definitive conclusions cannot be drawn across studies, the longest reported median progression-free survival among B-cell maturation antigen bispecific antibodies.”

After more than two years of follow-up in the MagnetisMM-3 trial, the overall response rate (ORR) for patients on ELREXFIO was 61.0% (37.4% ≥complete response rate (CRR)), with responses deepening over time, and the median duration of response (DOR) was not reached. At two years, the estimated DOR rate was 66.9% (95% CI: 54.4, 76.7) for all responders, and 87.9% (95% CI: 73.1, 94.8) for patients with CR or better response. Median progression-free survival (PFS) was 17.2 months (95% CI: 9.8 months-NE). For patients with CR or better response, the median PFS was not reached, and at two years, the estimated PFS rate was 90.6% (95% CI: 76.9, 96.4).

“People with relapsed or refractory multiple myeloma often have limited therapeutic options as their disease progresses due to treatment resistance, resulting in increasingly shorter remission and duration of response,” said MagnetisMM-3 clinical trial investigator Mohamad Mohty, M.D., Ph.D., Professor of Hematology and Head of the Hematology and Cellular Therapy Department at the Saint-Antoine Hospital and Sorbonne University, Paris, France. “These impactful overall survival data are particularly encouraging given the very advanced patient population with characteristics associated with poorer outcomes.”

The safety and tolerability of ELREXFIO in MagnetisMM-3 were consistent with what have been previously observed. Five patients (4.1%) experienced secondary primary malignancies (SPMs), all cases being squamous cell carcinoma of the skin, consistent with SPMs often observed in patients with multiple myeloma (MM), while no hematological SPMs were reported. Due to the risk of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), patients should be monitored for signs and symptoms for 48 hours after administration of each of the two step-up doses within the ELREXFIO dosing schedule and instructed to remain in proximity of a healthcare facility. In the EU, precautionary hospitalization is not required. Patients are not required to stay near a healthcare facility for the 76 mg first treatment dose.

Based on results of the MagnetisMM-3 trial, ELREXFIO received accelerated approval in August 2023 from the U.S. Food and Drug Administration for the treatment of adult patients with RRMM who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody. Continued approval for this indication is contingent upon verification of clinical benefit in a confirmatory trial. In December 2023, the European Commission granted conditional marketing authorization for ELREXFIO for the treatment of adult patients with RRMM who have received at least three prior therapies, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 antibody, and have demonstrated disease progression on the last therapy. ELREXFIO has also received approval in Switzerland, Brazil and Canada under Project Orbis, a framework for the concurrent submission and review of oncology drugs among international partners to potentially expedite approvals. Two other countries (Australia and Singapore) are participating in Project Orbis. The Medicines and Healthcare products Regulatory Agency (MHRA) granted ELREXFIO authorization for Great Britain for RRMM.

Pfizer’s comprehensive ongoing MagnetisMM clinical development program is investigating the use of elranatamab across the entire spectrum of patients with MM, from RRMM to newly diagnosed MM. Ongoing registrational-intent trials are comparing elranatamab to current standards of care both as monotherapy and in combination with standard or novel therapies. These include MagnetisMM-4 investigating elranatamab treatment with other anti-cancer therapies, MagnetisMM-5 in the double-class exposed setting, MagnetisMM-6 in newly diagnosed patients who are ineligible for stem cell transplant, MagnetisMM-7 in newly diagnosed patients after transplant, and MagnetisMM-32 in patients with prior anti-CD38-directed therapy.

About MagnetisMM-3

MagnetisMM-3 is an open-label, multicenter, non-randomized Phase 2 study of ELREXFIO monotherapy in participants with multiple myeloma who are refractory to at least one proteasome inhibitor, one immunomodulatory drug, and one anti-cluster of differentiation 38 antibody. The study enrolled two cohorts of participants: one with and one without prior treatment with a B-cell maturation antigen-directed antibody-drug conjugate or chimeric antigen receptor T-cell therapy. Participants received subcutaneous ELREXFIO as two step-up priming doses followed by a weekly 76 mg injection. The primary endpoint is objective response rate as assessed by Blinded Independent Central Review (BICR). Key secondary endpoints include duration of response, progression-free survival, minimal residual disease negativity rate, overall survival, and safety. For more information about the trial, visit www.clinicaltrials.gov (NCT04649359).

About Multiple Myeloma

Multiple myeloma (MM) is an aggressive and currently incurable blood cancer that affects plasma cells made in the bone marrow. Healthy plasma cells make antibodies that help the body fight infection.1 MM is the second most common type of blood cancer, with over 50,000 new cases diagnosed annually in Europe and over 187,000 new cases diagnosed globally each year.2,3 About 40% of those diagnosed with MM won’t survive beyond five years,4 and most will receive 4 or more lines of therapy due to relapse.5 While disease trajectory varies for each person, relapses are nearly inevitable.6 The goal of therapy for people with relapsing or refractory MM is to achieve disease control with acceptable toxicity and improved quality of life.7

About ELREXFIO (elranatamab-bcmm)

ELREXFIO is a subcutaneously delivered B-cell maturation antigen (BCMA)-cluster of differentiation (CD)3-directed bispecific antibody immunotherapy that binds to BCMA on myeloma cells and CD3 on T cells, activating the T cells to kill myeloma cells.

U.S. INDICATION

ELREXFIO may cause side effects that are serious, life-threatening, or can lead to death, including cytokine release syndrome (CRS) and neurologic problems. CRS is common during treatment with ELREXFIO.

https://www.elrexfio.com/

What is ELREXFIO?

ELREXFIO is a prescription medication used to treat adults with multiple myeloma who:

have already received at least 4 treatment regimens, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody, to treat their multiple myeloma, and
their cancer has come back or did not respond to prior treatment

ELREXFIO was approved based on patient responses and durability of response. There are ongoing studies to confirm its clinical benefit. It is not known if ELREXFIO is safe and effective in children.

Please read full Prescribing Information, including BOXED WARNING, for ELREXFIO.

About Pfizer Oncology

At Pfizer Oncology, we are at the forefront of a new era in cancer care. Our industry-leading portfolio and extensive pipeline includes three core mechanisms of action to attack cancer from multiple angles, including small molecules, antibody-drug conjugates (ADCs), and bispecific antibodies, including other immune-oncology biologics. We are focused on delivering transformative therapies in some of the world’s most common cancers, including breast cancer, genitourinary cancer, hematology-oncology, and thoracic cancers, which includes lung cancer. Driven by science, we are committed to accelerating breakthroughs to help people with cancer live better and longer lives.

About Pfizer: Breakthroughs That Change Patients’ Lives

At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products, including innovative medicines and vaccines. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world’s premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For 175 years, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on our website at www.Pfizer.com. In addition, to learn more, please visit us on www.Pfizer.com and follow us on X at @Pfizer and @Pfizer News, LinkedIn, YouTube and like us on Facebook at Facebook.com/Pfizer.

Source: Pfizer Inc.

Pfizer's Elrexfio buoyed by multiple myeloma survival data

Jun. 14, 2024 8:49 AM ET

Pfizer Inc. (PFE) Stock

By: Jonathan Block, SA News Editor

Heavily pretreated multiple myeloma patients treated with Pfizer's (NYSE:PFE) Elrexfio (elranatamab) demonstrated a median survival of 24.6 months in a phase 2 trial.
After more than two years of follow-up in the MagnetisMM-3 trial, the overall response rate for treated patients was 61.0%, with responses becoming more significant over time.
https://seekingalpha.com/news/4116165-pfizer-elrexfio-buoyed-by-multiple-myeloma-survival-data?source=content_type%3Areact%7Cfirst_level_url%3Amarket-news%7Csection_asset%3Amain%7Csection%3Ahealthcare
Pfizer Inc. (PFE) Stock
https://www.pfizer.com/
https://www.elrexfio.com/

What is ELREXFIO? ELREXFIO is a prescription medication used to treat adults with multiple myeloma who: have already received at least 4 treatment regimens, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody to treat their multiple myeloma, and their cancer has come back or did not respond to prior treatment ELREXFIO was approved based on patient responses and durability of response. There are ongoing studies to confirm its clinical benefit. It is not known if ELREXFIO is safe and effective in children.

FARXIGA® (dapagliflozin) tablets

Farxiga approved in the US
for the treatment of paediatric type-2 diabetes

PUBLISHED12 June 2024

US patients aged 10 years and older can now benefit from Farxiga for type-2 diabetes
Approval based on results from T2NOW, one of the largest paediatric type-2 diabetes
Phase III trials to date

AstraZeneca’s Farxiga (dapagliflozin) has been approved by the US Food and Drug Administration (FDA) to improve glycaemic control in paediatric patients with type-2 diabetes (T2D) aged 10 years and older.1 The FDA approval was based on positive results from the paediatric T2NOW Phase III trial.2 Farxiga was previously approved in the US in adults with T2D as an adjunct to diet and exercise to improve glycaemic control.1

Ruud Dobber, Executive Vice President, BioPharmaceuticals Business Unit, AstraZeneca, said: “The prevalence of type-2 diabetes continues to rise in children and adolescents, yet oral treatment options have remained limited for this population. Today’s approval represents an important milestone for paediatric patients living with type-2 diabetes in the US, extending this medicine’s potential benefits to even more patients facing high unmet needs and reinforcing AstraZeneca’s commitment to delivering innovative treatments across cardiovascular, renal and metabolic diseases.”

T2D is a chronic disease affecting people of all ages.3,4 The incidence and prevalence of T2D in children and adolescents are increasing globally.5 In the US, there are nearly 30,000 patients under 20 living with T2D with 5,300 new cases diagnosed each year, according to the US Centers for Disease Control and Prevention and recent research.6,7 Younger patients often experience earlier onset of complications and faster advancement of disease compared to adults with the same condition.8-15

Data from the T2NOW Phase III trial, published in The New England Journal of Medicine Evidence, demonstrated a significant reduction in A1C, a marker of average blood sugar, for patients treated with Farxiga compared to patients receiving placebo.2,16 Adjusted mean change in A1C was -0.62% for Farxiga versus +0.41% for placebo, a difference of -1.03% (95% CI: -1.57-0.49; p<0.001).2 Statistical significance was achieved in the primary endpoint and in all secondary endpoints versus placebo at week 26, demonstrating Farxiga can provide clinically meaningful improvements in glycaemia for children and adolescents with T2D.2 The safety results in this patient population were consistent with those in adults with T2D, in line with the well-characterised safety profile for Farxiga.2

Farxiga, a first-in-class, oral, once-daily sodium-glucose cotransporter 2 (SGLT2) inhibitor, was approved in 126 countries, including the EU (marketed under the brand name Forxiga), as an adjunct to diet and exercise to improve glycaemic control in adults with T2D.

Forxiga is also approved for paediatric patients aged 10 years and above with T2D in 56 countries, including the EU and other regions, based on results from the T2GO Phase III clinical trial.17,18

Additional regulatory submissions and rollout plans are under consideration pending further market evaluations.

Notes

T2D
T2D is a chronic disease characterised by pathophysiologic defects leading to elevated glucose levels, or hyperglycaemia.3 Over time, this sustained hyperglycaemia contributes to further progression of the disease.3 The prevalence of diabetes is projected to reach 783 million by 2045.3 T2D is the most common type of diabetes, accounting for over 90% of all diabetes worldwide.19 Significant unmet medical need still exists, as many patients have poor blood sugar control and low medication adherence.3,20

T2NOW
T2NOW was a randomised, double-blind, placebo-controlled Phase III trial designed to evaluate the efficacy and safety of dapagliflozin as add-on treatment in children and adolescents with T2D receiving metformin, insulin or both.2 Patients were randomised to dapagliflozin, saxagliptin or placebo.2 Those receiving an active drug were further randomised to continue their current dose, or up-titrate to a higher dose of the same active treatment.2 The primary endpoint was change in A1C after 26 weeks vs placebo for dapagliflozin (5 or 10 mg) or saxagliptin (2.5 or 5 mg).2 Secondary endpoints included change in fasting plasma glucose and proportion of patients (A1C ≥7% at baseline) achieving A1C <7.0% (53 mmol/mol) after 26 weeks.2

Farxiga
Farxiga (dapagliflozin) in the US and marketed as Forxiga in the rest of world, is a first-in-class, oral, once-daily sodium-glucose cotransporter 2 (SGLT2) inhibitor. As of June 2024, Forxiga was approved in 126 countries as an adjunct to diet and exercise to improve glycaemic control in adults with T2D. Forxiga is approved for paediatric patients aged 10 years and above with T2D in the EU and other countries based on the T2GO trial.17,18

In addition, Forxiga is approved for the treatment of heart failure across the full ventricular ejection fraction range (HFrEF and HFpEF) and CKD in adult patients in more than 100 countries around the world. Forxiga was the first heart failure medication to demonstrate mortality benefit across the full ejection fraction range.21

Research has shown Forxiga’s efficacy in preventing and delaying cardiorenal disease, while also protecting the organs – important findings given the underlying links between the heart, kidneys and pancreas.22-24 Damage to one of these organs can cause the other organs to fail, contributing to leading causes of death worldwide, including T2D, heart failure (HF) and chronic kidney disease (CKD).25-28

https://www.farxiga.com/

AstraZeneca in CVRM
Cardiovascular, Renal and Metabolism (CVRM), part of BioPharmaceuticals, forms one of AstraZeneca’s main disease areas and is a key growth driver for the Company. By following the science to understand more clearly the underlying links between the heart, kidneys, liver and pancreas, AstraZeneca is investing in a portfolio of medicines for organ protection by slowing or stopping disease progression, and ultimately paving the way towards regenerative therapies. The Company’s ambition is to improve and save the lives of millions of people, by better understanding the interconnections between CVRM diseases and targeting the mechanisms that drive them, so we can detect, diagnose and treat people earlier and more effectively.

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’s innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on social media @AstraZeneca

AstraZeneca's Farxiga approved for type 2 diabetes for children as young as 10

Jun. 12, 2024 3:30 PM ET

AstraZeneca PLC (AZN) Stock

By: Jonathan Block, SA News Editor

The U.S. FDA has expanded the indication of AstraZeneca's Farxiga (dapagliflozin) to treat type 2 diabetes in children as young as 10 years old.
The drug was already approved for this indication in adults.
https://seekingalpha.com/news/4115335-astrazeneca-farxiga-approved-type-2-diabetes-children-young-10?mailingid=35695335&messageid=2900&serial=35695335.5271&source=email_2900&utm_campaign=rta-stock-news&utm_content=link-1&utm_medium=email&utm_source=seeking_alpha&utm_term=35695335.5271
AstraZeneca PLC (AZN) Stock
https://www.astrazeneca.com/
https://www.farxiga.com/

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

Arexvy (Respiratory Syncytial Virus (RSV) Vaccine, Adjuvanted)

07 June 2024 Issued: London, UK For media and investors only

US FDA approves expanded age indication for GSK’s Arexvy, the first respiratory syncytial virus (RSV) vaccine for adults aged 50-59 at increased risk

Download (PDF, 224.9KB)

Over 13 million US adults aged 50-59 years have a medical condition that increases their risk of severe RSV outcomes1
Clinical development programme continues to evaluate safety and immunogenicity in adults 18+ with data read-outs expected H2 2024

GSK plc (LSE/NYSE: GSK) today announced that the US Food and Drug Administration (FDA) has approved Arexvy (Respiratory Syncytial Virus (RSV) Vaccine, Adjuvanted) for the prevention of RSV lower respiratory tract disease (LRTD) in adults 50 through 59 years of age who are at increased risk. In the US, the vaccine is currently approved for use in adults aged 60 and older and recommended by CDC/ACIP using shared clinical decision-making.

A systematic review of studies in the US showed that RSV is estimated to cause 42,000 hospitalisations* each year in adults aged 50-64 years old.2 Adults with underlying medical conditions, such as chronic obstructive pulmonary disease (COPD), asthma, heart failure and diabetes3 are at increased risk for severe consequences from an RSV infection compared to those without these conditions. RSV can exacerbate these conditions and lead to pneumonia, hospitalisation or death.4

Tony Wood, Chief Scientific Officer, GSK, said: “Today's approval reflects the importance of broadening the benefits of RSV immunisation to adults aged 50-59 who are at increased risk. For those with underlying medical conditions, RSV can have serious consequences, so we are proud to be the first to help protect them from RSV-LRTD.”

The regulatory application was supported by positive results from a phase III trial [NCT05590403]5 evaluating the immune response and safety of GSK’s RSV vaccine in adults aged 50-59, including those at increased risk for RSV-LRTD due to certain underlying medical conditions.

Professor Ann R. Falsey, University of Rochester School of Medicine, said: “I am thrilled that GSK’s RSV vaccine is now approved for adults aged 50-59 at increased risk of RSV-LRTD. When it comes to the risks associated with RSV, age is just a number, an important number, but not the only factor to consider. Many adults in this age group have underlying health conditions that place them at increased risk for serious illness with RSV infection compared with those without these conditions. Now there is a vaccine approved that can help protect them.”

GSK has also filed regulatory submissions to extend the use of its RSV vaccine to adults aged 50-59 at increased risk in Europe, Japan and other geographies with regulatory decisions undergoing review. Trials evaluating the immunogenicity and safety of the vaccine in adults aged 18-49 at increased risk and immunocompromised adults aged 18 and over are expected to read out in H2 2024.

About GSK’s RSV vaccine

Respiratory Syncytial Virus Vaccine, Adjuvanted, contains recombinant RSV glycoprotein F stabilised in the prefusion conformation (RSVPreF3). This antigen is combined with GSK’s proprietary AS01E adjuvant.

In May 2023, the FDA approved GSK’s RSV vaccine for the prevention of lower respiratory tract disease (LRTD) caused by respiratory syncytial virus (RSV) in individuals 60 years of age and older. The use of this vaccine should be in accordance with official recommendations. As with any vaccine, a protective immune response may not be elicited in all vaccinees.

The vaccine has also been approved for the prevention of RSV-LRTD in individuals 60 years of age and older in over 40 countries, including Europe, Japan and US. Regulatory reviews in multiple countries are ongoing. The proposed trade name remains subject to regulatory approval in other markets.

The GSK proprietary AS01 adjuvant system contains STIMULON QS-21 adjuvant licensed from Antigenics Inc, a wholly owned subsidiary of Agenus Inc. STIMULON is a trademark of SaponiQx Inc., a subsidiary of Agenus.

About the NCT05590403 trial

NCT05590403 is a phase III, placebo-controlled, observer-blind, randomised, multi-country immunogenicity trial to evaluate the non-inferiority of the immune response and evaluate safety in participants aged 50 to 59, including those at increased risk for RSV-LRTD compared to older adults aged 60 years and above after a single dose of GSK’s RSV vaccine.

The study assessed the immune response in participants aged 50 to 59 with pre-defined stable chronic diseases leading to an increased risk for RSV disease (n=570). Immune responses in a broader group of participants aged 50-59 years without these pre-defined chronic diseases (n=570) were also evaluated compared to adults aged 60 and older. The trial’s primary endpoints were RSV-A and RSV-B neutralisation titres of both groups at one month after the vaccine administration compared to adults aged 60 and older. There were also safety and immunogenicity secondary and tertiary endpoints. Safety and reactogenicity data were consistent with results from the initial AReSVi-006 data read out. The most common local adverse event was pain. The most common systematic adverse events were myalgia, fatigue and headache, which were largely transient and mild to moderate in intensity.

Results from this trial have been presented at the ACIP meeting of October 2023 and at ReSVinet in February 2024, and have been submitted for peer-reviewed publication. The data are being submitted to other regulators to support potential label expansions.

About RSV in adults

RSV is a common contagious virus affecting the lungs and breathing passages. Adults can be at increased risk for RSV disease due to comorbidities, immune compromised status, or advanced age.4 RSV can exacerbate conditions, including COPD, asthma, and chronic heart failure and can lead to severe outcomes, such as pneumonia, hospitalisation, and death.4 Each year, RSV is estimated to cause approximately 177,000 hospitalisations in adults 65 years and older6 and 42,000 in adults aged 50-64 years old in the US2.

Please see the full US Prescribing Information: https://gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Arexvy/pdf/AREXVY.PDF

https://arexvy.com/

About GSK

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

GSK wins FDA nod to expand label for RSV vaccine

Jun. 08, 2024 7:45 AM ET

GSK plc (GSK) Stock, AGEN Stock

PFE, MRNABy: Dulan Lokuwithana, SA News Editor3 Comments

GSK (NYSE:GSK) announced late Friday that the U.S. FDA approved Arexvy, its vaccine against the respiratory syncytial virus (RSV) for adults aged 50–59 years at increased risk of infection, expanding its current label for older adults.

https://seekingalpha.com/news/4114295-gsk-wins-fda-nod-expand-rsv-vaccine-label?source=content_type%3Areact%7Cfirst_level_url%3Amarket-news%7Csection_asset%3Amain%7Csection%3Ahealthcare

GSK plc (GSK) Stock, AGEN Stock

https://www.gsk.com/en-gb/

https://arexvy.com/

AREXVY is an FDA-approved vaccine for the prevention of lower respiratory tract disease (LRTD) caused by respiratory syncytial virus in people 60 years of age and older.

RYTELO™ (imetelstat)

Geron Announces FDA Approval of RYTELO™ (imetelstat), a First-in-Class Telomerase Inhibitor, for the Treatment of Adult Patients with Lower-Risk MDS with Transfusion-Dependent Anemia

June 6, 2024 Download(opens in new window)

Approval across ESA ineligible and ESA relapsed/refractory patients with LR-MDS with transfusion-dependent anemia, regardless of ring sideroblast (RS) status
Durable and sustained red blood cell transfusion independence, increases in hemoglobin levels and reduction in transfusion burden observed across key LR-MDS subgroups in the IMerge Phase 3 clinical trial; the most common Grade 3/4 adverse reactions were thrombocytopenia and neutropenia, which were generally manageable and short-lived
Lower-risk MDS is a progressive blood cancer with high unmet need, where many patients with anemia become dependent on red blood cell transfusions, which can be associated with clinical consequences and decreased quality of life
Conference call with Geron management scheduled at 8am ET on Friday, June 7, 2024

FOSTER CITY, Calif.--(BUSINESS WIRE)-- Geron Corporation (Nasdaq: GERN), a commercial-stage biopharmaceutical company aiming to change lives by changing the course of blood cancer, today announced that the U.S. Food and Drug Administration (FDA) has approved RYTELO™ (imetelstat) for the treatment of adult patients with low- to intermediate-1 risk myelodysplastic syndromes (MDS) with transfusion-dependent (TD) anemia requiring four or more red blood cell units over eight weeks who have not responded to or have lost response to or are ineligible for erythropoiesis-stimulating agents (ESA).

“With the approval and availability of RYTELO, we believe eligible patients with lower-risk MDS can potentially experience meaningful clinical benefit, particularly the potential for greater than 24 weeks of freedom from the burden of red blood cell transfusions and symptomatic anemia,” said John A. Scarlett, M.D., Geron’s Chairman and Chief Executive Officer. “The approval of RYTELO as the first telomerase inhibitor is a testament to the power of our science and the passion of our people to innovate in the field of blood cancer. As we celebrate today’s momentous milestone, I would like to thank the patients and families, advocates, clinicians, study coordinators and site personnel, scientists, and Geron employees and collaborators past and present whose participation was integral to this achievement and to supporting our transformation into a commercial company.”

Lower-risk myelodysplastic syndromes (LR-MDS) is a blood cancer that often progresses to require increasingly intensified management of key symptoms such as anemia and resulting fatigue1. These symptomatic LR-MDS patients frequently become red blood cell transfusion dependent, which has been shown to be associated with short- and long-term clinical consequences that reduce quality of life and shorten survival2,3. There is a high unmet need for many LR-MDS patients, particularly those with characteristics having poorer prognosis. Current treatment options for those failing ESA are limited to select sub-populations and there is an unmet need for treatments that can provide extended and continuous red blood cell transfusion independence.

Approval Based on Results from IMerge Phase 3 Clinical Trial

“For patients with lower-risk MDS and anemia who are transfusion dependent, we have very few options today and often cycle through available therapies, making the approval of RYTELO potentially practice changing for us,” said Rami Komrokji, MD, Vice Chair, Malignant Hematology Department, Moffitt Cancer Center, who was an investigator of the pivotal IMerge clinical trial. “What is exciting about RYTELO is the totality of the clinical benefit across LR-MDS patients irrespective of ring sideroblast status or high transfusion burden, including sustained and durable transfusion independence and increases in hemoglobin levels, all within a well-characterized safety profile of generally manageable cytopenias. The treatment goal for patients with LR-MDS and anemia is transfusion-independence and before today, this wasn’t possible for many patients.”

The FDA approval of RYTELO is based on results from the IMerge Phase 3 clinical trial, published in The Lancet 4. The IMerge trial met its primary and key secondary endpoints, with RYTELO demonstrating significantly higher rates of red blood cell transfusion independence (RBC-TI) versus placebo for at least eight consecutive weeks (RYTELO 39.8% [95% CI 30.9–49.3]; placebo 15.0% [7.1–26.6]; p<0.001) and for at least 24 weeks (RYTELO 28.0% [95% CI 20.1-37.0]; placebo 3.3% [95% CI 0.4-11.5]; p<0.001). RBC-TI was durable and sustained in the RYTELO treated population, with a median RBC-TI duration for 8-week responders and 24-week responders of approximately 1 year and 1.5 years, respectively.

In an exploratory analysis of RYTELO-treated patients achieving ≥8-week RBC-TI, median increases in hemoglobin were 3.6 g/dL for RYTELO and 0.8 g/dL for placebo. Clinically meaningful efficacy results were observed across key MDS subgroups irrespective of ring sideroblast (RS) status, baseline transfusion burden and IPSS risk category.

In the IMerge trial, the safety profile of RYTELO was well-characterized with generally manageable and short-lived thrombocytopenia and neutropenia, which are familiar side effects for hematologists who are experienced with managing cytopenias. The most common Grade 3/4 adverse reactions were neutropenia (72%) and thrombocytopenia (65%), which lasted a median duration of less than two weeks, and in more than 80% of patients were resolved to Grade < 2 in under four weeks. Cytopenias were generally manageable with dose modifications. The intravenous administration of RYTELO every four weeks aligns to routine blood count monitoring for these patients.

The most common adverse reactions (incidence ≥10% with a difference between arms of >5% compared to placebo), including laboratory abnormalities, were decreased platelets (thrombocytopenia), decreased white blood cells, decreased neutrophils (neutropenia), increased aspartate aminotransferase (AST), increased alkaline phosphatase (ALP), increased alanine aminotransferase (ALT), fatigue, prolonged partial thromboplastin time, arthralgia/myalgia, COVID-19 infections, and headache. Clinically relevant adverse reactions in < 5% of patients who received RYTELO included febrile neutropenia, sepsis, gastrointestinal hemorrhage, and hypertension.

Conference Call Details

A conference call with Geron management is scheduled at 8am Eastern Time on Friday, June 7, 2024, to discuss the FDA approval and launch of RYTELO. To access the webcast and slides, please visit the Investors & Media page. Participants may access the webcast by registering online using the following link, https://events.q4inc.com/attendee/923992744.

About RYTELO™ (imetelstat)

RYTELO™ (imetelstat) is an FDA-approved oligonucleotide telomerase inhibitor for the treatment of adult patients with low-to-intermediate-1 risk myelodysplastic syndromes (LR-MDS) with transfusion-dependent anemia requiring four or more red blood cell units over eight weeks who have not responded to or have lost response to or are ineligible for erythropoiesis-stimulating agents (ESAs). It is indicated to be administered as an intravenous infusion over two hours every four weeks.

RYTELO is a first-in-class treatment that works by inhibiting telomerase enzymatic activity. Telomeres are protective caps at the end of chromosomes that naturally shorten each time a cell divides. In LR-MDS, abnormal bone marrow cells often express the enzyme telomerase, which rebuilds those telomeres, allowing for uncontrolled cell division. Developed and exclusively owned by Geron, RYTELO is the first and only telomerase inhibitor approved by the U.S. Food and Drug Administration.

Geron aims to ensure broad access to RYTELO for eligible patients. Accordingly, our REACH4RYTELO™ Patient Support Program provides a range of resources that support access and affordability to eligible patients prescribed RYTELO.

About Geron

Geron is a commercial-stage biopharmaceutical company aiming to change lives by changing the course of blood cancer. Our first-in-class telomerase inhibitor RYTELO™ (imetelstat) is FDA-approved for the treatment of adult patients with lower-risk MDS with transfusion dependent anemia. We are also conducting a pivotal Phase 3 clinical trial of imetelstat in JAK-inhibitor relapsed/refractory myelofibrosis (R/R MF), as well as studies in other hematologic malignancies. Inhibiting telomerase activity, which is increased in malignant stem and progenitor cells in the bone marrow, aims to potentially reduce proliferation and induce death of malignant cells. To learn more, visit www.geron.com or follow us on LinkedIn.

Source: Geron Corporation

Geron jumps as FDA approves lead asset for blood cancer

Jun. 07, 2024 6:39 AM ET

Geron Corporation (GERN) StockBMY, MRK

By: Dulan Lokuwithana, SA News Editor86 Comments

Update 6.39 AM EST: Adds latest share price move

Geron (NASDAQ:GERN) shares added ~17% premarket Friday after the U.S. Food and Drug Administration (FDA) approved its lead asset, imetelstat, as a late-line option for a type of blood cancer called myelodysplastic syndromes (MDS).

The company announced in a statement late Thursday that imetelstat, a telomerase inhibitor, will, therefore, be available in the U.S. as Rytelo for adults with low- to intermediate-risk MDS who have developed anemia requiring blood transfusions.

https://seekingalpha.com/news/4113925-geron-stock-gains-rytelo-approval?source=content_type%3Areact%7Cfirst_level_url%3Amarket-news%7Csection_asset%3Amain%7Csection%3Ahealthcare

Geron Corporation (GERN) Stock

https://www.geron.com/

https://www.geron.com/research-and-development/

Our pipeline

Tagrisso (osimertinib)

Tagrisso granted Priority Review in the US for patients with unresectable, Stage III EGFR-mutated lung cancer

PUBLISHED10 June 2024

Decision based on LAURA Phase III trial results which extended
median progression-free survival by more than three years

Tagrisso also granted Breakthrough Therapy Designation in US in this setting

AstraZeneca’s supplemental New Drug Application (sNDA) for has been accepted and granted Priority Review in the US for the treatment of adult patients with unresectable, Stage III epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC) after chemoradiotherapy (CRT). If approved, Tagrisso will be indicated for EGFRm patients whose tumours have exon 19 deletions or exon 21 (L858R) mutations.

The Food and Drug Administration (FDA) grants Priority Review to applications for medicines that, if approved, would offer significant improvements over available options by demonstrating safety or efficacy improvements, preventing serious conditions or enhancing patient compliance.1 The Prescription Drug User Fee Act date, the FDA action date for their regulatory decision, is anticipated during the fourth quarter of 2024.

Tagrisso was also recently granted Breakthrough Therapy Designation (BTD) by the FDA in this setting. BTD accelerates the development and regulatory review of potential new medicines intended to treat a serious condition and address a significant unmet medical need.2

Each year in the US, there are nearly 200,000 people diagnosed with lung cancer, and 80-85% of these patients are diagnosed with NSCLC, the most common form of lung cancer.3-5 Approximately 15% of NSCLC patients in the US have EGFR mutations.6 Nearly one in five newly diagnosed individuals with NSCLC are unresectable.7

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “Priority Review of Tagrisso in this early-stage curative setting is important for patients who currently have no targeted treatments available. We look forward to close collaboration with the FDA on an accelerated path to bring Tagrisso to patients as a potential new standard of care as quickly as possible. Tagrisso continues to serve patients as a backbone therapy in EGFR-mutated lung cancer, extending progression-free survival in the LAURA trial by more than three years and reinforcing the importance of testing for EGFR mutations at the time of diagnosis.”

The sNDA is based on data from the LAURA Phase III trial recently presented during the Plenary Session at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting and simultaneously published in The New England Journal of Medicine.

In the trial, Tagrisso reduced the risk of disease progression or death by 84% compared to placebo (hazard ratio [HR] 0.16; 95% confidence interval [CI] 0.10-0.24; p<0.001) as assessed by blinded independent central review (BICR). Median progression-free survival (PFS) was 39.1 months in patients treated with Tagrisso versus 5.6 months for placebo. Importantly, a clinically meaningful PFS benefit was observed across all prespecified subgroups including sex, race, type of EGFR mutation, age, smoking history, and prior CRT.

Overall survival (OS) data showed a favourable trend for Tagrisso, although data were not mature at the time of this analysis. The trial will continue to assess OS as a secondary endpoint.

Safety results and discontinuation rates due to adverse events were consistent with its known profile and no new safety concerns were identified.

Tagrisso is approved as monotherapy in more than 100 countries including in the US, EU, China and Japan. Approved indications include for 1st-line treatment of patients with locally advanced or metastatic EGFRm NSCLC, locally advanced or metastatic EGFR T790M mutation-positive NSCLC, and adjuvant treatment of early-stage EGFRm NSCLC. Tagrisso with the addition of chemotherapy is also approved in the US and several other countries for 1st-line treatment of patients with locally advanced or metastatic EGFRm NSCLC.

Notes

Lung cancer
Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-fifth of all cancer deaths.8 Lung cancer is broadly split into NSCLC and small cell lung cancer.4 The majority of all NSCLC patients are diagnosed with advanced disease.9

Patients with EGFRm NSCLC are particularly sensitive to treatment with an EGFR-tyrosine kinase inhibitor (EGFR-TKI) which blocks the cell-signalling pathways that drive the growth of tumour cells.10

LAURA
LAURA is a randomised, double-blind, placebo-controlled, multi-centre, global Phase III trial in patients with unresectable, Stage III EGFRm NSCLC whose disease has not progressed following definitive platinum‑based CRT. Patients were treated with Tagrisso 80mg once daily oral tablets until disease progression, unacceptable toxicity or other discontinuation criteria were met. Upon progression, patients in the placebo arm were permitted to be treated with Tagrisso.

The trial enrolled 216 patients in more than 145 centres across more than 15 countries, including in the US, Europe, South America and Asia. This is the analysis of the primary endpoint of PFS. The trial is ongoing and will continue to assess the secondary endpoint of OS.

Tagrisso
Tagrisso (osimertinib) is a third-generation, irreversible EGFR-TKI with proven clinical activity in NSCLC, including against central nervous system (CNS) metastases. Tagrisso (40mg and 80mg once-daily oral tablets) has been used to treat nearly 800,000 patients across its indications worldwide and AstraZeneca continues to explore Tagrisso as a treatment for patients across multiple stages of EGFRm NSCLC.

There is an extensive body of evidence supporting the use of Tagrisso in EGFRm NSCLC. Tagrisso is the only targeted therapy to improve patient outcomes in early-stage disease in the ADAURA Phase III trial, locally advanced stages in the LAURA Phase III trial and late-stage disease in the FLAURA Phase III trial and FLAURA2 Phase III trial.

As part of AstraZeneca’s ongoing commitment to treating patients as early as possible in lung cancer, Tagrisso is also being investigated in the neoadjuvant setting in the NeoADAURA Phase III trial with results expected later this year and in the early-stage adjuvant resectable setting in the ADAURA2 Phase III trial.

The Company is also researching ways to address tumour mechanisms of resistance through the SAVANNAH and ORCHARD Phase II trials, and the SAFFRON Phase III trial, which test Tagrisso plus savolitinib, an oral, potent and highly selective MET TKI, as well as other potential new medicines.

https://www.tagrisso.com/

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 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 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 social media @AstraZeneca.

Contacts
For details on how to contact the Investor Relations Team, please click here. For Media contacts, click here.

AstraZeneca’s Tagrisso gets FDA priority review in lung cancer subtype

Jun. 10, 2024 5:55 AM ET

AstraZeneca PLC (AZN) Stock

By: Preeti Singh, SA News Editor

AstraZeneca's (NASDAQ:AZN) supplemental New Drug Application for its tyrosine kinase inhibitor, Tagrisso (osimertinib), has been granted priority review in the U.S. to treat adult patients with unresectable, Stage III EGFR-mutated lung cancer after chemoradiotherapy.

https://seekingalpha.com/news/4114382-astrazenecas-tagrisso-gets-fda-priority-review-in-lung-cancer-subtype?mailingid=35660425&messageid=2900&serial=35660425.1573&source=email_2900&utm_campaign=rta-stock-news&utm_content=link-1&utm_medium=email&utm_source=seeking_alpha&utm_term=35660425.1573

AstraZeneca PLC (AZN) Stock

https://www.astrazeneca.com/

https://www.tagrisso.com/

What is TAGRISSO? TAGRISSO is a prescription medicine used to treat adults with non-small cell lung cancer (NSCLC) that has certain abnormal epidermal growth factor receptor (EGFR) gene(s): to help prevent your lung cancer from coming back after your tumor(s) has been removed by surgery, or as your first treatment when your lung cancer has spread to other parts of the body (metastatic), or when your lung cancer has spread to other parts of the body (metastatic) and you have had previous treatment with an EGFR tyrosine kinase inhibitor (TKI) medicine that did not work or is no longer working, or in combination with pemetrexed and platinum-based chemotherapy, as your first treatment when your lung cancer has spread to nearby tissues (locally advanced) or to other parts of the body (metastatic). Your healthcare provider will perform a test to make sure that TAGRISSO is right for you. It is not known if TAGRISSO is safe and effective in children.

RINVOQ® (upadacitinib)

June 04, 2024

RINVOQ® (upadacitinib) Now Available for Pediatric Patients Two Years and Older with Polyarticular Juvenile Idiopathic Arthritis and Psoriatic Arthritis

– First indications of RINVOQ (upadacitinib) for pediatric patients two years of age and older1
– RINVOQ is now approved for eight indications across immune-mediated inflammatory diseases1

NORTH CHICAGO, Ill., June 4, 2024 /PRNewswire/ -- AbbVie (NYSE: ABBV) today announced that RINVOQ® (upadacitinib) is indicated in the U.S. for the treatment of pediatric patients two years of age and older with active polyarticular juvenile idiopathic arthritis (pJIA) as well as psoriatic arthritis (PsA), provided they have had an inadequate response or intolerance to one or more tumor necrosis factor (TNF) blockers. Additionally, a new weight-based oral solution, RINVOQ® LQ (upadacitinib), is now available as an option for these pediatric populations.1

Experience the interactive Multimedia News Release here: https://www.multivu.com/players/English/9254951-rinvoq-upadacitinib-available-pediatric-polyarticular-juvenile-idiopathic-and-psoriatic-arthritis/

"RINVOQ has been an important addition to the treatment landscape for various rheumatic diseases, helping adult patients achieve meaningful disease control," said Roopal Thakkar, M.D., senior vice president, chief medical officer, global therapeutics, AbbVie. "AbbVie is proud to now offer RINVOQ as a tablet and oral solution to some of our youngest patients."

Nearly 300,000 children and adolescents in the U.S. have a form of juvenile idiopathic arthritis, which includes pJIA and PsA.2-3 The polyarticular form of juvenile idiopathic arthritis is characterized by inflammation in five or more joints that persists for at least six weeks in children and adolescents before 16 years of age.2 The psoriatic arthritis form of juvenile idiopathic arthritis is characterized by both joint inflammation and skin lesions associated with psoriasis.4 These chronic diseases can be painful and debilitating and, if left untreated, may lead to joint damage.5-6 Despite treatment advancements, achieving long-term remission remains elusive for many patients living with a form of juvenile idiopathic arthritis, with approximately half requiring ongoing treatment into adulthood.7-8

"Pediatric patients with pJIA and PsA can be severely limited in their ability to complete daily physical tasks and participate in everyday activities. Understanding their needs today and knowing the likelihood of disease in adulthood underscores the need for additional treatment options," said Aarat Patel, M.D., adult and pediatric rheumatology, Bon Secours Rheumatology Center of St. Mary's Hospital. "Having a treatment option available for patients who do not respond well to a TNFi addresses a need for the healthcare community, patients, and their families."

Data Supporting the Approvals1
The approvals of RINVOQ and RINVOQ LQ oral solution are supported by evidence from well-controlled studies of RINVOQ in adult patients with rheumatoid arthritis (RA) and PsA, pharmacokinetic data from adult patients with RA and PsA, as well as 51 pediatric patients with juvenile idiopathic arthritis with active polyarthritis, in addition to safety data from 83 pediatric patients two to less than 18 years of age with juvenile idiopathic arthritis with active polyarthritis. Upadacitinib plasma exposures in pediatric patients with pJIA and PsA at the recommended dosage are predicted to be comparable to those observed in adults with RA and PsA based on population pharmacokinetic modeling and simulation.

RINVOQ*/RINVOQ LQ Safety Considerations

Overall, the safety profile observed in pediatric patients with juvenile idiopathic arthritis with active polyarthritis treated with RINVOQ/RINVOQ LQ was consistent with the known safety profile of RINVOQ.
RINVOQ may cause serious side effects, including:
- Serious infections. RINVOQ can lower ability to fight infections. Serious infections, some fatal, occurred, including tuberculosis (TB) and infections caused by bacteria, fungi, or viruses.
- Increased risk of death in people 50 years and older who have at least 1 heart disease (cardiovascular) risk factor.
- Cancer and immune system problems. Increased risk of some cancers, including lymphoma and skin. Current or past smokers have higher risk for lymphoma and lung cancer.
- Increased risk of major cardiovascular (CV) events, such as heart attack, stroke, or death, in people 50 years and older who have at least 1 heart disease (CV) risk factor, especially in current or past smokers.
- Blood clots, some fatal, in veins of the legs or lungs and arteries. This occurred more often in people 50 years and older who have at least 1 heart disease (CV) risk factor.
- Serious allergic reactions. Do not take if allergic to RINVOQ or its ingredients.
- Tears in the stomach or intestines; changes in certain laboratory test results.

*Unless otherwise stated, "RINVOQ" in the Safety Considerations refers to RINVOQ and RINVOQ LQ.

For more information about RINVOQ, visit RINVOQ.com.

Patient Access and Support
AbbVie is committed to helping people access RINVOQ and other medicines, including offering a patient support program and a co-pay card that may reduce out-of-pocket costs to $5 per month for eligible, commercially insured patients. For those with limited or no health insurance, AbbVie offers myAbbVie Assist, a patient assistance program that provides RINVOQ at no charge to those who qualify. For more details, please visit AbbVie.com/myAbbVieAssist.

About RINVOQ® (upadacitinib)
Discovered and developed by AbbVie scientists, RINVOQ is a JAK inhibitor that is being studied in several immune-mediated inflammatory diseases. In human leukocyte cellular assays, RINVOQ inhibited cytokine-induced STAT phosphorylation mediated by JAK1 and JAK1/JAK3 more potently than JAK2/JAK2 mediated STAT phosphorylation. The relevance of inhibition of specific JAK enzymes to therapeutic effectiveness and safety is not currently known.1

Phase 3 trials of RINVOQ in alopecia areata, ankylosing spondylitis, atopic dermatitis, axial spondyloarthritis, Crohn's disease, giant cell arteritis, hidradenitis suppurativa, psoriatic arthritis, rheumatoid arthritis, systemic lupus erythematosus (SLE), Takayasu arteritis, ulcerative colitis and vitiligo are ongoing.9,10,11,12,13,14,15,16,17,18,19,20,21,22

https://www.rinvoq.com/

RINVOQ® (upadacitinib) U.S. Uses and Important Safety Information

RINVOQ is a prescription medicine used to treat:

Adults with moderate to severe rheumatoid arthritis (RA) when 1 or more medicines called tumor necrosis factor (TNF) blockers have been used, and did not work well or could not be tolerated.
Adults with active psoriatic arthritis (PsA) when 1 or more medicines called TNF blockers have been used, and did not work well or could not be tolerated.
Adults with active ankylosing spondylitis (AS) when 1 or more medicines called TNF blockers have been used, and did not work well or could not be tolerated.
Adults with active non-radiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation when a TNF blocker medicine has been used, and did not work well or could not be tolerated.
Adults with moderate to severe ulcerative colitis (UC) when 1 or more medicines called TNF blockers have been used, and did not work well or could not be tolerated.
Adults with moderate to severe Crohn's disease (CD) when 1 or more medicines called TNF blockers have been used, and did not work well or could not be tolerated.

It is not known if RINVOQ is safe and effective in children with ankylosing spondylitis, non-radiographic axial spondyloarthritis, ulcerative colitis, or Crohn's disease.

Adults and children 12 years of age and older with moderate to severe eczema (atopic dermatitis [AD]) that did not respond to previous treatment and their eczema is not well controlled with other pills or injections, including biologic medicines, or the use of other pills or injections is not recommended.

It is not known if RINVOQ is safe and effective in children under 12 years of age with atopic dermatitis.

It is not known if RINVOQ LQ is safe and effective in children with atopic dermatitis.

RINVOQ/RINVOQ LQ is a prescription medicine used to treat:

Children 2 years of age and older with active polyarticular juvenile idiopathic arthritis (pJIA) when 1 or more medicines called TNF blockers have been used, and did not work well or could not be tolerated.
Children 2 to less than 18 years of age with active psoriatic arthritis (PsA) when 1 or more medicines called TNF blockers have been used, and did not work well or could not be tolerated.

It is not known if RINVOQ/RINVOQ LQ is safe and effective in children under 2 years of age with polyarticular juvenile idiopathic arthritis or psoriatic arthritis.

Please click here for the Full Prescribing Information and Medication Guide.

About AbbVie in Rheumatology
For more than 20 years, AbbVie has been dedicated to improving care for people living with rheumatic diseases. Anchored by a longstanding commitment to discovering and delivering transformative therapies, we pursue cutting-edge science that improves our understanding of promising new pathways and targets, ultimately helping more people living with rheumatic diseases reach their treatment goals. For more information, visit AbbVie in rheumatology.

About AbbVie
AbbVie's mission is to discover and deliver innovative medicines and solutions that solve serious health issues today and address the medical challenges of tomorrow. We strive to have a remarkable impact on people's lives across several key therapeutic areas – immunology, oncology, neuroscience, and eye care – and products and services in our Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on LinkedIn, Facebook, Instagram, X (formerly Twitter), and YouTube.

https://seekingalpha.com/symbol/ABBV

https://www.abbvie.com/

https://www.rinvoq.com/

USES RINVOQ is a prescription medicine used to treat: Adults with moderate to severe rheumatoid arthritis (RA) when 1 or more medicines called tumor necrosis factor (TNF) blockers have been used, and did not work well or could not be tolerated. Adults with active psoriatic arthritis (PsA) when 1 or more medicines called TNF blockers have been used, and did not work well or could not be tolerated. Adults with active ankylosing spondylitis (AS) when 1 or more medicines called TNF blockers have been used, and did not work well or could not be tolerated. Adults with active non-radiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation when a TNF blocker medicine has been used, and did not work well or could not be tolerated. Adults with moderate to severe ulcerative colitis (UC) when 1 or more medicines called TNF blockers have been used, and did not work well or could not be tolerated. Adults with moderate to severe Crohn’s disease (CD) when 1 or more medicines called TNF blockers have been used, and did not work well or could not be tolerated. It is not known if RINVOQ is safe and effective in children with ankylosing spondylitis, non-radiographic axial spondyloarthritis, ulcerative colitis, or Crohn’s disease. Adults and children 12 years of age and older with moderate to severe eczema (atopic dermatitis [AD]) that did not respond to previous treatment and their eczema is not well controlled with other pills or injections, including biologic medicines, or the use of other pills or injections is not recommended. It is not known if RINVOQ is safe and effective in children under 12 years of age with atopic dermatitis. It is not known if RINVOQ LQ is safe and effective in children with atopic dermatitis.

SARCLISA® (isatuximab-irfc) injection

Press Release: ASCO: Sarclisa is first anti-CD38 to significantly improve progression-free survival in combination with VRd for newly diagnosed transplant-ineligible multiple myeloma in phase 3

June 3, 2024 Download PDF

ASCO: Sarclisa is first anti-CD38 to significantly improve progression-free survival in combination with VRd for newly diagnosed transplant-ineligible multiple myeloma in phase 3

Sarclisa, in combination with standard-of-care bortezomib, lenalidomide and dexamethasone (VRd) followed by Sarclisa-Rd reduced the risk of recurrence or death by 40% versus VRd followed by Rd in the investigational use for transplant-ineligible newly diagnosed multiple myeloma patients
Key primary endpoint of progression-free survival met, demonstrating Sarclisa's potential as a first-in-class combination to address gaps in care for newly diagnosed transplant-ineligible patients
Full data simultaneously published in NEJM and formed the basis of regulatory submissions

Paris, June 3, 2024. Data from the IMROZ phase 3 study demonstrated Sarclisa (isatuximab) in combination with standard-of-care bortezomib, lenalidomide and dexamethasone (VRd) followed by Sarclisa-Rd (the IMROZ regimen) significantly reduced the risk of disease progression or death by 40%, compared to VRd followed by Rd in patients with newly diagnosed multiple myeloma (NDMM) not eligible for transplant. IMROZ is the first global phase 3 study of an anti-CD38 monoclonal antibody in combination with standard-of-care VRd to significantly improve PFS and show deep responses in this patient population who often have poor prognoses. The results were shared in an oral presentation at the American Society of Clinical Oncology (ASCO) annual meeting and simultaneously published in the New England Journal of Medicine (NEJM).

The use of Sarclisa in combination with VRd in transplant-ineligible NDMM is investigational and has not been fully evaluated by any regulatory authority.

Thierry Facon, MD
Professor of Haematology in the Department of Haematology, Lille University Hospital, Lille, France, member of French Academy of Medicine and IMROZ Principal Investigator
“The significant progression-free survival benefit observed with Sarclisa combination therapy compared to VRd is important and encouraging for patients with newly diagnosed multiple myeloma. Effective frontline therapy has the potential to modify the course of the disease, which is a key outcome for transplant-ineligible patients who often face high rates of attrition in later lines of therapy. The IMROZ results demonstrate the promise of Sarclisa as a backbone to frontline therapy, which may improve long-term outcomes for this incurable disease.”

Key Results
IMROZ is a global, randomized, multi-center, open-label study. At the data cut-off of September 26, 2023, through the median follow-up of 59.7 months, the following were observed for Sarclisa-VRd compared to VRd:

Primary endpoint

40% reduction in the risk of disease progression or death for patients treated with Sarclisa-VRd versus VRd (HR 0.596; 98.5% CI: 0.406 to 0.876; p=0.0005). At the median follow-up of 59.7 months, the median PFS with the Sarclisa-VRd combination was not reached versus 54.3 months with VRd.
The estimated PFS at 60 months was 63.2% for patients treated with Sarclisa-VRd versus 45.2% for VRd.

Secondary endpoints

Approximately three-quarters (74.7%) of patients treated with Sarclisa-VRd achieved a complete response (CR) compared to 64.1% of patients taking VRd (OR 1.7; 95% CI: 1.097-2.5; p=0.008).
More than half (55.5%) of patients treated with Sarclisa-VRd achieved MRD negative CR compared to 40.9% of patients taking VRd (OR 1.8; 95% CI: 1.229-2.646; p=0.0013).
MRD was sustained for at least 12 months among nearly half (46.8%) of patients in the Sarclisa-VRd arm compared to less than one-quarter (24.3%) of patients taking VRd (OR 2.7; 95% CI: 1.799-4.141).

At the date of data cut-off, 47.2% of patients (125/263) treated with Sarclisa-VRd and 24.3% of patients (44/181) treated with VRd were still on treatment. The median treatment duration for the Sarclisa-VRd combination was 53.2 months vs. 31.3 months for VRd.

The safety and tolerability of Sarclisa observed in this study was consistent with the established safety profile of Sarclisa-VRd with no new safety signals observed. Grade ≥3 treatment-emergent adverse events (TEAE) occurred in 91.6% of patients taking Sarclisa-VRd and 84% of patients taking VRd. Treatment-emergent events (TAE) of any grade led to treatment discontinuation in 22.8% of patients taking Sarclisa-VRd and 26% of patients taking VRd.

Peter C. Adamson
Global Development Head, Oncology
“Over the last 20 years, the pace of multiple myeloma research has continued to accelerate, paving the way for treatment advancements with potential to improve outcomes for patients. With our commitment to help lead the way for patients with this disease, we welcomed the IMROZ results presented at ASCO, and now published in NEJM, which demonstrate Sarclisa’s potential to improve progression-free survival in patients who are newly diagnosed and transplant ineligible. We want to express our deep gratitude to the patients, their families and investigators for their dedication to clinical research.”

Advancing Sarclisa in Newly Diagnosed Multiple Myeloma
The US Food and Drug Administration (FDA) accepted for Priority Review the supplemental Biologics License Application (sBLA) for the investigational use of Sarclisa in combination with VRd for the treatment of patients with transplant-ineligible NDMM. A regulatory submission is also under review in the European Union (EU). If approved, Sarclisa would be the first anti-CD38 therapy in combination with standard-of-care VRd in newly diagnosed patients not eligible for transplant, which would be the third indication for Sarclisa in multiple myeloma.

The IMROZ data will also be presented during the plenary scientific session at the European Hematology Association (EHA) Annual Congress on June 15, selected as one of the top six abstracts to be featured at the congress. There will be two additional oral presentations at EHA featuring results from phase 3 studies of Sarclisa in NDMM. Additionally, the IMROZ abstract was hand-selected to be included in the 2024 Best of ASCO program, held later in the summer of 2024, following the ASCO Annual Meeting.

Sanofi’s oncology pipeline and portfolio prioritize areas of high unmet need for difficult-to-treat cancers, including multiple myeloma, which remains an incurable disease despite recent advances in treatment.

About the IMROZ study
The randomized, multi-center, open-label IMROZ phase 3 clinical study enrolled 446 patients with newly diagnosed, transplant-ineligible multiple myeloma (MM) across 21 countries and 104 centers. During the study, Sarclisa was administered through an intravenous infusion at a dose of 10 mg/kg once weekly for five weeks during first 42-day cycle and once every two weeks in cycles 2 to 4 in combination with subcutaneous bortezomib, oral lenalidomide and intravenous or oral dexamethasone. Then Sarclisa was administered every 2 weeks from cycle 5 to 17 and every 4 weeks in cycles 18+ during 28-day cycles in combination with lenalidomide and dexamethasone at the standard dose, until disease progression, unacceptable safety profile or patient’s decision to stop the study treatment.

The primary endpoint was progression-free survival. Key secondary endpoints include complete response rate, MRD negativity rate for patients with a complete response, very good partial response or better rate, overall survival. Other secondary endpoints are: overall response rate, time to progression, duration of response, time to first response, time to best response, progression-free survival on next line of therapy, progression-free survival by MRD status, sustained MRD negativity greater than or equal to 12 months rate, safety, pharmacokinetic profile, immunogenicity, disease-specific and generic health-related quality of life, disease and treatment-related symptoms, health state utility, and health status.1

The use of Sarclisa in combination with VRd in transplant-ineligible newly diagnosed MM is investigational and has not been fully evaluated by any regulatory authority.

About Sarclisa
Sarclisa is a monoclonal antibody that binds to a specific epitope on the CD38 receptor on multiple myeloma (MM) cells, inducing distinct antitumor activity. It is designed to work through multiple mechanisms of action including programmed tumor cell death (apoptosis) and immunomodulatory activity. CD38 is highly and uniformly expressed on the surface of MM cells, making it a potential target for antibody-based therapeutics such as Sarclisa.

Based on the ICARIA-MM phase 3 study, Sarclisa is approved in >50 countries, including the US and EU, in combination with pomalidomide and dexamethasone for the treatment of patients with relapsed refractory MM (RRMM) who have received ≥2 prior therapies, including lenalidomide and a proteasome inhibitor and who progressed on last therapy. Based on the IKEMA phase 3 study, Sarclisa is also approved in 50 countries in combination with carfilzomib and dexamethasone, including in the US for the treatment of patients with RRMM who have received 1–3 prior lines of therapy and in the European Union for patients with MM who have received at least 1 prior therapy. In the US, the generic name for Sarclisa is isatuximab-irfc, with irfc as the suffix designated in accordance with Nonproprietary Naming of Biological Products Guidance for Industry issued by the US Food and Drug Administration (FDA).

Sarclisa continues to be evaluated in multiple ongoing phase 3 clinical studies in combination with current standard treatments across the MM treatment continuum. It is also under investigation for the treatment of other hematologic malignancies, and its safety and efficacy have not been evaluated by any regulatory authority outside of its approved indication.

For more information on Sarclisa clinical studies, please visit www.clinicaltrials.gov.

https://www.sarclisa.com/

About multiple myeloma
MM is the second most common hematologic malignancy,2 with more than 180,000 new diagnoses of MM worldwide yearly.3 Despite available treatments, MM remains an incurable malignancy with an estimated 52% five-year survival rate for newly diagnosed patients.4 Since MM does not have a cure, most patients will relapse. Since MM does not have a cure, most patients will relapse. Relapsed MM is the term for when the cancer returns after treatment or a period of remission. Refractory MM refers to when the cancer does not respond or no longer responds to therapy.

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 the world, 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

Attachment

Press Release

Sanofi says Sarclisa improves progression-free survival in some multiple myeloma patients

Jun. 03, 2024 6:42 PM ET

Sanofi (SNY) StockJNJ, TAK

By: Jonathan Block, SA News Editor

New phase 3 data found that Sanofi's (NASDAQ:SNY) multiple myeloma treatment Sarclisa (isatuximab) in combination with standard-of-care therapy reduced the risk of recurrence or death by 40% compared to standard of care alone.
https://seekingalpha.com/news/4112515-sanofi-says-sarclisa-improves-progression-free-survival-in-some-multiple-myeloma-patients
Sanofi (SNY) Stock
https://www.sanofi.com/en
https://www.sarclisa.com/

What is SARCLISA? SARCLISA is a prescription medicine used in combination with: The medicines pomalidomide and dexamethasone, to treat adults who have received at least 2 prior therapies including lenalidomide and a proteasome inhibitor to treat multiple myeloma. The medicines carfilzomib and dexamethasone, to treat adults with multiple myeloma who have already received 1 to 3 lines of treatment and they did not work or are no longer working. It is not known if SARCLISA is safe and effective in children.

TECARTUS® (brexucabtagene autoleucel) suspension for intravenous infusion

June 03, 2024

Kite’s Tecartus® Demonstrates Sustained Overall Survival in Adult Patients With Relapsed/Refractory B-cell Acute Lymphoblastic Leukemia

-- After More Than Four Years of Follow-up in the Pivotal ZUMA-3 Study, Median Overall Survival (OS) was 26 Months and the OS Rate was 40% at 48 Months --

-- Survival Benefit was Seen Regardless of Age, Prior Treatment or Subsequent Allogeneic Stem Cell Transplant Status --

-- Data Being Presented at the 2024 American Society of Clinical Oncology Annual Meeting --

SANTA MONICA, Calif.--(BUSINESS WIRE)-- Kite, a Gilead Company (Nasdaq: GILD), today announced updated, four-year overall survival (OS) data from the pivotal ZUMA-3 study evaluating the CAR T-cell therapy Tecartus® (brexucabtagene autoleucel) in adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL). The findings showed a median OS of 25.6 months and a four-year OS rate of 40% (95% CI, 28-52) in all treated patients with a safety profile consistent with that observed in the three-year analysis. The results were presented today in a poster presentation (Abstract #6531) at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting.

“B-cell acute lymphoblastic leukemia is a rare and aggressive form of blood cancer associated with poor prognosis – with a median survival of less than eight months in those with relapsed or refractory disease – so to see 40% of these patients treated with one infusion of Brexu-cel still alive after four years is meaningful indeed,” said Olalekan O. Oluwole, MBBS, MD, MPH, Associate Professor of Medicine, Hematology/Oncology at Vanderbilt University and primary investigator for the study. “Additionally, the duration of response and survival benefits were demonstrated regardless of the patients’ subsequent allogeneic stem cell transplant status.”

In the poster being presented, patients treated with the pivotal dose of Tecartus in the pooled analysis Phase 1 and 2 (n=78), the median follow-up time was 53.6 months (range 44.7-82.3) with 4-year minimum follow-up. Among all treated patients, the median OS was 25.6 months, and 47 months in patients with complete remission or complete remission with incomplete hematologic recovery (n=57), the primary endpoint. In patients <26 years (n=15), median OS (95% CI) was 23.2 months (9.0-NE) and was 26.0 months (15.9-NE) in patients ≥26 years (n=63), OS was a key secondary endpoint. Median OS (95% CI) in patients with one prior therapy (n=15) was 60.4 months (7.6-NE) and was 25.4 months (15.9-47.0) in patients with ≥2 prior therapies (n=63).

Medians for OS (95% CI) in patients with (n=38) and without (n=40) prior blinatumomab were 15.9 (8.3-26.0) and 60.4 months (18.6-NE), respectively (unbalanced patient characteristics and small numbers limit interpretation of these results). Median OS (95% CI) was 36.3 months (10.2-NE) in responders who went on to subsequent allogeneic stem cell transplant (n=14) and 60.4 months (23.2-NE) in those who did not (n=43). No new adverse events or deaths occurred since the three-year analysis. Rates of infection were Grade ≥3 and higher in patients over 26 years and in patients with prior blinatumomab.

“We are pleased that Tecartus continues to demonstrate improved survival outcomes after four years of follow-up in adult patients who would otherwise have very few treatment options,” said Ibrahim Elhoussieny, MD, Vice President, Medical Affairs, Kite. “Notably, Tecartus numerically improved overall survival particularly for patients when given in earlier lines of therapy, and is an important treatment option for the large portion of adult B-ALL patients who relapse or are refractory to other treatments. We look forward to continuing to improve survival in more people with this challenging blood cancer.”

About ZUMA-3

ZUMA-3 is an ongoing international multicenter (US, Canada, Europe), single arm, open label, registrational Phase 1/2 study of Tecartus in adult patients (≥18 years old) with ALL whose disease is refractory to or has relapsed following standard systemic therapy or hematopoietic stem cell transplantation. The primary endpoint is the rate of overall complete remission or complete remission with incomplete hematological recovery by central assessment. Duration of remission and relapse-free survival, overall survival, minimal residual disease (MRD) negativity rate, and alloSCT rate were assessed as secondary endpoints.

About Acute Lymphoblastic Leukemia

ALL is an aggressive and rare type of blood cancer that can also involve the lymph nodes, spleen, liver, central nervous system and other organs. While 80% of ALL occurs in children, it represents a devastating disease in adults. In adults, B-cell precursor ALL is the most common form, accounting for 75% of cases. Survival rates in adults with R/R B-ALL are poor, with median OS at less than eight months.

About Tecartus

Please see full FDA Prescribing Information, including BOXED WARNING and Medication Guide. Tecartus is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of:

Adult patients with relapsed or refractory mantle cell lymphoma (MCL).
This indication is approved under accelerated approval based on overall response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
Adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).
https://www.tecartus.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 supply and commercial product manufacturing.

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.

Kite, the Kite logo, Tecartus, and GILEAD are trademarks of Gilead Sciences, Inc., or its related companies.

For more information about Kite, please visit the company’s website at www.kitepharma.com or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000. Follow Kite on social media on X ( @KitePharma ) and LinkedIn .

Source: Gilead Sciences, Inc.

Gilead Sciences, Inc. (GILD) Stock,

https://www.gilead.com/

https://www.tecartus.com/

Approved Uses TECARTUS® is a treatment for adults with mantle cell lymphoma or acute lymphoblastic leukemia. It is used following disease progression while on or after other treatment. TECARTUS is different than other cancer medicines because it is made from your own white blood cells, which have been modified to recognize and attack your lymphoma cells.

YESCARTA® (axicabtagene ciloleucel) suspension for intravenous infusion

June 03, 2024

Encouraging New Data Presented on Kite’s Yescarta® for Relapsed/Refractory Central Nervous System Lymphoma

-- At Median Follow-Up of 24.2 Months, No Additional Risks of Adverse Events Related to Yescarta Were Observed --

-- Findings Also Suggest Efficacy Trend with Median Progression-Free Survival and Durability of Response of More Than a Year --

-- Data Presented Orally at the 2024 American Society of Clinical Oncology Annual Meeting --

SANTA MONICA, Calif.--(BUSINESS WIRE)-- Kite, a Gilead Company (Nasdaq: GILD), announced data from a pilot study in collaboration with Dana-Farber Cancer Institute that demonstrate Yescarta® (axicabtagene ciloleucel) is well-tolerated in patients living with relapsed or refractory (R/R) primary or secondary central nervous system lymphoma (PCNSL and SCNSL). The findings, which also suggest a trend in efficacy, were presented today in an oral session (Abstract #2006) at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting.

Central nervous system lymphoma (CNSL) is an aggressive and rare form of non-Hodgkin lymphoma that has either originated in (primary) or spread to (secondary) the brain, eye, spinal cord or cerebrospinal fluid. The prognosis of PCNSL has historically been poor with a five-year survival rate of only 30%. More than half of the patients experience a relapse after front-line treatment, with a median survival of approximately two months. R/R CNSL is considered an area of unmet clinical need with no standard of care treatment options.

“Patients with central nervous system involvement of large B-cell lymphoma were excluded from the studies that led to the FDA approval of axi-cel in relapsed/refractory large B-cell lymphoma,” said Lakshmi Nayak, MD, Associate Professor of Neurology, Harvard Medical School and Director of the Center for CNS Lymphoma, Dana-Farber Cancer Institute. “We conducted this pilot study to evaluate the safety of axi-cel in CNSL patients and to see if there would be a preliminary signal of efficacy. Not only did we see a high response rate with axi-cel in this heavily pre-treated population, but importantly they were durable. While we need more data to evaluate axi-cel in a larger study, these results are promising and represent a potential breakthrough in the treatment of this particularly rare and aggressive brain cancer for which there are limited options when it recurs.”

In this pilot study of 18 patients with CNSL, at a median follow-up of 24.2 months, no treatment-limiting toxicities and no apparent additional risk of adverse events were reported. Immune effector cell-associated neurologic syndrome (ICANS) was observed among 44% of patients (27.8% Grade >3).

The objective response rate was 94.4% and the complete response rate was 66.7%. The median time to best response was three months. The median duration of response was 13.4 months and 9 patients had progressed. At a median follow-up of 24 months, the median progression-free survival was 14.3 months (95% CI: 6.3-NR) and median overall survival was 26.4 months (95% CI: 11.2-NR).

Ninety percent of patients developed grade 1 or 2 cytokine release syndrome; two patients developed Ommaya-related meningitis requiring explant with subsequent recovery. One patient developed grade 3 electrographic focal status epilepticus that resolved with anti-epileptic agents. Seven patients have died, all from disease progression.

“We are very encouraged by the data presented today that indicate the potential to extend the benefits of Yescarta to people with relapsed/refractory primary and secondary central nervous system lymphoma, whose prognoses are typically very poor,” said Ibrahim Elhoussieny, MD, Vice President, Medical Affairs, Kite. “These early data support that CAR T-cell therapy may potentially offer a treatment option to these patients.”

The Yescarta U.S. Prescribing Information has a BOXED WARNING for the risks of CRS and neurologic toxicities, and Yescarta is approved with a Risk Evaluation and Mitigation Strategy (REMS) due to these risks; see below for Important Safety Information.

About Central Nervous System Lymphoma

Central nervous system lymphoma (CNSL) is an aggressive and rare form of non-Hodgkin lymphoma that has either originated in (primary) or spread (secondary) to the brain, eye, spinal cord or cerebral spinal fluid. The prognosis of PCNSL has historically been poor with a five-year survival rate of only 30%. More than half of the patients experience a relapse, after which the average survival is approximately two months. R/R CNSL is considered an area of unmet clinical need with no standard of care treatment options.

There is an estimated annual incidence of 1,500 cases of primary CNSL in the United States. Primary CNS comprises 3% of all primary brain tumors and 1% of all cases of non-Hodgkin lymphoma. CNSL is most likely to be seen in the elderly and people with a compromised immune system.

About the Study

The pilot study enrolled 18 patients (13 PCNSL, 4 SCNSL, 1 concurrent systemic and ocular lymphoma), of whom the first six patients were observed for treatment-limiting toxicities (TLTs). The primary endpoint was safety, measured by rate of TLTs and grade 3+ adverse events (AEs). Secondary endpoints included objective response rate, complete response rate, duration of response, progression-free survival and overall survival (OS).

About Yescarta

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

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

Adult patients with large B-cell lymphoma that is refractory to first-line chemoimmunotherapy or that relapses within 12 months of first-line chemoimmunotherapy.
Adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma, and DLBCL arising from follicular lymphoma.

Limitations of Use: YESCARTA is not indicated for the treatment of patients with primary central nervous system lymphoma.

Adult patients with relapsed or refractory follicular lymphoma (FL) after two or more lines of systemic therapy. This indication is approved under accelerated approval based on the response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trial(s).
https://www.yescarta.com/

About Kite

About Gilead Sciences

Kite, the Kite logo, Yescarta, and GILEAD are trademarks of Gilead Sciences, Inc. or its related companies.

For more information on Kite, please visit the company’s website at www.kitepharma.com . Follow Kite on social media on X ( @KitePharma ) and LinkedIn .

Source: Gilead Sciences, Inc.

Gilead Sciences, Inc. (GILD) Stock,

https://www.gilead.com/

https://www.yescarta.com/

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

ENHERTU® (trastuzumab deruxtecan)

Enhertu demonstrated a median progression-free survival of 13.2 months in HR-positive, HER2-low and HER2-ultralow metastatic breast cancer following one or more lines of endocrine therapy

PUBLISHED2 June 2024

DESTINY-Breast06 results show AstraZeneca and Daiichi Sankyo’s Enhertu is the first HER2-directed medicine and ADC to demonstrate clinically meaningful benefit for patients in this setting

Additionally, data from DESTINY-Breast03 and DESTINY-Breast07 trials in HER2-positive metastatic breast cancer reinforce Enhertu as standard of care in 2nd-line setting and highlight potential in 1st-line setting

Detailed positive results from the DESTINY-Breast06 Phase III trial showed that Enhertu (trastuzumab deruxtecan) demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared to standard-of-care chemotherapy in patients with HR-positive, HER2-low (IHC 1+ or 2+/ISH-) metastatic breast cancer and the overall trial population (patients with HR-positive, HER2-low and HER2-ultralow [defined as IHC 0 with membrane staining] expression) following one or more lines of endocrine therapy.

These results will be presented today as a late-breaking oral presentation during the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting (abstract #LBA1000).

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

In the primary analysis of DESTINY-Breast06, results showed Enhertu reduced the risk of disease progression or death by 38% by blinded independent central review (BICR) versus chemotherapy in patients with HER2-low expression (hazard ratio [HR] 0.62; 95% confidence interval [CI]: 0.51-0.74; p<0.0001). Median PFS was 13.2 months in the Enhertu arm compared to 8.1 months for chemotherapy.

PFS results by BICR in the overall trial population were similar and showed Enhertu achieved a 37% reduction in the risk of disease progression or death compared to chemotherapy, with a median PFS of 13.2 months with Enhertu versus 8.1 months for chemotherapy (HR 0.63; 95% CI: 0.53-0.75; p<0.0001).

A prespecified exploratory analysis showed the clinically meaningful improvement in PFS was consistent between patients with HER2-low and HER2-ultralow expression. In patients with HER2-ultralow expression, Enhertu reduced the risk of disease progression or death by 22% compared to chemotherapy with a median PFS of 13.2 months versus 8.3 months, respectively (HR 0.78; 95% CI: 0.50-1.21).

Giuseppe Curigliano, MD, PhD, Professor of Medical Oncology at the University of Milan and Head of the Division of Early Drug Development at the European Institute of Oncology, IRCCS, Italy and principal investigator for the trial, said: “Endocrine therapies are widely used early in the treatment of HR-positive metastatic breast cancer, but following one or more lines of treatment, patients often derive limited efficacy from further endocrine-based therapy. With a median progression-free survival of more than a year, the results from DESTINY-Breast06 show that Enhertu could become a new standard of care for patients with HER2-low- and HER2-ultralow-expressing tumours following endocrine therapy in the metastatic setting.”

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “DESTINY-Breast06 represents another potential paradigm shift in how we treat patients across the spectrum of HR-positive metastatic breast cancer. The results reinforce the potential for Enhertu to improve outcomes earlier in the treatment landscape and in a broader population of patients with HER2-expressing breast cancer who have never before been eligible for a HER2-directed therapy.”

Ken Takeshita, Global Head, R&D, Daiichi Sankyo, said: “Enhertu continues to deliver pioneering results for a HER2-directed medicine across many different types of cancer. These latest results from DESTINY-Breast06 demonstrate clinically meaningful results with Enhertu even in tumours with very low levels of HER2 expression, suggesting that it may have an important role in treating a wide range of HER2-expressing metastatic breast cancer.”

In patients with HER2-low expression, confirmed objective response rate (ORR) was 56.5% for Enhertu versus 32.2% with chemotherapy. In the overall trial population, confirmed ORR was 57.3% for Enhertu versus 31.2% with chemotherapy and in patients with HER2-ultralow expression the confirmed ORR was 61.8% versus 26.3%, respectively. Complete responses were seen in 13 patients from the Enhertu arm, including nine patients with HER2-low expression. In the HER2-ultralow subgroup, four patients in the Enhertu arm had complete responses. No complete responses were seen in the chemotherapy arm.

Additional Enhertu data at ASCO

DESTINY-Breast03 updated results
Updated overall survival (OS) results from the DESTINY-Breast03 Phase III trial showed Enhertu continued to demonstrate a clinically meaningful survival improvement over trastuzumab emtansine (T-DM1) after more than three years of follow up in patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with trastuzumab.

Results showed median OS was 52.6 months in the Enhertu arm compared to 42.7 months for T-DM1 (HR 0.73; 95% CI: 0.56-0.94).

The safety profile of Enhertu continues to be generally manageable and no cumulative toxicities were observed with longer follow-up. Results will be presented during the 2024 ASCO Annual Meeting (abstract #1025).

DESTINY-Breast07 results
Interim results from the DESTINY-Breast07 Phase Ib/II trial of Enhertu alone or in combination with other anticancer therapies as a 1st-line treatment for HER2-positive metastatic breast cancer demonstrated promising clinical activity for Enhertu as a monotherapy (n=75) and in combination with pertuzumab (n=50). Results were presented as an oral presentation at the 2024 ASCO Annual Meeting (abstract #1009).

Results showed a confirmed ORR of 76.0% with Enhertu and 84.0% with Enhertu in combination with pertuzumab. The 12-month PFS rate was 80.8% with Enhertu monotherapy and 89.4% with Enhertu and pertuzumab.

The safety of Enhertu as a monotherapy and in combination with pertuzumab was consistent with the known safety profiles of each therapy. ILD/pneumonitis was reported in seven patients (9.3%) in the Enhertu monotherapy arm and seven patients (14.0%) in the combination arm. All ILD events were Grade 3 or lower.

These are the first data presented for Enhertu as a 1st-line treatment in HER2-positive metastatic breast cancer. Analyses from the ongoing DESTINY-Breast09 Phase III trial will provide further insights regarding the efficacy and safety of Enhertu in this HER2-positive patient population.

Notes

Breast cancer and HER2 expression
Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths worldwide.1 More than two million breast cancer cases were diagnosed in 2022 with more than 665,000 deaths globally.1 While survival rates are high for those diagnosed with early breast cancer, only approximately 30% of patients who are diagnosed with or who progress to metastatic disease are expected to live five years after their diagnosis.2

HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumours, including breast cancer.3 Patients with high levels of HER2 expression (IHC 3+ or 2+/ISH+) are classified as HER2-positive and treated with HER2-directed therapies, representing approximately 15-20% of all breast cancers.4 Historically, tumours that were not classified as HER2-positive were classified as HER2-negative.5

HR-positive, HER2-negative is the most common breast cancer subtype, accounting for approximately 70% of all breast cancers.2 Despite being classified as HER2-negative, many of these tumours still carry some level of HER2 expression.5 It is estimated that approximately 60-65% of HR-positive, HER2-negative breast cancers are HER2-low and potentially an additional 25% may be HER2-ultralow.6,7

Endocrine therapies are widely used in the early lines of treatment for HR-positive metastatic breast cancer; however, after two lines of treatment, further efficacy from endocrine therapy is often limited.8 The current standard of care following endocrine therapy is chemotherapy, which is associated with poor response rates and outcomes.8-11

Prior to the approval of Enhertu in HER2-low metastatic breast cancer post chemotherapy based on the DESTINY-Breast04 trial, there were no targeted therapies approved specifically for patients with HER2-low expression. There are no targeted therapies specifically approved for patients with HER2-low expression prior to chemotherapy or for patients with HER2-ultralow expression.12

DESTINY-Breast06
DESTINY-Breast06 is a global, randomised, open-label, Phase III trial evaluating the efficacy and safety of Enhertu (5.4 mg/kg) versus investigator’s choice of chemotherapy (capecitabine, paclitaxel or nab-paclitaxel) in patients with HR-positive, HER2-low (IHC 1+ or 2+/ISH-) or HER2-ultralow (defined as IHC 0 with membrane staining) advanced or metastatic breast cancer. Patients in the trial had no prior chemotherapy for advanced or metastatic disease and received at least two lines of prior endocrine therapy in the metastatic setting. Patients were also eligible if they had received one prior line of endocrine therapy combined with a CDK4/6 inhibitor in the metastatic setting and experienced disease progression within six months of starting 1st-line treatment or received endocrine therapy as an adjuvant treatment and experienced disease recurrence within 24 months.

The primary endpoint is PFS in the HR-positive, HER2-low patient population as measured by BICR. Key secondary endpoints include PFS by BICR in the overall trial population (HER2-low and HER2-ultralow), OS in the HER2-low patient population and OS in the overall trial population. Other secondary endpoints include ORR, DOR, time to first subsequent treatment or death, time to second subsequent treatment or death and safety.

DESTINY-Breast06 enrolled 866 patients (n=713 for HER2-low and n=153 for HER2-ultralow) randomised at multiple sites in Asia, Europe, Australia, North America and South America. For more information about the trial, visit ClinicalTrials.gov.

DESTINY-Breast03
DESTINY-Breast03 is a global, head-to-head, randomised, open-label, pivotal Phase III trial evaluating the efficacy and safety of Enhertu (5.4 mg/kg) versus T-DM1 in patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane. The primary efficacy endpoint of DESTINY-Breast03 is PFS based on BICR. OS is the key secondary efficacy outcome measure. Other secondary endpoints include ORR, DOR, PFS based on investigator assessment and safety.

DESTINY-Breast03 enrolled 524 patients at multiple sites in Asia, Europe, North America, Australia and South America. Primary results from DESTINY-Breast03 were published in The New England Journal of Medicine, with updated OS results published in The Lancet. For more information about the trial, visit ClinicalTrials.gov.

DESTINY-Breast07
DESTINY-Breast07 is a global, randomised, open-label Phase Ib/II dose-finding and dose-expansion trial to explore the safety, tolerability and anti-tumour activity of Enhertu alone or in combination with other anticancer agents in patients with HER2-positive metastatic breast cancer.

The study consists of two phases: a dose escalation phase and a dose expansion phase. The dose escalation phase enrolled patients with locally assessed HER2-positive or advanced metastatic breast cancer in 2nd-line or later treatment. The dose expansion phase enrolled patients with previously untreated for HER2-positive advanced or metastatic breast cancer.

The primary endpoints of DESTINY-Breast07 are safety and tolerability. Secondary endpoints include ORR and PFS based on investigator assessment.

DESTINY-Breast07 enrolled 244 patients at multiple sites in Asia, Europe, North America and South 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 number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

Enhertu (5.4 mg/kg) is approved in more than 60 countries for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+ or in-situ hybridisation [ISH]+) 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 (5.4 mg/kg) is approved in more than 60 countries for the treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or 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 from the DESTINY-Breast04 trial.

Enhertu (5.4 mg/kg) is approved in more than 35 countries for the treatment of adult patients with unresectable or metastatic NSCLC whose tumours have activating HER2 (ERBB2) mutations, as detected by a locally or regionally approved test, and who have received a prior systemic therapy based on the results from the DESTINY-Lung02 trial. Continued approval in the US for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Enhertu (6.4 mg/kg) is approved in more than 40 countries for the treatment of adult patients with locally advanced or metastatic HER2-positive (IHC 3+ or 2+/ISH+) gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 and/or DESTINY-Gastric02 trials.

Enhertu (5.4 mg/kg) is approved in the US for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumours who have received prior systemic treatment and who have no satisfactory alternative treatment options based on results from the DESTINY-PanTumor02, DESTINY-Lung01 and DESTINY-CRC02 trials.

https://enhertu.com/en/breast

Enhertu development programme
A comprehensive global clinical development programme is underway evaluating the efficacy and safety of Enhertu monotherapy across multiple HER2-targetable cancers. Trials in combination with other anti-cancer treatments, such as immunotherapy, also are underway.

Daiichi Sankyo collaboration
AstraZeneca and Daiichi Sankyo entered into a global collaboration to jointly develop and commercialise Enhertu in March 2019 and datopotamab deruxtecan in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is responsible for the manufacturing and supply of Enhertu and datopotamab deruxtecan.

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 antibody drug conjugate (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 and Zoladex (goserelin) and aims to reshape the HR-positive space with first-in-class AKT inhibitor, Truqap, and next-generation SERD and potential new medicine camizestrant. 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 patients 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), Truqap in combination with chemotherapy, and Imfinzi in combination with other oncology medicines, including Lynparza and Enhertu.

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 social media @AstraZeneca.

ENHERTU® Demonstrated a Median Progression-Free Survival of 13.2 Months in HR Positive, HER2 Low and HER2 Ultralow Metastatic Breast Cancer Following One or More Lines of Endocrine Therapy

Jun. 02, 2024 8:00 AM ET

AstraZeneca PLC (AZN), DSNKY

DESTINY-Breast06 results show Daiichi Sankyo and AstraZeneca’s ENHERTU is the first HER2 directed medicine and antibody drug conjugate to demonstrate clinically meaningful benefit for patients in this setting
Additionally, data from DESTINY-Breast03 and DESTINY-Breast07 trials in HER2 positive metastatic breast cancer reinforce ENHERTU as standard of care in second-line setting and highlight potential in first-line setting

TOKYO & BASKING RIDGE, N.J.--(BUSINESS WIRE)--

https://seekingalpha.com/pr/19744753-enhertu-demonstrated-median-progression-free-survival-of-13_2-months-in-hr-positive-her2-low?hasComeFromMpArticle=false

AstraZeneca PLC (AZN), DSNKY

https://www.astrazeneca.com/

https://enhertu.com/en/breast

biotecMAX™ 2024 Insight

Imfinzi (durvalumab)

Imfinzi is first and only immunotherapy to show survival benefit in limited-stage small cell lung cancer in global Phase III trial, reducing the risk of death by 27% vs. placebo

PUBLISHED2 June 2024

57% of patients treated with Imfinzi were alive at three years in ADRIATIC Phase III trial

Positive results from the ADRIATIC Phase III trial showed AstraZeneca’s Imfinzi (durvalumab) demonstrated statistically significant and clinically meaningful improvements in the dual primary endpoints of overall survival (OS) and progression-free survival (PFS) compared to placebo for patients with limited-stage small cell lung cancer (LS-SCLC) who had not progressed following standard-of-care concurrent chemoradiotherapy (cCRT).

These results will be presented today during the Plenary Session at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting (abstract #LBA5).

Results from the planned interim analysis showed Imfinzi reduced the risk of death by 27% versus placebo (based on an OS hazard ratio [HR] of 0.73; 95% confidence interval [CI] 0.57-0.93; p=0.0104). Estimated median OS was 55.9 months for Imfinzi versus 33.4 months for placebo. An estimated 57% of patients treated with Imfinzi were alive at three years compared to 48% on placebo. Imfinzi also reduced the risk of disease progression or death by 24% (based on a PFS HR of 0.76; 95% CI 0.61-0.95; p=0.0161) versus placebo. Median PFS was 16.6 months for Imfinzi versus 9.2 months for placebo. An estimated 46% of patients treated with Imfinzi had not experienced disease progression at two years compared to 34% on placebo.

The OS and PFS benefits observed were generally consistent across key prespecified patient subgroups including age, sex, race, disease stage1 at diagnosis, prior radiation and whether patients received prophylactic cranial irradiation.

David R. Spigel, MD, Chief Scientific Officer at Sarah Cannon Research Institute and investigator in the trial, said: “The ADRIATIC results represent a breakthrough in limited-stage small cell lung cancer, a highly aggressive disease where recurrence rates are high and only 15 to 30 per cent of patients survive five years. Durvalumab is the first systemic treatment to show improved survival for these patients in decades and should become a new standard of care in this setting.”

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “The strong improvement in overall survival seen with Imfinzi after concurrent chemoradiotherapy is transformative in the treatment of limited-stage small cell lung cancer. These tremendous results underscore our ambition to drive up survival rates in this earlier-stage lung cancer setting, and we look forward to working with regulatory authorities to bring Imfinzi to these patients as quickly as possible.”

Notes

Small cell lung cancer
Lung cancer is the leading cause of cancer death among men and women and accounts for about one-fifth of all cancer deaths.2 Lung cancer is broadly split into non-small cell lung cancer and SCLC, with about 15% of cases classified as SCLC, a highly aggressive form of the disease.3-4

LS-SCLC (Stage I-III), which accounts for approximately 30% of SCLC diagnoses, is classified as SCLC that is generally only in one lung or one side of the chest.5-6 LS-SCLC typically recurs and progresses rapidly despite initial response to standard-of-care chemotherapy and radiotherapy.4,7 The prognosis for LS-SCLC is particularly poor, as only 15-30% of patients will be alive five years after diagnosis.8

ADRIATIC
The ADRIATIC trial is a randomised, double-blind, placebo-controlled, multi-centre global Phase III trial evaluating Imfinzi monotherapy and Imfinzi plus Imjudo (tremelimumab) versus placebo in the treatment of 730 patients with LS-SCLC who had not progressed following cCRT. In the experimental arms, patients were randomised to receive a 1500mg fixed dose of Imfinzi with or without Imjudo 75mg every four weeks for up to four doses/cycles each, followed by Imfinzi every four weeks for up to 24 months.

The dual primary endpoints were PFS and OS for Imfinzi monotherapy versus placebo. Key secondary endpoints included OS and PFS for Imfinzi plus Imjudo versus placebo, safety and quality of life measures. The trial included 164 centres in 19 countries across North and South America, Europe and Asia.

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 currently approved in a number of countries across multiple types of lung cancer. Imfinzi is the only approved immunotherapy and the global standard of care in the curative-intent setting of unresectable, Stage III non-small cell lung cancer (NSCLC) in patients whose disease has not progressed after chemoradiation therapy. Imfinzi is also approved for the treatment of extensive-stage SCLC and in combination with a short course of Imjudo and chemotherapy for the treatment of metastatic NSCLC.

In addition to its indications in lung cancers, Imfinzi is approved in a number of countries in combination with chemotherapy (gemcitabine plus cisplatin) in locally advanced or metastatic biliary tract cancer and in combination with Imjudo in unresectable hepatocellular carcinoma (HCC). Imfinzi is also approved as a monotherapy in unresectable HCC in Japan and the EU and in previously treated patients with advanced bladder cancer in a small number of countries.

https://www.imfinzi.com/

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 (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 strives to redefine cancer care and help transform outcomes for patients with Imfinzi as a monotherapy and in combination with Imjudo as well as other novel immunotherapies and modalities. The Company is also investigating next-generation immunotherapies like bispecific antibodies and therapeutics that harness different aspects of immunity to target cancer, including cell therapy and T cell engagers.

AstraZeneca is 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. The Company is focused on exploring novel combination approaches to help prevent treatment resistance and drive longer immune responses. 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 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 social media @AstraZeneca.

IMFINZI® (durvalumab) is the first and only immunotherapy to show survival benefit in limited-stage small cell lung cancer in global Phase III trial, reducing the risk of death by 27% vs. placebo

Jun. 02, 2024 8:05 AM ET

AstraZeneca PLC (AZN)

57% of patients treated with IMFINZI were alive at three years in ADRIATIC Phase III trial

WILMINGTON, Del.--(BUSINESS WIRE)

https://seekingalpha.com/pr/19744760-imfinzi-durvalumab-is-first-and-only-immunotherapy-to-show-survival-benefit-in-limited-stage?hasComeFromMpArticle=false

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Tagrisso (osimertinib)

Tagrisso with the addition of chemotherapy recommended for approval in the EU by CHMP for patients with EGFR-mutated advanced lung cancer

PUBLISHED3 June 2024

Recommendation based on FLAURA2 results which showed Tagrisso plus
chemotherapy extended median progression-free survival by nearly 9 months vs.
standard of care

AstraZeneca’s Tagrisso (osimertinib) with the addition of pemetrexed and platinum-based chemotherapy has been recommended for approval in the European Union (EU) for 1st-line treatment of adult patients with locally advanced or metastatic epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC) whose tumours have exon 19 deletions or exon 21 (L858R) mutations.

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) based its positive opinion on the results from the FLAURA2 Phase III trial, which were also published in The New England Journal of Medicine.

Results showed Tagrisso with the addition of chemotherapy reduced the risk of disease progression or death by 38% compared to Tagrisso monotherapy, which is the 1st-line global standard of care (hazard ratio [HR] 0.62; 95% confidence interval [CI] 0.49-0.79; p<0.0001). Median progression-free survival (PFS) by investigator assessment was 25.5 months for patients treated with Tagrisso plus chemotherapy, an 8.8-month improvement versus Tagrisso monotherapy (16.7 months).

While overall survival (OS) remained immature at the second interim analysis (41% maturity), an encouraging trend towards an OS benefit was observed with Tagrisso plus chemotherapy versus Tagrisso alone (HR 0.75; 95% CI 0.57-0.97). The trial continues to assess OS as a key secondary endpoint.

Each year in Europe, there are more than 450,000 people diagnosed with lung cancer.1 Among those with NSCLC, the most common form of lung cancer, about 10-15% of patients in Europe have tumours with an EGFR mutation.2,3 Additionally, the majority of patients with NSCLC are diagnosed with advanced disease.4

David Planchard, MD, PhD, thoracic oncologist at Gustave Roussy Institute of Oncology and principal investigator for the trial, said: “The FLAURA2 results build on the established efficacy of osimertinib monotherapy in patients with EGFR-mutated lung cancer, demonstrating a meaningful nine-month improvement in progression-free survival with the addition of chemotherapy. Today’s positive recommendation is a vital step towards providing patients in Europe with an additional treatment option capable of extending the time before their disease progresses. This expands on the already approved use of osimertinib as monotherapy, providing physicians with options to tailor treatments that best suit their patients' specific disease needs.”

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “Today’s news reinforces the importance of Tagrisso as the backbone therapy in EGFR-mutated lung cancer. If approved in Europe, patients will have the option to be treated with Tagrisso alone, or with chemotherapy, which is especially important when caring for patients whose disease has spread to the brain or those with L858R mutations.”

The safety profile of Tagrisso plus chemotherapy was generally manageable and consistent with the established profiles of the individual medicines. Adverse event (AE) rates were higher in the Tagrisso plus chemotherapy arm, driven by well-characterised chemotherapy-related AEs. Discontinuation rates of Tagrisso due to AEs were 11% for Tagrisso plus chemotherapy and 6% for monotherapy.

Tagrisso is approved as monotherapy in more than 100 countries including in the US, EU, China and Japan. Approved indications include for 1st-line treatment of patients with locally advanced or metastatic EGFRm NSCLC, locally advanced or metastatic EGFR T790M mutation-positive NSCLC, and adjuvant treatment of early-stage EGFRm NSCLC. Tagrisso with the addition of chemotherapy is also approved in the US and several other countries for the 1st-line treatment of patients with locally advanced or metastatic EGFRm NSCLC.

Notes

Lung cancer
Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-fifth of all cancer deaths.5 Lung cancer is broadly split into NSCLC and small cell lung cancer.3 Each year there are an estimated 2.4 million people diagnosed with lung cancer globally, with 80-85% of patients diagnosed with NSCLC, the most common form of lung cancer.3,5-6 The majority of all NSCLC patients are diagnosed with advanced disease.7

Approximately 10-15% of NSCLC patients in the US and Europe, and 30-40% of patients in Asia have EGFRm NSCLC.8-10 Patients with EGFRm NSCLC are particularly sensitive to treatment with an EGFR-tyrosine kinase inhibitor (EGFR-TKI) which blocks the cell-signalling pathways that drive the growth of tumour cells.11

FLAURA2
FLAURA2 is a randomised, open-label, multi-centre, global Phase III trial in the 1st-line treatment of patients with locally advanced (Stage IIIB-IIIC) or metastatic (Stage IV) EGFRm NSCLC. Patients were treated with Tagrisso 80mg once-daily oral tablets with the addition of chemotherapy (pemetrexed (500mg/m2) plus cisplatin (75mg/m2) or carboplatin (AUC5)) every three weeks for four cycles, followed by Tagrisso with pemetrexed maintenance every three weeks.

The trial enrolled 557 patients in more than 150 centres across more than 20 countries, including in the US, Europe, South America and Asia. The primary endpoint is PFS. The trial is ongoing and will continue to assess the secondary endpoint of OS.

https://www.tagrisso.com/

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 social media @AstraZeneca.

TAGRISSO® (osimertinib) reduced the risk of disease progression or death by 84% in patients with unresectable, Stage III EGFR-mutated lung cancer vs. placebo in LAURA Phase III trial

Jun. 02, 2024 2:32 PM ET

AstraZeneca PLC (AZN)
https://seekingalpha.com/pr/19744816-tagrisso-osimertinib-reduced-risk-of-disease-progression-death-84-percent-in-patients?hasComeFromMpArticle=false

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Tagrisso with the addition of chemotherapy recommended for approval in the EU by CHMP for patients with EGFR-mutated advanced lung cancer03 June 2024

Jemperli (dostarlimab)

03 June 2024 Issued: London, UK For media and investors only

Jemperli (dostarlimab) trial continues to show unprecedented results with no evidence of disease in 100% of patients with locally advanced mismatch repair deficient (dMMR) rectal cancer

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Updated analysis from Memorial Sloan Kettering Cancer Center presented at ASCO 2024 has expanded to 42 patients with clinical complete response
New treatment options are needed for patients facing negative impacts to quality-of-life with current standard of care
Additional registrational studies of dostarlimab in dMMR/microsatellite instability-high rectal (MSI-H) and colorectal cancer are recruiting

GSK plc (LSE/NYSE: GSK) today announced updated, longer-term results from the phase II supported collaborative study with Memorial Sloan Kettering Cancer Center (MSK) evaluating Jemperli (dostarlimab) as a first-line treatment—as an alternative to surgery—for mismatch repair deficient (dMMR) locally advanced rectal cancer. The trial showed an unprecedented 100% clinical complete response rate (cCR) in 42 patients who completed treatment with dostarlimab, defined as complete pathologic response or no evidence of tumours as assessed by magnetic resonance imaging, endoscopy and digital rectal exam. In the first 24 patients evaluated, a sustained clinical complete response with a median follow-up of 26.3 months (95% CI: 12.4-50.5) was observed.

These late-breaking data are being presented today at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting (31 May – 4 June) in Chicago, IL as a rapid oral presentation (abstract LBA3512). The latest research presented today from the phase II trial builds on the findings initially presented in a late-breaking presentation at the 2022 ASCO Annual Meeting with simultaneous publication in The New England Journal of Medicine.1

Hesham Abdullah, Senior Vice President, Global Head Oncology, R&D, GSK, said: “The data showing no evidence of disease in 42 patients is remarkable. These results bring us one step closer to understanding the potential of dostarlimab in this curative-intent setting for patients with dMMR locally advanced rectal cancer. We look forward to evaluating dostarlimab in certain colorectal cancers in our ongoing AZUR-1 and AZUR-2 registrational studies.”

The current standard-of-care (SoC) for patients with dMMR/microsatellite instability-high (MSI-H) locally advanced rectal cancer is initial treatment with chemotherapy plus radiation followed by surgery to remove the tumour along with portions of the intestine and/or surrounding tissue.1 This results in initial positive outcomes for most patients, but nearly one-third ultimately die from cancer that has spread to other parts of the body (distant metastasis).2 Additionally, the surgery and chemoradiotherapy associated with SoC can lead to long-term adverse effects that have a significantly negative impact on quality of life, including bowel, urinary and sexual dysfunction, secondary cancers and infertility.1

Andrea Cercek, MD, Section Head of Colorectal Cancer and Co-Director of the Center for Young Onset Colorectal and Gastrointestinal Cancer, MSK, and Principal Investigator of the phase II study said: “These findings demonstrate the potential of dostarlimab as a novel approach to treating locally advanced dMMR rectal cancer that leads to durable complete tumour regression without the need for life-altering treatment. As a clinician, I’ve seen firsthand the debilitating impact of standard treatment of dMMR rectal cancer and am thrilled about the potential of dostarlimab in these patients.”

The safety and tolerability profile of dostarlimab was generally consistent with the known safety profile of the agent. No adverse events of grade 3 or higher were reported in this trial.

Dostarlimab is not approved anywhere in the world for the frontline treatment of locally advanced dMMR rectal cancer. GSK is advancing studies evaluating dostarlimab in patients with advanced/metastatic stages of dMMR/MSI-H colorectal cancer through its AZUR clinical trial programme. AZUR-1 is a global, multi-centre, open-label, phase II registrational clinical trial investigating the efficacy and safety of dostarlimab as monotherapy – as a replacement for chemotherapy, radiation and/or surgery – for treatment-naïve patients with dMMR/MSI-H locally advanced rectal cancer. The AZUR-1 trial aims to confirm the findings of the supported collaborative study in locally advanced dMMR rectal cancer led by Dr. Cercek at MSK. AZUR-2 is a phase III trial evaluating the efficacy of perioperative dostarlimab compared with SoC in participants with untreated T4N0 or Stage III (resectable) dMMR/MSI-H colon cancer.

About dMMR/MSI-H rectal cancer

Rectal cancer is a form of cancer that starts in the rectum, the final section of the large intestine, and is often categorised as part of a group of cancers called colorectal cancer.3 Colorectal cancer is the third most commonly diagnosed cancer in the world.4 In the US, it is estimated that approximately 46,220 individuals are diagnosed annually with rectal cancer.5 Approximately 5-10% of all rectal cancers are mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H), meaning that they contain abnormalities that affect the proper repair of DNA when copied in a cell.6 Mismatch repair-deficient status is a biomarker that has been shown to predict response to immune checkpoint blockade with PD-1 therapy.7,8 Tumours with this biomarker are most commonly found in endometrial, colorectal and other gastrointestinal cancers but may also be found in other solid tumours.9-12

About Jemperli (dostarlimab)

Jemperli, a programmed death receptor-1 (PD-1)-blocking antibody, is the backbone of GSK’s ongoing immuno-oncology-based research and development programme. A robust clinical trial programme includes studies of Jemperli alone and in combination with other therapies in gynaecologic, colorectal and lung cancers, as well as where there are opportunities for transformational outcomes. It is the first and only immuno-oncology treatment approved, in combination with chemotherapy, in the frontline setting for primary advanced or recurrent dMMR/MSI-H endometrial cancer.

In the US, Jemperli is indicated in combination with carboplatin and paclitaxel, followed by Jemperli as a single agent for the treatment of adult patients with primary advanced or recurrent endometrial cancer that is dMMR, as determined by a US FDA-approved test, or MSI-H, and as a single agent for adult patients with dMMR recurrent or advanced endometrial cancer, as determined by a US FDA-approved test, that has progressed on or following a prior platinum-containing regimen in any setting and are not candidates for curative surgery or radiation. The sBLA supporting this indication in combination with carboplatin and paclitaxel for dMMR/MSI-H primary advanced or recurrent endometrial cancer received Breakthrough Therapy designation and Priority Review from the US FDA. Jemperli is also indicated in the US for patients with dMMR recurrent or advanced solid tumours, as determined by a US FDA-approved test, that have progressed on or following prior treatment and who have no satisfactory alternative treatment options. The latter indication is approved in the US under accelerated approval based on tumour response rate and durability of response. Continued approval for this indication in solid tumours may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

Jemperli was discovered by AnaptysBio, Inc. and licensed to TESARO, Inc., under a collaboration and exclusive license agreement signed in March 2014. Under this agreement, GSK is responsible for the ongoing research, development, commercialisation, and manufacturing of Jemperli, and cobolimab (GSK4069889), a TIM-3 antagonist.

Important Information for Jemperli in the EU

Indication 

Jemperli is indicated:

in combination with carboplatin-paclitaxel, for the treatment of adult patients with mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) primary advanced or recurrent endometrial cancer and who are candidates for systemic therapy;
as monotherapy for treating adult patients with mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) recurrent or advanced endometrial cancer that has progressed on or following prior treatment with a platinum-containing regimen.
https://jemperli.com/

Refer to the Jemperli EMA Reference Information for a full list of adverse events and the complete important safety information in the EU here: https://www.ema.europa.eu/en/medicines/human/EPAR/jemperli.

GSK in oncology

Oncology is an emerging therapeutic area for GSK where we are committed to maximising patient survival with a current focus on haematologic malignancies, gynaecologic cancers, and other solid tumours through breakthroughs in immuno-oncology and tumour-cell targeting therapies.

About GSK

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

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https://jemperli.com/

Approved Uses JEMPERLI is a prescription medicine used to treat adults with: a kind of uterine cancer called endometrial cancer (EC) JEMPERLI may be used in combination with the chemotherapy medicines, carboplatin and paclitaxel, and then after that JEMPERLI may be used alone: when a laboratory test shows that your tumor is mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H), and your cancer has spread outside your uterus (advanced) or, your cancer has returned. JEMPERLI may be used alone: when a laboratory test shows that your tumor is dMMR, and your cancer has returned, or it has spread (advanced EC), and you have received chemotherapy that contains platinum and it did not work or is no longer working, and your cancer cannot be treated by surgery or radiation. It is not known if JEMPERLI is safe and effective in children.

Kisqali® (ribociclib)

Latest analysis of Novartis NATALEE study shows Kisqali® reduces risk of cancer recurrence for early breast cancer patients with high-risk node-negative disease

May 31, 2024

Addition of Kisqali® (ribociclib) to endocrine therapy (ET) demonstrated a 28% risk reduction in invasive disease-free survival (iDFS) in subgroup of patients with node-negative (N0) disease at high risk of recurrence1
Patients with N0 disease are currently ineligible to receive CDK4/6 inhibitor (CDK4/6i) treatment to manage risk of recurrence; treatment with ET alone leaves them with significant unmet need2,3
Efficacy, safety and tolerability profile observed in N0 disease subgroup are consistent with the overall NATALEE study population1,2,4,5
Based on NATALEE data, the number of patients that could potentially benefit from CDK4/6i treatment to reduce their chances of cancer coming back could double; Novartis has submitted these results to FDA and EMA1,2

Basel, May 31, 2024 – Novartis is announcing results from a subgroup analysis of patients with high-risk, node-negative (N0) hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) early breast cancer (EBC) from the Phase III NATALEE trial. The latest analysis demonstrated that Kisqali® (ribociclib) plus endocrine therapy (ET), compared to ET alone, showed an improvement in rates of invasive disease-free survival (iDFS), distant recurrence-free survival (DRFS), and distant disease-free survival (DDFS) in high-risk EBC patients with N0 disease1,2. These data are being presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting today and are consistent with the significant benefits observed in the broad population of patients with stage II and III HR+/HER2- EBC in the pivotal NATALEE trial, initially presented at ASCO 20231,2.

Kisqali iDFS, DRFS and DDFS rates in key pre-specified subgroup1:

Subgroup3-year iDFS rate, %3-year DRFS rate, %3-year DDFS rate, %High-risk node-negative (N0)Kisqali + ET: 93.2
ET alone: 90.6
(HR=0.72; 95% CI: 0.41, 1.27)Kisqali + ET: 96.3
ET alone: 92.5
(HR=0.58; 95% CI: 0.29, 1.17)Kisqali + ET: 94.3
ET alone: 91.5
(HR=0.70; 95% CI: 0.38, 1.29)

“More than 1 in 3 patients diagnosed with early-stage breast cancer, regardless of nodal involvement, are at risk of experiencing recurrent disease despite treatment with standard chemotherapy and/or endocrine therapy,” said Denise A. Yardley, MD, Associate Director, Breast Cancer Research; Executive Member, Breast Cancer Research Executive Committee, Sarah Cannon Research Institute; and Principal Investigator of the NATALEE clinical trial. “Notably, the NATALEE trial has shed light on the node-negative patient population, an important at-risk subgroup that could benefit from more options to reduce their risk of their cancer returning. The findings from this trial underscore the efficacy of ribociclib in early-stage node-negative breast cancer, highlighting its role as a viable and well-tolerated treatment intervention that could significantly diminish the recurrence risk for this particular group.”

The safety profile of Kisqali at the 400 mg dose in the high-risk, N0 subgroup remains consistent with the well-tolerated profile previously demonstrated in the intent-to-treat population with generally low-grade adverse events (AEs), other than laboratory findings. In the N0 subgroup, the rate of discontinuation due to all grade AEs was 24% vs 8% with Kisqali plus ET vs ET alone1,2. No new safety signals were identified1,2.

“Currently available targeted therapies are approved only for a small proportion of patients, leaving a large number of people diagnosed with HR+/HER2- early breast cancer at risk of cancer returning, particularly those with high-risk N0 tumors,” said Jeff Legos, Executive Vice President, Global Head of Oncology Development, Novartis. “Our robust body of data continues to support the potential for Kisqali to benefit many more patients as they seek to reduce the likelihood of their cancer coming back with the addition of a CDK4/6 inhibitor to their endocrine treatment.”

Novartis submitted NATALEE data to the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) in 2023, and further submissions to global authorities are ongoing.

About NATALEE
NATALEE is a global Phase III multi-center, randomized, open-label trial to evaluate the efficacy and safety of Kisqali® (ribociclib) with ET as an investigational adjuvant treatment versus ET alone in patients with stage II and III HR+/HER2- EBC, being conducted in collaboration with TRIO5. The adjuvant ET in both treatment arms was a non-steroidal aromatase inhibitor (NSAI; anastrozole or letrozole) and goserelin if applicable5. The primary endpoint of NATALEE is iDFS as defined by the Standardized Definitions for Efficacy End Points (STEEP) criteria5. A total of 5,101 adult patients with HR+/HER2- EBC across 20 countries were randomized in the trial5.

Results previously announced at the San Antonio Breast Cancer Symposium (SABCS) in December 2023 showed Kisqali plus ET, compared to ET alone, lowered the risk of cancer recurrence by 25.1% (HR=0.749; 95% CI: 0.628, 0.892; p=0.0006), along with consistent clinically meaningful iDFS benefit across key pre-specified subgroups5.

NATALEE explored a lower starting dose (400 mg) of Kisqali than the dose approved for treatment in metastatic breast cancer (MBC) (600 mg) with the goal to minimize disruptions to patient quality of life without compromising efficacy. Compared to the 600 mg dose, the safety profile of Kisqali at 400 mg was observed to have lower rates of symptomatic AEs and less need for dose modifications when administered up to three years5. AEs of special interest (grade 3 or higher) are neutropenia (44.3%), liver-related AEs (e.g., elevated transaminases) (8.6%), and QT interval prolongation (1.0%)1,5.

About Early Breast Cancer
More than 90% of patients diagnosed with breast cancer have EBC7. Despite adjuvant ET or being declared on remission, patients with EBC remain at risk for cancer recurrence, peaking within the first three years after initial diagnosis2. Patients with negative-node disease face a risk of recurrence up to 11% within the first three years after diagnosis, and 29% expect to recur within 20 years2.

About Kisqali® (ribociclib)
Kisqali® (ribociclib) is a selective cyclin-dependent kinase inhibitor, a class of drugs that help slow the progression of cancer by inhibiting two proteins called cyclin-dependent kinase 4 and 6 (CDK4/6). These proteins, when over-activated, can enable cancer cells to grow and divide too quickly. Targeting CDK4/6 with enhanced precision may play a role in ensuring that cancer cells do not continue to replicate uncontrollably.

In MBC, Kisqali has consistently demonstrated statistically significant OS benefit across three Phase III trials8-19. Updates to the NCCN Guidelines® for breast cancer, released in January 2023, recommend ribociclib (Kisqali) as the only Category 1 preferred CDK4/6 inhibitor for first-line treatment of patients with HR+/HER2- when combined with an aromatase inhibitor (AI), making Kisqali the preferred first-line treatment of choice for US prescribers in HR+/HER2- in MBC20. Additionally, Kisqali has the highest rating of any CDK4/6 inhibitor on the ESMO Magnitude of Clinical Benefit Scale, achieving a score of five out of five for first-line pre-menopausal patients with HR+/HER2- advanced breast cancer21. Further, Kisqali in combination with either letrozole or fulvestrant has uniquely, among other CDK4/6 inhibitors, received a score of four out of five for post-menopausal patients with HR+/HER2- advanced breast cancer treated in the first line22.

Kisqali has been approved in 99 countries worldwide, including by the United States Food and Drug Administration (FDA) and the European Commission. In the U.S., Kisqali is approved for the treatment of adult patients with HR+/HER2- advanced or MBC in combination with an AI as initial ET or fulvestrant as initial ET or following disease progression on ET in post-menopausal women or in men. In the EU, Kisqali is approved for the treatment of women with HR+/HER2- advanced or MBC in combination with either an AI or fulvestrant as initial ET or following disease progression. In pre- or peri-menopausal women, the ET should be combined with a luteinizing hormone-releasing hormone agonist23.

Kisqali was developed by the Novartis Institutes for BioMedical Research (NIBR) under a research collaboration with Astex Pharmaceuticals.

Please see full Prescribing Information for Kisqali, available at www.Kisqali.com

About Novartis
Novartis is an innovative medicines company. Every day, we work to reimagine medicine to improve and extend people’s lives so that patients, healthcare professionals and societies are empowered in the face of serious disease. Our medicines reach more than 250 million people worldwide.

Reimagine medicine with us: Visit us at https://www.novartis.com and connect with us on LinkedIn, Facebook, X/Twitter and Instagram.

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https://us.kisqali.com/

Indications KISQALI is a prescription medicine used to treat adults with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer that has gotten worse or has spread to other parts of the body (metastatic), in combination with: an aromatase inhibitor as the first endocrine-based therapy; or fulvestrant as the first endocrine-based therapy or following disease progression on endocrine therapy in postmenopausal women or in men. It is not known if KISQALI is safe and effective in children.

KRAZATI ® (adagrasib)

KRAZATI (adagrasib) Demonstrated Statistically Significant Improvement in Progression-Free Survival in Patients with Pretreated Locally Advanced or Metastatic KRASG12C-Mutated Non-Small Cell Lung Cancer

JUN 01, 2024

First presentation of data from Phase 3 KRYSTAL-12 study showed statistically significant and clinically meaningful improvement in progression-free survival with KRAZATI compared to standard of care chemotherapy

Late-breaking data featured in an oral presentation at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting

PRINCETON, N.J.--(BUSINESS WIRE)-- Bristol Myers Squibb (NYSE: BMY) today announced results from the Phase 3 KRYSTAL-12 study evaluating KRAZATI ® (adagrasib) compared to standard of care chemotherapy in patients with locally advanced or metastatic KRASG12C -mutated non-small cell lung cancer (NSCLC) who had previously received platinum-based chemotherapy, concurrently or sequentially with anti-PD-(L)1 therapy. At a median follow-up of 9.4 months, KRAZATI demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS), the study’s primary endpoint, as assessed by Blinded Independent Central Review (BICR) compared to docetaxel (HR: 0.58; [95% CI, 0.45-0.76]; P <0.0001). Median PFS was 5.5 months for KRAZATI compared to 3.8 months for docetaxel. Overall response rate (ORR) as assessed by BICR was also significantly higher with KRAZATI compared to docetaxel (32% vs 9%; odds ratio, 4.68; P < 0.0001). The median duration of response (mDOR) was 8.31 months (95% CI, 6.05–10.35) versus 5.36 months (95% CI, 2.86–8.54), respectively.

KRAZATI demonstrated intracranial response among patients with central nervous system (CNS) metastases at baseline, with a response rate per BICR that was more than double that observed with docetaxel (24% with KRAZATI vs. 11% with docetaxel).

The KRYSTAL-12 study remains ongoing to assess the additional key secondary endpoint of overall survival.

No new safety signals were identified for KRAZATI, and the safety data were consistent with the known safety profile. Treatment-related adverse events (TRAEs) of any grade were reported in 94% of patients treated with KRAZATI and 86.4% with docetaxel. Grade ≥3 TRAEs occurred in 47% and 46% of patients, respectively.

These data will be presented in a late-breaking oral presentation during the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting on June 1 at 1:27 p.m. CDT (Abstract LBA8509).

“Approximately 14% of all patients with advanced non-small cell lung cancer carry the KRASG12C mutation, impacting thousands of people worldwide,” said Tony Mok, M.D., Chairman of the Department of Clinical Oncology and Li Shu Fan Medical Foundation Professor of Clinical Oncology of the Faculty of Medicine at The Chinese University of Hong Kong (CU Medicine). “These results from the Phase 3 KRYSTAL-12 study reinforce adagrasib as a targeted option for patients with KRASG12C -positive lung cancer after failing standard first-line treatment.”

“The accelerated approval of KRAZATI from the FDA in 2022 was welcome news for patients with KRASG12C -mutated locally advanced or metastatic NSCLC. These confirmatory results further support KRAZATI as an efficacious, targeted treatment option for these patients,” said Abderrahim Oukessou, M.D., vice president, global program lead, KRAZATI, Bristol Myers Squibb. “We look forward to further sharing these results, while also continuing to evaluate KRAZATI in other advanced KRASG12C -mutated solid tumors.”

In addition to KRASG12C -mutated NSCLC, KRAZATI and KRAZATI-based combinations have shown encouraging, meaningful benefit in Phase 2 clinical trials across several tumors, including advanced colorectal cancer, pancreatic cancer, and other solid tumors.

Bristol Myers Squibb thanks the patients and investigators involved in the KRYSTAL-12 clinical trial.

This study was funded by Mirati Therapeutics, Inc., a Bristol Myers Squibb company. KRAZATI is a registered trademark of Mirati Therapeutics, Inc., a Bristol Myers Squibb company.

About KRYSTAL-12

KRYSTAL-12 is an open-label, multicenter, randomized Phase 3 study evaluating KRAZATI compared to standard-of-care chemotherapy alone, in patients with KRASG12C -mutated non-small cell lung cancer. The primary endpoint of the study is progression-free survival (PFS) as assessed by Blinded Independent Central Review (BICR). Secondary endpoints included overall survival (OS), overall response rate (ORR), duration of response (DOR), and safety.

About KRAS G12C - Mutated Non-Small Cell Lung Cancer

Lung cancer is the leading cause of cancer deaths globally. The two main types of lung cancer are non-small cell and small cell. Non-small cell lung cancer (NSCLC) is one of the most common types of lung cancer, representing up to 84% of diagnoses. KRASG12C is the most common KRAS mutation in NSCLC, present in approximately 14% of patients with lung adenocarcinoma, and is a biomarker of poor prognosis.

About KRAZATI ® (adagrasib)

KRAZATI (adagrasib) is a highly selective and potent oral small-molecule inhibitor of KRASG12C that is optimized to sustain target inhibition, an attribute that could be important to treat KRASG12C -mutated cancers, as the KRASG12C protein regenerates every 24-48 hours. KRASG12C mutations act as oncogenic drivers and occur in approximately 14% of non-small cell lung cancer, 3-4% of colorectal cancer, and 1-2% of several other cancers.

In 2022, the U.S. Food and Drug Administration (FDA) granted KRAZATI accelerated approval for treatment of adult patients with KRASG12C -mutated locally advanced or metastatic NSCLC, as determined by an FDA-approved test, who have received at least one prior systemic therapy. This indication is approved under accelerated approval based on objective response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of a clinical benefit in a confirmatory trial(s).

KRAZATI continues to be evaluated as a monotherapy and in combination with other anti-cancer therapies in patients with advanced KRASG12C -mutated solid tumors, including NSCLC and colorectal cancer (CRC).

Please see U.S. Full Prescribing Information for KRAZATI .

INDICATION

KRAZATI is indicated for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer, as determined by an FDA-approved test, who have received at least one prior systemic therapy.

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

https://www.krazati.com/

Please see U.S. Full Prescribing Information for KRAZATI .

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

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. As a leader in cancer care, Bristol Myers Squibb is working to empower all people with cancer to have a better future.

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

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Bristol Myers lung cancer drug Krazati succeeds in late-stage trial

Jun. 01, 2024 8:53 AM ET

Bristol-Myers Squibb Company (BMY) Stock

By: Dulan Lokuwithana, SA News Editor25 Comments

Bristol Myers Squibb (NYSE:BMY) announced Saturday that its FDA-authorized cancer therapy Krazati (adagrasib), acquired with its $4.8B Mirati (MRTX) buyout this year, reached its main goal in a late-stage trial for lung cancer.

https://seekingalpha.com/news/4112126-bristol-myers-wins-late-stage-trial-krazati

Bristol-Myers Squibb Company (BMY) Stock

https://www.krazati.com/

https://www.bms.com/

What is KRAZATI? KRAZATI is a prescription medicine used to treat adults with non-small cell lung cancer (NSCLC): that has spread to other parts of the body or cannot be removed by surgery, and whose tumor has an abnormal KRAS G12C gene, and who have received at least one prior treatment for their cancer Your healthcare provider will perform a test to make sure that KRAZATI is right for you. It is not known if KRAZATI is safe and effective in children.

Risankizumab (SKYRIZI®)

May 31, 2024

AbbVie Receives Positive CHMP Opinion for Risankizumab (SKYRIZI®) for the Treatment of Adults with Moderately to Severely Active Ulcerative Colitis

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The positive opinion is based on results from two pivotal Phase 3 trials, INSPIRE and COMMAND, that evaluated the efficacy and safety of risankizumab in adults with moderately to severely active ulcerative colitis (UC)1,2
In both trials, the primary endpoint of clinical remission (per Adapted Mayo Score*) and key secondary endpoints, including endoscopic improvement** and histologic-endoscopic mucosal improvement,† were met1,2
UC is a chronic, idiopathic, immune-mediated inflammatory bowel disease (IBD) affecting the large intestine. It can lead to a substantial burden and often results in disability3-6

NORTH CHICAGO, Ill., May 31, 2024 /PRNewswire/ -- AbbVie (NYSE: ABBV) today announced that the European Medicines Agency's (EMA's) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending the approval of risankizumab (SKYRIZI®) for the treatment of adults with moderately to severely active UC who have had an inadequate response, lost response, or were intolerant to either conventional or biologic therapy. The recommended induction dose is 1200 mg intravenous (IV), followed by a maintenance dose of 180 mg or 360 mg subcutaneous (SC), based on individual patient presentation. The final European Commission decision is expected in the third quarter of 2024.

"Results from the INSPIRE and COMMAND Phase 3 trials show that patients with moderately to severely active UC can strive for long-term management goals that go beyond symptom control, including histologic-endoscopic mucosal healing," said Edouard Louis, M.D., Ph.D., professor and head of gastroenterology, Liège University Hospital; dean of faculty, Liège University; and INSPIRE trial investigator. "This finding is significant since treatment goals for patients are evolving beyond symptom management to include endoscopic remission.7-9 Studies have shown that endoscopic improvement may be associated with favorable longer-term outcomes, including lower risk of hospitalizations and improved quality of life."10-12

The CHMP positive opinion is supported by data from two Phase 3 clinical trials: the INSPIRE induction trial1 and the COMMAND maintenance trial.2 The INSPIRE trial evaluated 1200 mg of IV risankizumab administered as an induction dose at 0, 4 and 8 weeks in patients with moderately to severely active UC. In the COMMAND trial, patients who responded to induction treatment in INSPIRE were rerandomized to receive 180 mg or 360 mg of SC risankizumab as maintenance doses for an additional 52 weeks. The safety profile of risankizumab in both trials was consistent with the safety profile observed in previous trials across other indications, with no new safety risks observed.1,2

"At AbbVie, patients are at the heart of everything we do," said Kori Wallace, M.D., Ph.D., vice president, immunology clinical development, AbbVie. "We are motivated to bring new treatment options to patients in need through our commitment to ongoing research and development in gastroenterology. We eagerly await the EMA's final decision for risankizumab on its use in UC which has the potential to help patients meet their long-term treatment goals."

Use of risankizumab in UC is not approved in the European Union, and its safety and efficacy remain under evaluation.

Risankizumab (SKYRIZI) is part of a collaboration between Boehringer Ingelheim and AbbVie, with AbbVie leading development and commercialization globally.

*Adapted Mayo Score is based on stool frequency subscore (SFS), rectal bleeding subscore (RBS) and endoscopic subscore (ES).
**Endoscopic improvement is defined as ES ≤1 without evidence of friability.
†Histologic-endoscopic mucosal improvement (HEMI) is defined as an ES of ≤1 without evidence of friability and Geboes score ≤3.1.

About Ulcerative Colitis (UC)
UC is a chronic, idiopathic, immune-mediated IBD of the large intestine that causes continuous mucosal inflammation extending, to a variable extent, from the rectum to the more proximal colon.3,4 The hallmark signs and symptoms of UC include rectal bleeding, abdominal pain, bloody diarrhea, tenesmus (a sense of pressure), urgency and fecal incontinence.4,5 The disease course of UC varies between patients and can range from quiescent disease to chronic refractory disease, which in some cases can lead to surgery or life-threatening complications.4,5 The severity of symptoms and unpredictability of disease course can lead to substantial burden and often disability among those living with the disease.6

About the INSPIRE Induction Trial1
INSPIRE is a Phase 3, multicenter, randomized, double-blind, placebo-controlled trial evaluating the efficacy and safety of IV risankizumab 1200 mg administered at 0, 4 and 8 weeks as induction therapy in patients with moderately to severely active UC. The primary endpoint of the trial is clinical remission (per Adapted Mayo Score, defined as SFS ≤1 and not greater than baseline, RBS of 0 and ES ≤1 without friability) at week 12. Key secondary endpoints include clinical response (decrease from baseline in the Adapted Mayo Score ≥2 points and ≥30% from baseline, plus a decrease in RBS ≥1 or an absolute RBS ≤1), endoscopic improvement (ES ≤1 without friability) and HEMI (ES of 0 or 1 without friability and Geboes score ≤3.1) at week 12.

Top-line results of the study were shared in March 2023. More information can be found on www.clinicaltrials.gov (NCT03398148).

About the COMMAND Maintenance Trial2
COMMAND is a Phase 3, multicenter, randomized, double-blind, controlled, 52-week maintenance trial designed to evaluate the efficacy and safety of SC risankizumab 180 mg or 360 mg in adults with moderately to severely active UC. This study had a rerandomized withdrawal design in which all patients received risankizumab IV induction, and those who responded to risankizumab IV were rerandomized to receive SC risankizumab 180 mg or 360 mg or withdrawal from risankizumab treatment (induction-only control group). For those patients randomized to withdraw from risankizumab treatment (induction-only control group), the rest of the study duration was a risankizumab washout. The objective of the Phase 3 trial is to evaluate the efficacy and safety of risankizumab 180 mg or 360 mg as maintenance therapy versus withdrawal from risankizumab treatment (control) in patients with moderately to severely active UC who responded to risankizumab IV induction in the INSPIRE trial.

The primary endpoint of the trial is clinical remission (per Adapted Mayo Score, defined as SFS ≤1 and not greater than baseline, RBS of 0 and ES ≤1 without evidence of friability) at week 52. Key secondary endpoints include endoscopic improvement (ES ≤1 without evidence of friability), HEMI (ES of ≤1 without evidence of friability and Geboes score ≤3.1), and steroid-free clinical remission at week 52 (defined as clinical remission per Adapted Mayo Score at week 52 and corticosteroid free for ≥90 days prior to week 52).

Top-line results from this study were shared in June 2023. More information can be found on www.clinicaltrials.gov (NCT03398135).

About Risankizumab (SKYRIZI)
SKYRIZI is an interleukin (IL)-23 inhibitor that selectively blocks IL-23 by binding to its p19 subunit.13 IL-23, a cytokine involved in inflammatory processes, is thought to be linked to a number of chronic immune-mediated diseases.14,15 SKYRIZI is approved by the U.S. Food and Drug Administration and the EMA for the treatment of plaque psoriasis, psoriatic arthritis, and Crohn's disease.13,16

https://www.skyrizi.com/

EU Indications and Important Safety Information About Risankizumab (SKYRIZI)13
SKYRIZI is indicated for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy. SKYRIZI, alone or in combination with methotrexate, is indicated for the treatment of active psoriatic arthritis in adults who have had an inadequate response or who have been intolerant to one or more disease-modifying antirheumatic drugs. SKYRIZI is indicated for the treatment of adult patients with moderately to severely active Crohn's disease who have had an inadequate response to, lost response to, or were intolerant to conventional or biologic therapy.

SKYRIZI is contraindicated in patients hypersensitive to the active substance or to any of its excipients and in patients with clinically important active infections (e.g., active tuberculosis [TB]). SKYRIZI may increase the risk of infection. In patients with a chronic infection, a history of recurrent infection, or known risk factors for infection, SKYRIZI should be used with caution. Treatment with SKYRIZI should not be initiated in patients with any clinically important active infection until the infection resolves or is adequately treated.

Patients treated with SKYRIZI should be instructed to seek medical advice if signs or symptoms of clinically important chronic or acute infection occur. If a patient develops such an infection or is not responding to standard therapy for the infection, the patient should be closely monitored, and SKYRIZI should not be administered until the infection resolves.

Prior to initiating treatment with SKYRIZI, patients should be evaluated for TB infection. Patients receiving SKYRIZI should be monitored for signs and symptoms of active TB. Anti-TB therapy should be considered prior to initiating SKYRIZI in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed.

Prior to initiating therapy with SKYRIZI, completion of all appropriate immunizations should be considered according to current immunization guidelines. If a patient has received live vaccination (viral or bacterial), it is recommended to wait at least 4 weeks prior to starting treatment with SKYRIZI. Patients treated with SKYRIZI should not receive live vaccines during treatment and for at least 21 weeks after treatment.

If a serious hypersensitivity reaction occurs, administration of SKYRIZI should be discontinued immediately, and appropriate therapy initiated.

The most frequently reported adverse reactions were upper respiratory infections (from 13% in psoriasis to 15.6% in Crohn's disease). Commonly (≥1/100 to <1/10) reported adverse reactions included tinea infections, headache, pruritus, fatigue, and injection site reactions.

This is not a complete summary of all safety information.

See the full Summary of Product Characteristics (SmPC) for SKYRIZI at www.ema.europa.eu.

Globally, prescribing information varies; refer to the individual country product label for complete information.

About AbbVie in Gastroenterology
With a robust clinical trial program, AbbVie is committed to cutting-edge research to drive exciting developments in IBD, like ulcerative colitis and Crohn's disease. By innovating, learning, and adapting, AbbVie aspires to eliminate the burden of IBD and make a positive long-term impact on the lives of people with IBD. For more information on AbbVie in gastroenterology, visit https://www.abbvie.com/our-science/therapeutic-focus-areas/immunology/immunology-focus-areas/gastroenterology.html.

About AbbVie
AbbVie's mission is to discover and deliver innovative medicines and solutions that solve serious health issues today and address the medical challenges of tomorrow. We strive to have a remarkable impact on people's lives across several key therapeutic areas — immunology, oncology, neuroscience, and eye care — and products and services in our Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on LinkedIn, Facebook, Instagram, X (formerly Twitter), and YouTube.

SOURCE AbbVie

AbbVie wins EU backing for Skyrizi in bowel disorder

May 31, 2024 7:10 AM ET

AbbVie Inc. (ABBV) Stock

By: Dulan Lokuwithana, SA News Editor8 Comments

AbbVie (NYSE:ABBV) announced Friday that an expert panel of the EU drug regulator endorsed its arthritis therapy risankizumab (Skyrizi) as a late-line therapy for adults with ulcerative colitis, an inflammatory bowel disorder.
https://seekingalpha.com/news/4111879-abbvie-skyrizi-endorsed-eu-bowel-disorder
AbbVie Inc. (ABBV) Stock
https://www.abbvie.com/
https://www.skyrizi.com/

USES SKYRIZI is a prescription medicine used to treat adults with: moderate to severe plaque psoriasis who may benefit from taking injections or pills (systemic therapy) or treatment using ultraviolet or UV light (phototherapy). active psoriatic arthritis (PsA). moderate to severe Crohn's disease.

KEYTRUDA® (pembrolizumab) Plus Chemotherapy

FDA Grants Priority Review to Merck’s Application for KEYTRUDA® (pembrolizumab) Plus Chemotherapy as First-Line Treatment of Patients With Unresectable Advanced or Metastatic Malignant Pleural Mesothelioma

May 29, 2024 7:15 am ET

Acceptance based on results from the pivotal Phase 3 CCTG IND.227/KEYNOTE-483 trial, which demonstrated a statistically significant improvement in overall survival versus chemotherapy alone in these patients

The sBLA is based on data from the pivotal Phase 2/3 IND.227/KEYNOTE-483 trial. Results from the final analysis of the study, presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, showed KEYTRUDA in combination with chemotherapy demonstrated a statistically significant improvement in overall survival (OS), reducing the risk of death by 21% (HR=0.79 [95% CI, 0.64-0.98]; two-sided p value=0.0324), with a median OS of 17.3 months (95% CI, 14.4-21.3) versus 16.1 months (95% CI, 13.1-18.2) for chemotherapy alone. KEYTRUDA plus chemotherapy also demonstrated a significant improvement in progression-free survival (PFS) (HR=0.80 [95%CI, 0.65-0.99], two-sided p value = 0.0372; median PFS 7.13 months versus 7.16 months respectively) and objective response rate (ORR) compared to chemotherapy alone. At 12 months, the estimated PFS rate was 26% for KEYTRUDA plus chemotherapy versus 17% for chemotherapy alone. The ORR was significantly higher for KEYTRUDA plus chemotherapy versus chemotherapy alone (62% versus 38%, p<0.0001). The safety profile of KEYTRUDA plus chemotherapy in this study was consistent with previously reported studies.

“Malignant pleural mesothelioma is typically diagnosed in advanced stages when curative surgery is not an option, and progresses quickly,” said Dr. Gregory Lubiniecki, vice president, oncology clinical research, Merck Research Laboratories. “We continue to evaluate KEYTRUDA in new and difficult-to-treat tumors and look forward to working with the FDA to help bring KEYTRUDA as a potential treatment option to certain patients with advanced malignant pleural mesothelioma.”

About IND.227/KEYNOTE-483

IND.227/KEYNOTE-483 is a randomized, open-label Phase 2/3 trial (ClinicalTrials.gov, NCT02784171) sponsored and conducted by Canadian Cancer Trials Group (CCTG) in collaboration with National Cancer Institute of Naples (NCIN) and Intergroupe Francophone de Cancérologie Thoracique (IFCT). Merck provided KEYTRUDA and support for the trial. The trial evaluated KEYTRUDA plus chemotherapy versus chemotherapy alone for the treatment of patients with unresected advanced pleural mesothelioma. The study’s primary endpoint is OS and secondary endpoints include PFS and ORR as assessed by blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) modified for mesothelioma, safety and quality of life. The Phase 3 part of the trial enrolled 440 patients who were randomized to receive:

KEYTRUDA (200 mg intravenously [IV] every three weeks [Q3W] for up to 35 cycles) plus pemetrexed (500 mg/m2 Q3W for six cycles) and cisplatin (75 mg/m2 Q3W for six cycles; carboplatin substitution [AUC 5-6 Q3W for six cycles] was permitted), or
Pemetrexed and cisplatin (carboplatin substitution was permitted) alone.

About malignant mesothelioma

Malignant mesothelioma is a type of cancer that starts in the linings of certain parts of the body, including the chest, abdomen, heart and testicles. Worldwide, it is estimated there were more than 30,000 new cases of mesothelioma diagnosed and more than 25,000 deaths from the disease in 2022. Although the incidence of malignant mesothelioma has gradually declined in the U.S., continued use of and exposure to asbestos around the world has resulted in increasing global rates of this aggressive disease. Pleural mesothelioma, which develops in the lining of the lungs, is the most common form of malignant mesothelioma, accounting for about 75% of all cases. Malignant pleural mesothelioma often progresses rapidly, and the five-year survival rate is only 12%.

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.

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.

KEYTRUDA is indicated for the treatment of patients with resectable (tumors ≥4 cm or node positive) NSCLC in combination with platinum-containing chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.

KEYTRUDA, as a single agent, is indicated as adjuvant treatment following resection and platinum-based chemotherapy for adult patients with stage IB (T2a ≥4 cm), II, or IIIA NSCLC.

https://www.keytruda.com/

Additional Selected KEYTRUDA 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.

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 Cancer

KEYTRUDA, in combination with enfortumab vedotin, is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma:

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.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) 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 adults with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.

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

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

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 chemoradiotherapy (CRT), is indicated for the treatment of patients with FIGO 2014 Stage III-IVA 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) secondary to hepatitis B who have received prior systemic therapy other than a PD-1/PD-L1–containing regimen.

Biliary Tract Cancer

KEYTRUDA, in combination with gemcitabine and cisplatin, is indicated for the treatment of patients with locally advanced unresectable or metastatic biliary tract cancer (BTC).

Merkel Cell Carcinoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC).

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 (mut/Mb)] 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.

Merck’s focus on cancer

Every day, we follow the science as we work to discover innovations that can help patients, no matter what stage of cancer they have. As a leading oncology company, we are pursuing research where scientific opportunity and medical need converge, underpinned by our diverse pipeline of more than 25 novel mechanisms. With one of the largest clinical development programs across more than 30 tumor types, we strive to advance breakthrough science that will shape the future of oncology. By addressing barriers to clinical trial participation, screening and treatment, we work with urgency to reduce disparities and help ensure patients have access to high-quality cancer care. Our unwavering commitment is what will bring us closer to our goal of bringing life to more patients with cancer. For more information, visit https://www.merck.com/research/oncology/.

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 X (formerly 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 https://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_mg.pdf .

Source: Merck & Co., Inc.

https://seekingalpha.com/symbol/MRK

https://www.merck.com/

https://www.nasdaq.com/market-activity/stocks/mrk/dividend-history

https://www.keytruda.com/

LORBRENA® (lorlatinib)

Pfizer’s LORBRENA® CROWN Study Shows Majority of Patients with ALK-Positive Advanced Lung Cancer Living Beyond Five Years Without Disease Progression

Friday, May 31, 2024 - 08:00am View pdf

An unprecedented 60% of patients remain alive without disease progression after five years
Updated results show continued 81% reduction in risk of progression or death and 94% reduction in progression of brain metastases compared to XALKORI®

NEW YORK--(BUSINESS WIRE)-- Pfizer Inc. (NYSE: PFE) today announced longer-term follow-up results from the Phase 3 CROWN trial evaluating LORBRENA® (lorlatinib, a third-generation ALK inhibitor, available in Europe under the brand name LORVIQUA®) versus XALKORI® (crizotinib) in people with previously untreated, anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC). After five years of median follow-up, median progression-free survival (PFS) based on investigator assessment was not reached with LORBRENA, with an observed Hazard Ratio (HR) of 0.19 (95% Confidence Interval [CI], 0.13-0.27), representing an 81% reduction in the rate of disease progression or death compared to XALKORI. Further, 60% of patients treated with LORBRENA (95% CI, 51-68) were alive without disease progression after five years compared to 8% (3-14) on the XALKORI treatment arm. These data will be presented today in an oral presentation at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract LBA8503) and have been simultaneously published in the Journal of Clinical Oncology.

“These results from the CROWN trial are unprecedented, as the majority of patients on LORBRENA are living beyond five years without disease progression,” said Roger Dansey, M.D., Chief Development Officer, Oncology, Pfizer. “These results are an excellent example of Pfizer’s long-standing commitment to discovering and developing scientific breakthroughs for patients, and support LORBRENA as a standard of care for the first-line treatment of people with ALK-positive advanced NSCLC.”

Lung cancer is the number one cause of cancer-related death around the world,i and an estimated 234,580 new cases of lung cancer are expected to be diagnosed in the U.S. in 2024.ii NSCLC accounts for approximately 80-85% of lung cancers,iii with ALK-positive tumors occurring in about 3-5% of NSCLC cases.iv Approximately 25-40% of people with ALK-positive advanced NSCLC may develop brain metastases within two years from initial diagnosis.v LORBRENA was specifically designed and developed by Pfizer to inhibit tumor mutations that drive resistance to other ALK inhibitors and to penetrate the blood-brain barrier.

“ALK-positive advanced NSCLC is typically aggressive and often impacts younger people in the prime of their lives,” said Benjamin Solomon, MBBS, Ph.D., Department of Medical Oncology, Peter MacCallum Cancer Centre, and Principal Investigator of the CROWN trial. “This updated analysis shows that LORBRENA helped patients live longer without disease progression, with the majority of patients experiencing sustained benefit for over five years, including nearly all patients having protection from progression of disease in the brain. These improvements in outcomes for patients with ALK-positive NSCLC represent a remarkable advancement in lung cancer.”

In this updated analysis, LORBRENA showed a 94% reduction in the risk of developing intracranial (IC) progression (HR, 0.06; 95% CI, 0.03-0.12). The median time to IC progression was not reached (95% CI, NR-NR) with LORBRENA and was 16.4 months (12.7-21.9) with XALKORI. In people without brain metastases at baseline receiving LORBRENA, only 4 of 114 developed brain metastases within the first 16 months of treatment, compared to 39 of 109 patients who received XALKORI. At the time of analysis, 50% of patients in the CROWN trial were still receiving LORBRENA compared to 5% of patients receiving XALKORI.

“Although ALK-positive advanced NSCLC accounts for only approximately five percent of all NSCLC cases, this translates to 72,000 people who are diagnosed worldwide each year,” said Kenneth Culver, M.D., Director of Research and Clinical Affairs at the non-profit organization ALK Positive. “These new results of the CROWN trial symbolize significant progress in the first-line setting for the targeted treatment of ALK-positive lung cancer, which has led to notable improvements for the patient community.”

The safety profiles of LORBRENA and XALKORI in the five-year follow-up were consistent with previous findings, with no new safety signals reported for LORBRENA. In this analysis, the most frequent (≥20%) adverse events (AEs) reported in patients treated with LORBRENA were consistent with the 2020 analysis of the CROWN trial, which included edema, weight gain, peripheral neuropathy, cognitive effects, mood effects, diarrhea, dyspnea, arthralgia, hypertension, headache, cough, pyrexia, hypercholesterolemia, and hypertriglyceridemia. Grade 3/4 AEs occurred in 77% of patients with LORBRENA and in 57% of patients with XALKORI. Treatment-related AEs led to permanent treatment discontinuation in 5% and 6% of patients in the LORBRENA and XALKORI arms, respectively.

Pfizer is continuing its commitment to help non-scientists understand the latest findings with the development of abstract plain language summaries (APLS) for company-sponsored research being presented at ASCO, which are written in non-technical language. Those interested in learning more can visit www.Pfizer.com/apls to access the summaries.

About the CROWN Trial

CROWN is a Phase 3, randomized, open-label, parallel 2-arm trial in which 296 people with previously untreated ALK-positive advanced NSCLC were randomized 1:1 to receive LORBRENA monotherapy (n=149) or XALKORI monotherapy (n=147). The primary endpoint of the CROWN trial is PFS based on Blinded Independent Central Review (BICR). Secondary endpoints include PFS based on investigator’s assessment, overall survival (OS), objective response rate (ORR), intracranial objective response (IOR), and safety. Given that median PFS was not reached after three years of follow-up, an unplanned post hoc analysis was executed with the intent to further quantify long-term outcomes based on investigator tumor assessment from this study at a clinically meaningful landmark follow-up of five years.

About LORBRENA® (lorlatinib)

LORBRENA is approved in the U.S. for the treatment of adults with metastatic NSCLC whose tumors are ALK-positive as detected by an FDA-approved test.

Please see Full Prescribing Information for LORBRENA® (lorlatinib) or visit https://www.lorbrena.com.

https://www.lorbrena.com/

About Pfizer Oncology

About Pfizer: Breakthroughs That Change Patients’ Lives

At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development, and manufacture of health care products, including innovative medicines and vaccines. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments, and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world’s premier innovative biopharmaceutical companies, we collaborate with health care providers, governments, and local communities to support and expand access to reliable, affordable health care around the world. For more than 175 years, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on our website at www.Pfizer.com. In addition, to learn more, please visit us on www.Pfizer.com and follow us on X at @Pfizer and @Pfizer News, LinkedIn, YouTube and like us on Facebook at Facebook.com/Pfizer.

Source: Pfizer Inc.

Pfizer posts long-term data to support lung cancer therapy Lorbrena

May 31, 2024 9:48 AM ET

Pfizer Inc. (PFE) Stock

By: Dulan Lokuwithana, SA News Editor7 Comments

Pfizer (NYSE:PFE) announced new long-term data to support its lung cancer therapy Lorbrena (lorlatinib) on Friday. The company noted that the FDA-approved oral treatment cut the risk of disease progression or death by 81% in a late-stage trial for advanced non-small cell lung cancer (NSCLC).

The readout was based on its Phase 3 CROWN trial, which enrolled previously untreated NSCLC patients whose cancers were positive for the anaplastic lymphoma kinase (ALK) receptor. They were randomized to receive Lorbrena or Pfizer’s (PFE) lung cancer therapy, Xalkori.

https://seekingalpha.com/news/4111942-pfizer-data-supports-lung-cancer-drug-lorbrena?mailingid=35559545&messageid=2900&serial=35559545.10523&utm_campaign=rta-stock-news&utm_content=link-1&utm_medium=email&utm_source=seeking_alpha&utm_term=35559545.10523

Pfizer Inc. (PFE) Stock

https://www.pfizer.com/

https://www.lorbrena.com/

Indication LORBRENA is a prescription medicine that is used to treat adults with non-small cell lung cancer (NSCLC) that is caused by an abnormal anaplastic lymphoma kinase (ALK) gene and that has spread to other parts of your body. Your healthcare provider will perform a test to make sure that LORBRENA is right for you. It is not known if LORBRENA is safe and effective in children.

Breyanzi ® (lisocabtagene maraleucel; liso-cel)

U.S. Food and Drug Administration Approves Bristol Myers Squibb’s Breyanzi as a New CAR T Cell Therapy for Relapsed or Refractory Mantle Cell Lymphoma

05/30/2024 CATEGORY: Corporate/Financial News

UNDERSTANDING THE CAR T CELL THERAPY TREATMENT EXPERIENCE MCL INFOGRAPHIC

In the MCL cohort of TRANSCEND NHL 001, Breyanzi delivered responses in 85.3% of patients with a one-time infusion while demonstrating a consistent safety profile across clinical trials

Breyanzi is the only CAR T cell therapy approved by the FDA for four distinct subtypes of non-Hodgkin lymphoma, bringing this personalized therapy to the broadest array of patients with B-cell malignancies

PRINCETON, N.J.--(BUSINESS WIRE)-- Bristol Myers Squibb (NYSE: BMY) today announced the U.S. Food and Drug Administration (FDA) has granted approval for Breyanzi ® (lisocabtagene maraleucel; liso-cel), a CD19-directed chimeric antigen receptor (CAR) T cell therapy, for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL) who have received at least two prior lines of systemic therapy, including a Bruton tyrosine kinase (BTK) inhibitor. This FDA approval marks the fourth distinct subtype of non-Hodgkin lymphoma for which Breyanzi is approved, making it the CAR T cell therapy available to treat the broadest array of B-cell malignancies. In relapsed or refractory MCL, Breyanzi is delivered as a one-time infusion* with a single dose containing 90 to 110 x 106 CAR-positive viable T cells. Please see the Important Safety Information section below, including Boxed WARNINGS for Breyanzi regarding Cytokine Release Syndrome (CRS), Neurologic Toxicities, and Secondary Hematological Malignancies.

Product image for download (Photo: Bristol Myers Squibb)

“With Breyanzi, we are delivering on the promise of cell therapy by offering a definitive treatment option for some of the most difficult-to-treat lymphomas,” said Bryan Campbell, senior vice president, Head of Commercial, Cell Therapy, Bristol Myers Squibb. “We are proud of the advances we are making to bring our differentiated CAR T cell therapy to the most patients across indications and lines of therapy to ensure treatment options that provide improved outcomes are available when most needed.”

MCL is a rare but aggressive form of non-Hodgkin lymphoma, and many patients relapse or become resistant to frontline therapies. Currently, MCL is considered an incurable disease, and response rates and duration of response tend to decrease with each additional relapse.

“There have been few advances in the treatment of relapsed or refractory MCL, and prognosis worsens for patients after each subsequent relapse, often leaving them with high disease burden and difficulty achieving deep and durable responses,” said Michael Wang, M.D., lead investigator and Puddin Clarke Endowed Professor, Department of Lymphoma and Myeloma, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas. “The approval of Breyanzi offers an important new CAR T treatment option with high rates of lasting responses and a consistent safety profile, which is critically important for these patients who currently have limited options to treat this aggressive disease.”

The approval of Breyanzi is based on results from the MCL cohort of TRANSCEND NHL 001, which enrolled adults with relapsed or refractory MCL who had previously received at least two or more prior lines of therapy, including a BTK inhibitor. Based on the U.S. Prescribing Information (USPI), in patients treated with Breyanzi and evaluated for efficacy (n=68), 85.3% (95% CI: 74.6-92.7) responded to treatment, with 67.6% (95% CI: 55.2-78.5) achieving a complete response (CR). Responses were assessed per the 2014 Lugano classification and required bone marrow biopsy to confirm CR. Responses were rapid and durable with a median time to response of one month (range: 0.7-3) and median duration of response of 13.3 months (95% CI: 6.0-23.3) with a median follow-up of 22.2 months (95% CI: 16.7-22.8). More than half (51.4%; 95% CI: 37.5-63.7) of responders remained in response at 12 months, and 38.8% (95% CI: 25-52.4) of responders remained in response at 18 months. Results from the primary analysis published in the Journal of Clinical Oncology (JCO) (n=83; DL1 + DL2) showed an overall response rate of 83.1% (95% CI: 73.3-90.5) and a CR rate of 72.3% (95% CI: 61.4 to 81.6). Median duration of response was 15.7 months (95% CI: 6.2 to 24.0) and progression-free survival was 15.3 months (95% CI: 6.6 to 24.9).

Breyanzi has exhibited a consistent safety profile across clinical trials (n=702) with any grade cytokine release syndrome (CRS) occurring in 54% of patients, including Grade >3 CRS in 3.2% of patients. The median time to onset was 5 days (range: 1 to 63 days). Any grade neurologic events (NEs) were reported in 31% of patients, including Grade >3 in 10% of patients. The median time to onset of NEs was 8 days (range: 1 to 63 days). NEs resolved in 88% of patients with a median duration of 7 days (range: 1 to 119 days). The safety profile of Breyanzi allows for the option of outpatient treatment and management of patients. Breyanzi was administered in the inpatient and outpatient setting in the MCL cohort of TRANSCEND NHL 001.

“The approval of Breyanzi brings a new CAR T cell therapy option to patients battling relapsed or refractory MCL,” said Meghan Gutierrez, chief executive officer, Lymphoma Research Foundation. “Each advance in treatment represents important progress in improving outcomes for patients, and this news builds upon this progress with a new potentially transformative treatment where there are currently limited options. We are thankful for the families and the researchers involved in making this approval a reality for those living with this disease.”

To support this additional indication for Breyanzi, Bristol Myers Squibb has made continuous investments to increase manufacturing capacity and is prepared to meet demand for Breyanzi.

Breyanzi is broadly covered by commercial and government insurance programs in the U.S. Bristol Myers Squibb offers various programs and resources to address the needs of patients and caregivers, and provides support that allows for access to therapies, including Breyanzi. Bristol Myers Squibb also supports the patient and physician treatment experience by providing Cell Therapy 360, a digital service platform, which optimizes access to relevant information, manufacturing updates, and patient and caregiver support.

*Treatment process includes leukapheresis, manufacturing, administration and adverse event monitoring.

About TRANSCEND NHL 001

TRANSCEND NHL 001 (NCT02631044) is an open-label, multicenter, pivotal, Phase 1, single-arm, seamless-design study to determine the safety, pharmacokinetics and antitumor activity of Breyanzi in patients with relapsed or refractory B-cell non-Hodgkin lymphoma, including diffuse large B-cell lymphoma, high-grade B-cell lymphoma, primary mediastinal B-cell lymphoma, follicular lymphoma Grade 3B and mantle cell lymphoma. The primary outcome measures are treatment-related adverse events, dose-limiting toxicities and overall response rate. Secondary outcome measures include complete response rate, duration of response, and progression-free survival.

About MCL

Mantle cell lymphoma (MCL) is an aggressive, rare form of non-Hodgkin lymphoma (NHL), representing roughly 3% of all NHL cases. MCL originates from cells in the “mantle zone” of the lymph node. MCL occurs more frequently in older adults with an average age at diagnosis in the mid-60s, and it is more often found in males than in females. In MCL, relapse after initial treatment is common, and for most, the disease eventually progresses or returns.

About Breyanzi

Breyanzi is a CD19-directed CAR T cell therapy with a 4-1BB costimulatory domain, which enhances the expansion and persistence of the CAR T cells. Breyanzi is made from a patient’s own T cells, which are collected and genetically reengineered to become CAR T cells that are then delivered via infusion as a one-time treatment.

Breyanzi is approved in the U.S. for the treatment of relapsed or refractory large B-cell lymphoma (LBCL) after at least one prior line of therapy, and has received accelerated approval for the treatment of relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma after at least two prior lines of therapy, and relapsed or refractory follicular lymphoma in the third-line plus setting. Breyanzi is also approved in Japan, the European Union (EU), and Switzerland for the second-line treatment of relapsed or refractory LBCL, and in Japan, the EU, Switzerland, the UK and Canada for relapsed and refractory LBCL after two or more lines of systemic therapy.

Bristol Myers Squibb’s clinical development program for Breyanzi includes clinical studies in other types of lymphoma. For more information, visit clinicaltrials.gov.

Indications

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

adult patients with large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B, who have:
- refractory disease to first-line chemoimmunotherapy or relapse within 12 months of first-line chemoimmunotherapy; or
- refractory disease to first-line chemoimmunotherapy or relapse after first-line chemoimmunotherapy and are not eligible for hematopoietic stem cell transplantation (HSCT) due to comorbidities or age; or
- relapsed or refractory disease after two or more lines of systemic therapy.

Limitations of Use: BREYANZI is not indicated for the treatment of patients with primary central nervous system lymphoma.

adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have received at least 2 prior lines of therapy, including a Bruton tyrosine kinase (BTK) inhibitor and a B-cell lymphoma 2 (BCL-2) inhibitor. This indication is approved under accelerated approval based on response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
adult patients with relapsed or refractory follicular lymphoma (FL) who have received 2 or more prior lines of systemic therapy. This indication is approved under accelerated approval based on response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
adult patients with relapsed or refractory mantle cell lymphoma (MCL) who have received at least 2 prior lines of systemic therapy, including a Bruton tyrosine kinase (BTK) inhibitor.
https://www.breyanzi.com/lbcl

BREYANZI REMS

Because of the risk of CRS and neurologic toxicities, BREYANZI is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the BREYANZI REMS. The required components of the BREYANZI REMS are:

Healthcare facilities that dispense and administer BREYANZI must be enrolled and comply with the REMS requirements.
Certified healthcare facilities must have on-site, immediate access to tocilizumab.
Ensure that a minimum of 2 doses of tocilizumab are available for each patient for infusion within 2 hours after BREYANZI infusion, if needed for treatment of CRS.

Further information is available at www.BreyanziREMS.com, or contact Bristol-Myers Squibb at 1-866-340-7332.

Please see full Prescribing Information , including Boxed WARNINGS and Medication Guide .

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

Learn more about the science behind cell therapy and ongoing research at Bristol Myers Squibb here.

About Bristol Myers Squibb

Source: Bristol Myers Squibb

Bristol Myers' Breyanzi gains additional indication for mantle cell lymphoma

May 30, 2024 12:22 PM ET

Bristol-Myers Squibb Company (BMY) Stock

By: Jonathan Block, SA News Editor

The U.S. FDA has approved Bristol-Myers Squibb's (NYSE:BMY) CAR-T therapy Breyanzi (lisocabtagene maraleucel) as a third-line treatment for mantle cell lymphoma.
In relapsed or refractory MCL, Breyanzi is given as a one-time infusion.
https://seekingalpha.com/news/4111641-bristol-myers-squibb-breyanzi-gains-additional-indication-mantle-cell-lymphoma
Bristol-Myers Squibb Company (BMY) Stock
https://www.bms.com/
https://www.breyanzi.com/lbcl
https://www.breyanzirems.com/

Indication BREYANZI is a prescription medicine used to treat large B cell lymphoma, a type of non-Hodgkin lymphoma, when: your first treatment has not worked or your cancer returned within a year of your first treatment OR your first treatment has not worked or your cancer returned after the first treatment, and you are not eligible for hematopoietic stem cell transplantation because of medical conditions or age OR two or more kinds of treatment have not worked or stopped working. BREYANZI is different than other cancer medicines because it is made from your own white blood cells, which have been genetically modified to recognize and attack your lymphoma cells.

Opdivo® (nivolumab) in Combination with Cisplatin and Gemcitabine

Bristol Myers Squibb Receives European Commission Approval for Opdivo® (nivolumab) in Combination with Cisplatin and Gemcitabine for the First-Line Treatment of Adult Patients with Unresectable or Metastatic Urothelial Carcinoma

05/29/2024CATEGORY:

Corporate/Financial News

Approval based on results from CheckMate -901, the first Phase 3 trial in this patient population with an immunotherapy-chemotherapy combination to demonstrate survival benefit versus standard-of-care chemotherapy alone

First concurrent immunotherapy-chemotherapy combination approved for this patient population in the European Union

PRINCETON, N.J.--(BUSINESS WIRE)-- Bristol Myers Squibb (NYSE: BMY) today announced that the European Commission (EC) has approved Opdivo® (nivolumab) in combination with cisplatin and gemcitabine for the first-line treatment of adult patients with unresectable or metastatic urothelial carcinoma (UC). With this approval, Opdivo in combination with cisplatin and gemcitabine becomes the first concurrent immunotherapy-chemotherapy approved for the treatment of adult patients with unresectable or metastatic UC in the first-line setting in the European Union.

“With today’s approval by the EC, we’re pleased to be able to offer Opdivo concurrently with chemotherapy to eligible patients with unresectable or metastatic UC,” said Dana Walker, M.D., M.S.C.E., vice president and global program lead, gastrointestinal and genitourinary cancers, Bristol Myers Squibb. “This is a major step forward for this patient population and reinforces our goal of advancing and delivering new options to patients with difficult-to-treat cancers. We extend our sincerest gratitude to the patients, their families, investigators and staff who contributed to this important research.”

The EC’s decision is based on results from the CheckMate -901 trial studying Opdivo in combination with cisplatin and gemcitabine, which were presented at the European Society of Medical Oncology (ESMO) Congress 2023. In CheckMate -901, Opdivo in combination with cisplatin and gemcitabine followed by Opdivo monotherapy demonstrated statistically significant and clinically meaningful improvements in the primary efficacy endpoints of overall survival (OS) and progression-free survival (PFS) compared to chemotherapy alone, as assessed by Blinded Independent Central Review (BICR). The safety profile was consistent with the known safety profiles of the individual components of the regimen. No new safety concerns were identified.

“In the CheckMate -901 trial, the combination of Opdivo with cisplatin and gemcitabine improved overall survival, reduced the risk of disease progression or death by 28% versus chemo alone, and demonstrated deep and durable responses versus chemo alone,” said Michiel Van der Heijden, M.D, Ph.D., medical oncologist and research group leader, Netherlands Cancer Institute. “These findings are significant and reinforce that concurrent Opdivo and chemotherapy should be considered as a new standard of care for the first line treatment of eligible patients with this difficult-to-treat cancer.”

This approval by the EC for Opdivo in combination with cisplatin and gemcitabine for the first-line treatment of adult patients with unresectable or metastatic UC is valid in all 27 member states of the EU, as well as Iceland, Liechtenstein and Norway.

This approval of Opdivo in combination with cisplatin and gemcitabine based on results of the CheckMate -901 trial, further supports the EU’s previous approval of Opdivo for the adjuvant treatment of adults with muscle-invasive urothelial carcinoma with tumor cell PD-L1 expression ≥1% who are at a high risk of recurrence after undergoing radical resection. In addition to this approved indication in UC, Opdivo-based options are also approved for treatment of 10 different cancer types in the EU including: non-small cell lung cancer (NSCLC), melanoma, esophageal squamous cell carcinoma (ESCC), gastric, gastroesophageal junction (GEJ) or esophageal adenocarcinoma (EAC), esophageal or gastroesophageal junction (GEJ) cancer, colorectal cancer, mesothelioma, renal cell carcinoma, esophageal squamous cell carcinoma (ESCC) and squamous cell cancer of the head and neck.

CheckMate -901 Efficacy and Safety Results

With a median follow up of approximately 33 months of the CheckMate -901 trial, results showed:

OS (overall survival; primary endpoint): Opdivo in combination with cisplatin and gemcitabine reduced the risk of death in patients by 22%, demonstrating a median OS of 21.7 months versus 18.9 months with cisplatin-gemcitabine alone (HR (hazard ratio): 0.78; 95% CI (confidence interval): 0.63, 0.96; p=0.0171).
PFS (progression-free survival; primary endpoint): Risk of disease progression or death reduced by 28%, with a median PFS of 7.9 months compared to 7.6 months with cisplatin-gemcitabine alone (HR 0.72; 95% CI: 0.59, 0.88; p=0.0012).
ORR (overall response rate; secondary endpoint): Opdivo in combination with cisplatin and gemcitabine resulted in an ORR of 57.6% (n=175) (95% CI: 51.8, 63.2) versus 43.1% (n=131) (95% CI: 37.5, 48.9) with cisplatin-gemcitabine alone.
CR (complete response) rate and PR (partial response) rate (secondary endpoints): The CR rate and PR rate seen in patients treated with Opdivo in combination with cisplatin and gemcitabine was 22% (n=66) and 36% (n=109), respectively, versus 12% (n=36) and 31% (n=95) with cisplatin-gemcitabine alone.

About CheckMate -901

CheckMate -901 is a Phase 3, randomized, open-label trial evaluating Opdivo in combination with Yervoy ® (ipilimumab) or Opdivo in combination with cisplatin and gemcitabine followed by Opdivo monotherapy compared to standard-of-care chemotherapy alone, in patients with untreated, unresectable or metastatic urothelial cancer.

In CheckMate -901, evaluating Opdivo with cisplatin and gemcitabine vs. standard-of-care chemotherapy alone, a total of 608 patients eligible for cisplatin-based chemotherapy were randomized to receive either Opdivo 360 mg in combination with cisplatin and gemcitabine every three weeks for up to six cycles followed by 480 mg/Q4 Opdivo monotherapy every 4 weeks until disease progression or death up to a maximum of two years, or cisplatin-gemcitabine alone every three weeks for up to six cycles. The primary endpoints of this study are overall survival (OS) and progression-free survival (PFS).

The OS and PFS outcomes for patients eligible for cisplatin-based chemotherapy are based on the final efficacy analyses of these endpoints.

The CheckMate -901 primary study, evaluating Opdivo plus Yervoy vs. standard-of-care cisplatin- or carboplatin-based chemotherapy in patients with untreated, unresectable or metastatic urothelial carcinoma remains ongoing.

Select Safety Profile from CheckMate -901

Serious adverse reactions occurred in 48% of patients receiving Opdivo with chemotherapy.1 The most frequent serious adverse reactions reported in ≥2% of patients who received Opdivo with chemotherapy were urinary tract infection (4.9%), acute kidney injury (4.3%), anemia (3%), pulmonary embolism (2.6%), sepsis (2.3%), and platelet count decreased (2.3%).1 The most common adverse reactions (reported in ≥20% of patients) were nausea, fatigue, musculoskeletal pain, constipation, decreased appetite, rash, vomiting, and peripheral neuropathy.1 Fatal adverse reactions occurred in 3.6% patients who received Opdivo with chemotherapy; these included sepsis (1%).1 Opdivo and/or chemotherapy were discontinued in 30% of patients and were delayed in 67% of patients for an adverse reaction.

About Urothelial Carcinoma

Bladder cancer is the ninth most common cancer in the world, with more than 600,000 new cases diagnosed annually. Urothelial carcinoma, which most frequently begins in the cells that line the inside of the bladder, accounts for approximately 90% of bladder cancer cases. In addition to the bladder, urothelial carcinoma can occur in other parts of the urinary tract, including the ureters and renal pelvis. The majority of urothelial carcinomas are diagnosed at an early stage, but rates of recurrence and disease progression are high. Approximately 50% of patients who undergo radical surgery will experience disease recurrence, especially within the first two to three years after surgical removal of the bladder or kidney. For patients whose disease recurs as metastatic cancer, the prognosis is poor, with a median overall survival of approximately 12 to 14 months when treated with systemic therapy.

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

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.

INDICATIONS

OPDIVO® (nivolumab), as a single agent, is indicated for the treatment of adult and pediatric patients 12 years and older with unresectable or metastatic melanoma.

OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of adult and pediatric patients 12 years and older with unresectable or metastatic melanoma.

OPDIVO® is indicated for the adjuvant treatment of adult and pediatric patients 12 years and older with completely resected Stage IIB, Stage IIC, Stage III, or Stage IV melanoma.

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), in combination with cisplatin and gemcitabine, is indicated as first-line treatment for adult patients with unresectable or metastatic urothelial carcinoma.

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

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

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

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

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

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

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

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

https://www.opdivo.com/

Please see US Full Prescribing Information for OPDIVO and YERVOY.

Clinical Trials and Patient Populations

Checkmate 227—previously untreated metastatic non-small cell lung cancer, in combination with YERVOY; Checkmate 9LA–previously untreated recurrent or metastatic non-small cell lung cancer in combination with YERVOY and 2 cycles of platinum-doublet chemotherapy by histology; Checkmate 649–previously untreated advanced or metastatic gastric cancer, gastroesophageal junction and esophageal adenocarcinoma; Checkmate 577–adjuvant treatment of esophageal or gastroesophageal junction cancer; Checkmate 238– adjuvant treatment of patients with completely resected Stage III or Stage IV melanoma; Checkmate 76K– adjuvant treatment of patients 12 years of age and older with completely resected Stage IIB or Stage IIC melanoma; Checkmate 274–adjuvant treatment of urothelial carcinoma; Checkmate 275–previously treated advanced or metastatic urothelial carcinoma; Checkmate 142–MSI-H or dMMR metastatic colorectal cancer, as a single agent or in combination with YERVOY; Checkmate 142–MSI-H or dMMR metastatic colorectal cancer, as a single agent or in combination with YERVOY; Attraction-3–esophageal squamous cell carcinoma; Checkmate 648—previously untreated, unresectable advanced recurrent or metastatic esophageal squamous cell carcinoma; Checkmate 648—previously untreated, unresectable advanced recurrent or metastatic esophageal squamous cell carcinoma; Checkmate 040–hepatocellular carcinoma, in combination with YERVOY; Checkmate 743–previously untreated unresectable malignant pleural mesothelioma, in combination with YERVOY; Checkmate 037–previously treated metastatic melanoma; Checkmate 066—previously untreated metastatic melanoma; Checkmate 067–previously untreated metastatic melanoma, as a single agent or in combination with YERVOY; Checkmate 017–second-line treatment of metastatic squamous non-small cell lung cancer; Checkmate 057–second-line treatment of metastatic non-squamous non-small cell lung cancer; Checkmate 816–neoadjuvant non-small cell lung cancer, in combination with platinum-doublet chemotherapy; Checkmate 901–Adult patients with unresectable or metastatic urothelial carcinoma; Checkmate 141–recurrent or metastatic squamous cell carcinoma of the head and neck; Checkmate 025–previously treated renal cell carcinoma; Checkmate 214–previously untreated renal cell carcinoma, in combination with YERVOY; Checkmate 9ER–previously untreated renal cell carcinoma, in combination with cabozantinib; Checkmate 205/039–classical Hodgkin lymphoma.

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

Source: Bristol Myers Squibb

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Bristol-Myers gets EU approval for Opdivo for bladder cancer

May 29, 2024 10:04 AM ET

Bristol-Myers Squibb Company (BMY) Stock

By: Val Brickates Kennedy, SA News Editor6 Comments

Bristol-Myers Squibb (NYSE:BMY) said it has received EU approval for its drug Opdivo as a first-line treatment for adults with unresectable or metastatic urothelial carcinoma, a type of bladder cancer.

The drug was approved for use in combination with cisplatin and gemcitabine, according to the company.

https://seekingalpha.com/news/4111155-bristol-myers-gets-eu-approval-for-opdivo-for-bladder-cancer?mailingid=35532067&messageid=2900&serial=35532067.8065&utm_campaign=rta-stock-news&utm_content=link-1&utm_medium=email&utm_source=seeking_alpha&utm_term=35532067.8065

Bristol-Myers Squibb Company (BMY) Stock

https://www.bms.com/

https://www.opdivo.com/

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

KEYTRUDA® (pembrolizumab)

Merck Announces Phase 3 KEYNOTE-522 Trial Met its Overall Survival (OS) Endpoint in Patients With High-Risk Early-Stage Triple Negative Breast Cancer (TNBC)

May 28, 2024 6:45 am ET

KEYTRUDA® (pembrolizumab) is the first and only immunotherapy-based regimen to show a statistically significant improvement in OS as pre-operative (neoadjuvant) treatment with chemotherapy and then as a single agent after surgery (adjuvant) compared to pre-operative chemotherapy in patients with high-risk early-stage TNBC

New OS results build on the pathological complete response and event-free survival data previously reported from the KEYNOTE-522 trial

RAHWAY, N.J.--(BUSINESS WIRE)-- Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced that the Phase 3 KEYNOTE-522 trial evaluating KEYTRUDA, Merck’s anti-PD-1 therapy, met its overall survival (OS) endpoint, in combination with chemotherapy as pre-operative (neoadjuvant) treatment and then continuing as a single agent after surgery (adjuvant) for the treatment of patients with high-risk early-stage triple-negative breast cancer (TNBC). At a pre-specified interim analysis conducted by an independent Data Monitoring Committee, KEYTRUDA demonstrated a statistically significant and clinically meaningful improvement in OS compared to pre-operative chemotherapy. The safety profile of KEYTRUDA was consistent with that observed in previously reported studies; no new safety signals were observed. Results will be presented at an upcoming medical meeting and shared with regulatory authorities.

“This is a significant milestone, as it is the first time an immunotherapy-based regimen has demonstrated a statistically significant overall survival benefit compared to chemotherapy alone in patients with high-risk early-stage triple-negative breast cancer,” said Dr. Gursel Aktan, vice president, global clinical development, Merck Research Laboratories. “To have achieved overall survival from this landmark study is highly encouraging and builds upon the positive pathological complete response and event-free survival results that led to approvals for this regimen around the world.”

KEYNOTE 522 is the fourth study of a KEYTRUDA-based regimen in an earlier stage of cancer to demonstrate an OS benefit, in addition to KEYNOTE-A18 in cervical cancer, KEYNOTE-671 in non-small cell lung cancer and KEYNOTE-564 in renal cell carcinoma.

In the U.S., KEYTRUDA has two approved indications in TNBC: for the treatment of patients with high-risk early-stage TNBC in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery; and in combination with chemotherapy 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.

Merck has a comprehensive clinical development program in various subtypes of breast cancer. This includes KEYNOTE-242 evaluating KEYTRUDA monotherapy as adjuvant treatment in patients with TNBC who have residual disease; KEYNOTE-756 evaluating KEYTRUDA plus chemotherapy in patients with high-risk, early-stage estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) breast cancer; TroFuse-010 evaluating KEYTRUDA plus sacituzumab tirumotecan (sac-TMT), an investigational trophoblast cell-surface antigen 2 (TROP2)-directed antibody-drug conjugate that Merck is developing in collaboration with Kelun-Biotech, compared to sac-TMT alone and compared to physician’s choice of treatment in patients with unresectable locally advanced or metastatic ER+/HER2- breast cancer; and TroFuse-012 evaluating KEYTRUDA plus sac-TMT versus physician’s choice of treatment in patients with TNBC who received KEYTRUDA-based neoadjuvant therapy and did not achieve a pathological complete response (pCR) at surgery.

About KEYNOTE-522

KEYNOTE-522 (ClinicalTrials.gov, NCT03036488), is a randomized, double-blind Phase 3 trial. The dual primary endpoints were pCR rate, defined as pathological stage ypT0/Tis ypN0 at the time of definitive surgery, and event-free survival, defined as the time from randomization to the time of first occurrence of either disease progression that precluded definitive surgery, a local/distant recurrence, a second primary cancer or death from any cause. A key secondary endpoint was OS. The study enrolled 1,174 patients who were randomized 2:1 to receive either:

The KEYTRUDA regimen: KEYTRUDA plus chemotherapy (paclitaxel and carboplatin), followed by KEYTRUDA plus chemotherapy (cyclophosphamide and either doxorubicin or epirubicin) as neoadjuvant therapy prior to surgery, followed by KEYTRUDA monotherapy as adjuvant therapy post-surgery (n=784) or;
The chemotherapy-placebo regimen: Placebo plus chemotherapy (paclitaxel and carboplatin), followed by placebo plus chemotherapy (cyclophosphamide and either doxorubicin or epirubicin) as neoadjuvant therapy prior to surgery, followed by placebo monotherapy as adjuvant therapy post-surgery (n=390).

About triple-negative breast cancer (TNBC)

Triple-negative breast cancer is the most aggressive type of breast cancer, which has the highest risk of recurrence within the first five years after diagnosis and is associated with worse outcomes compared to other forms of breast cancer. Approximately 10-15% of patients with breast cancer are diagnosed with TNBC. While some breast cancers may test positive for estrogen receptors, progesterone receptors or overexpression of human epidermal growth factor receptor 2 (HER2), TNBC tests negative for all three. Triple-negative breast cancer tends to be more common in people who are younger than 40 years of age, who are Black or who have a BRCA1 mutation.

About Merck’s research in breast and gynecologic cancers

Merck is advancing research aimed at improving outcomes for patients affected by breast and gynecologic (ovarian, cervical and endometrial) cancers. Merck has a comprehensive clinical development program across these cancers comprised of more than 20 Merck-sponsored Phase 3 studies evaluating KEYTRUDA as monotherapy and in combination with other medicines. In the U.S., KEYTRUDA currently has two approved indications for TNBC, including one for high-risk early-stage disease, and five approved indications across certain types of cervical and endometrial cancers (see indications below). Among Merck’s research efforts are trials focused on evaluating KEYTRUDA in earlier stages of these cancers, as well as identifying new combinations and coformulations with KEYTRUDA.

About Merck’s early-stage cancer clinical program

Finding cancer at an earlier stage may give patients a greater chance of long-term survival. Many cancers are considered most treatable and potentially curable in their earliest stage of disease. Building on the strong understanding of the role of KEYTRUDA in later-stage cancers, Merck is evaluating our portfolio of medicines and pipeline candidates in earlier disease states, with more than 30 ongoing registrational studies across multiple types of cancer.

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.

Selected KEYTRUDA® (pembrolizumab) Indications in the U.S.

Triple-Negative Breast Cancer

See additional selected KEYTRUDA indications in the U.S. after the Selected Important Safety Information.

https://www.keytruda.com/

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

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

KEYTRUDA, as a single agent, is indicated as adjuvant treatment following resection and platinum-based chemotherapy for adult patients with Stage IB (T2a ≥4 cm), II, or IIIA NSCLC.

Head and Neck Squamous Cell Cancer

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 Cancer

KEYTRUDA, in combination with enfortumab vedotin, is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma:

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.

Microsatellite Instability-High or Mismatch Repair Deficient Cancer

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

Esophageal Cancer

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 chemoradiotherapy (CRT), is indicated for the treatment of patients with FIGO 2014 Stage III-IVA cervical cancer.

Hepatocellular Carcinoma

KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) secondary to hepatitis B who have received prior systemic therapy other than a PD-1/PD-L1-containing regimen.

Biliary Tract Cancer

KEYTRUDA, in combination with gemcitabine and cisplatin, is indicated for the treatment of patients with locally advanced unresectable or metastatic biliary tract cancer (BTC).

Merkel Cell Carcinoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC).

Renal Cell Carcinoma

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

Endometrial Carcinoma

Tumor Mutational Burden-High Cancer

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.

Merck’s focus on cancer

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 X (formerly 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.

https://seekingalpha.com/symbol/MRK

https://www.merck.com/

https://www.nasdaq.com/market-activity/stocks/mrk

https://www.keytruda.com/

TEZSPIRE® (tezepelumab-ekko)

NEW DATA PRESENTED AT ATS 2024 SHOW THE POTENTIAL OF TEZSPIRE® TO HELP PATIENTS LIVING WITH COPD

Late-Breaking Results From the Phase 2a COURSE Trial Illustrate Tezspire's Impact on COPD Exacerbations in Patients With a Broad Range of Eosinophil Levels

THOUSAND OAKS, Calif., May 19, 2024 /PRNewswire/ -- Amgen (NASDAQ:AMGN) and AstraZeneca today announced the results of the Phase 2a COURSE trial evaluating Tezspire® (tezepelumab-ekko) in people with moderate to very severe chronic obstructive pulmonary disease (COPD) with a broad range of baseline blood eosinophil counts (BEC) irrespective of emphysema, chronic bronchitis or smoking status. The primary results showed that treatment with Tezspire led to a 17% numerical reduction in the annual rate of moderate or severe COPD exacerbations compared to placebo at week 52, which was not statistically significant (90% CI: -6, 36; p[1-sided]=0.1042). The results will be featured in presentations at the American Thoracic Society (ATS) International Conference, May 17-22, in San Diego.

Importantly, this proof-of-concept study showed that, in patients with BEC ≥150 cells/µL, tezepelumab led to a nominally significant reduction of 37% in the rate of moderate or severe exacerbations compared to placebo. Studies suggest that approximately 65% of bio-eligible patients with COPD have a BEC ≥150 cells/μL. Among patients with BEC ≥300 cells/µL, tezepelumab led to a numerical reduction of 46% in the rate of moderate or severe exacerbations (Table 1). Trends towards improved outcomes were also seen with tezepelumab use for pre-bronchodilator FEV1 and SGRQ total score.

"Despite advances in treatments for patients with COPD, there is still a pressing need for effective therapies that can improve their clinical outcome, especially for those with eosinophil counts above 150 cells/µL," said Jay Bradner, M.D., executive vice president of Research and Development and chief scientific officer at Amgen. "We are now actively planning a Phase 3 clinical program evaluating tezepelumab in patients with COPD."

A subgroup analysis of the COURSE trial also showed treatment with tezepelumab resulted in numerical improvements in lung function as measured by forced expiratory volume (FEV1) (improvement of 63 mL and 146 mL in BEC ≥150 and ≥300 cells/μL respectively, compared to placebo) and in quality of life as measured by the St. George's Respiratory Questionnaire (SGRQ) score (reduction of 4.2 points and 9.5 points in BEC ≥150 and ≥300 cells/μL respectively). The safety and tolerability profile for tezepelumab was consistent with its approved severe asthma indication; the most frequently reported (>10%) adverse events for tezepelumab were worsening of COPD (12.1%) and incidents of COVID-19 infections (14.5%) (this trial commenced in July 2019) (Table 2).

"I believe biologics will play a critical role in the future care of COPD, and trials such as the tezepelumab COURSE trial are central to understanding and shaping the treatment landscape," said Dr. Dave Singh, professor of respiratory pharmacology at the University of Manchester and lead investigator on the trial. "The tezepelumab COURSE results are particularly important as they show activity in COPD across a broad patient population including those with baseline blood eosinophil counts greater than 150 cells/μL."

About the COURSE Phase 2a Trial
COURSE was a Phase 2a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial designed to evaluate the safety and efficacy of tezepelumab in adults with moderate to very severe COPD receiving triple inhaled maintenance therapy, and having had two or more documented COPD exacerbations in the 12 months prior to Visit 1. A total of 337 patients were randomized globally, with patients stratified by region and prior number of exacerbations (two vs. three or more). Patients received tezepelumab 420 mg or placebo administered via subcutaneous injection at the trial site every four weeks over a 52-week treatment period. The trial included a post-treatment follow-up period of 12 weeks.

About Chronic Obstructive Pulmonary Disease (COPD)
COPD refers to a group of lung diseases, including chronic bronchitis and emphysema, that cause airflow blockage and breathing-related problems. COPD is a major public health threat that affects an estimated 391 million people around the world, with global costs connected to the disease expected to rise to US $4.8 trillion by 2030. COPD is a highly complex disease with multiple pathways and disease drivers, and a single COPD exacerbation can increase the risk of hospitalization. Baseline blood eosinophil counts are a key factor in how physicians select optimal treatments for COPD. Approximately 65% of patients with COPD who are eligible for biologic treatment have a BEC >150 cells/µL, 20-40% have a BEC >300 cells/µL.

About TEZSPIRE® (tezepelumab-ekko)
TEZSPIRE is a first-in-class human monoclonal antibody that works on the primary source of inflammation: the airway epithelium, which is the first point of contact for viruses, allergens, pollutants and other environmental insults. Specifically, TEZSPIRE targets and blocks thymic stromal lymphopoietin (TSLP), a key epithelial cytokine that sits at the top of multiple inflammatory cascades and initiates an overreactive immune response to allergic, eosinophilic and other types of airway inflammation associated with severe asthma. TSLP is released in response to multiple triggers associated with asthma exacerbations, including allergens, viruses and other airborne particles.

Expression of TSLP is increased in the airways of patients with asthma and has been correlated with disease severity. Blocking TSLP may prevent the release of pro-inflammatory cytokines by immune cells, resulting in the prevention of asthma exacerbations and improved asthma control. By working at the top of the cascade, TEZSPIRE helps stop inflammation at the source and has the potential to treat a broad population of severe asthma patients.

Beyond severe asthma, TEZSPIRE is also in development for other potential indications including chronic obstructive pulmonary disease, chronic rhinosinusitis with nasal polyps, chronic spontaneous urticaria and eosinophilic esophagitis (EoE). In October 2021, tezepelumab was granted Orphan Drug Designation by the FDA for the treatment of EoE.

About the Amgen and AstraZeneca Collaboration
In 2020, Amgen and AstraZeneca updated the 2012 collaboration agreement for TEZSPIRE. Both companies will continue to share costs and profits equally after payment by AstraZeneca of a mid-single-digit royalty to Amgen. AstraZeneca continues to lead development and Amgen continues to lead manufacturing. All aspects of the collaboration are under the oversight of joint governing bodies. Under the amended agreement, Amgen and AstraZeneca will jointly commercialize TEZSPIRE in North America. Amgen will record product sales in the U.S., with AstraZeneca recording its share of U.S. profits as Collaboration Revenue. Outside of the U.S., AstraZeneca will record product sales, with Amgen recording profit share as Other/Collaboration revenue.

TEZSPIRE® (tezepelumab-ekko) U.S. Indication

TEZSPIRE is indicated for the add-on maintenance treatment of adult and pediatric patients aged 12 years and older with severe asthma.

TEZSPIRE is not indicated for the relief of acute bronchospasm or status asthmaticus.

TEZSPIRE® (tezepelumab-ekko) Important Safety Information

https://www.tezspire.com/

Please see the full Prescribing Information including Patient Information and Instructions for Use.

You may report side effects related to AstraZeneca products by clicking here.

About Amgen
Amgen discovers, develops, manufactures and delivers innovative medicines to help millions of patients in their fight against some of the world's toughest diseases. More than 40 years ago, Amgen helped to establish the biotechnology industry and remains on the cutting-edge of innovation, using technology and human genetic data to push beyond what's known today. Amgen is advancing a broad and deep pipeline that builds on its existing portfolio of medicines to treat cancer, heart disease, osteoporosis, inflammatory diseases and rare diseases.

For more information, visit Amgen.com and follow Amgen on X, LinkedIn, Instagram, TikTok, YouTube and Threads.

Amgen Logo. (PRNewsFoto/Amgen) (PRNewsFoto/)

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SOURCE Amgen

AstraZeneca, Amgen release mid-stage data on Tezspire for COPD

May 20, 2024 12:49 PM ET

AstraZeneca PLC (AZN) Stock, AMGN Stock

By: Jonathan Block, SA News Editor

AstraZeneca (NASDAQ:AZN) and Amgen (NASDAQ:AMGN) said that phase 2a data on their asthma biologic Tezspire (tezepelumab) indicates the treatment may be effective in treating chronic obstructive pulmonary disease (COPD).
Though not statistically significant, data from the COURSE trial showed patients on Tezspire saw a 17% reduction in the annual rate of moderate or severe COPD exacerbations compared to placebo after a year.
https://seekingalpha.com/news/4108441-astrazeneca-amgen-release-mid-stage-data-tezspire-copd?mailingid=35440221&messageid=2900&serial=35440221.2605&utm_campaign=rta-stock-news&utm_content=link-1&utm_medium=email&utm_source=seeking_alpha&utm_term=35440221.2605
AstraZeneca PLC (AZN) Stock, AMGN Stock
https://www.astrazeneca.com/
https://www.tezspire.com/

APPROVED USE TEZSPIRE is a prescription medicine used with other asthma medicines for the maintenance treatment of severe asthma in people 12 years of age and older whose asthma is not controlled with their current asthma medicine. TEZSPIRE helps prevent severe asthma attacks (exacerbations) and can improve your breathing. TEZSPIRE is not used to treat sudden breathing problems. Tell your healthcare provider if your asthma does not get better or if it gets worse after you start treatment with TEZSPIRE. It is not known if TEZSPIRE is safe and effective in children under 12 years of age.

biotecMAX™ 2024 Insight

Breyanzi ® (lisocabtagene maraleucel; liso-cel)

Bristol Myers Squibb’s CAR T Cell Therapy Breyanzi Approved by the U.S. Food and Drug Administration for Relapsed or Refractory Follicular Lymphoma

05/15/2024CATEGORY:

Corporate/Financial News

FL INFOGRAPHIC UNDERSTANDING THE CAR T CELL THERAPY TREATMENT EXPERIENCE

95.7% of patients responded to Breyanzi in the TRANSCEND FL trial

Breyanzi provided sustained clinical benefit with median duration of response not reached and the majority (77.1%) of responders in ongoing response at 18 months

Breyanzi is a personalized therapy with a differentiated profile, offering durable responses and a consistent safety profile across trials

PRINCETON, N.J.--(BUSINESS WIRE)-- Bristol Myers Squibb (NYSE: BMY) today announced the U.S. Food and Drug Administration (FDA) has granted accelerated approval for Breyanzi ® (lisocabtagene maraleucel; liso-cel), a CD19-directed chimeric antigen receptor (CAR) T cell therapy, for the treatment of adult patients with relapsed or refractory follicular lymphoma (FL) who have received two or more prior lines of systemic therapy. This indication is approved under accelerated approval based on response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s). Breyanzi is also now included in the National Comprehensive Cancer Network (NCCN®) Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for B-cell Lymphomas as a Category 2A recommendation for third-line and subsequent therapy for relapsed or refractory FL.*

Product image for download (Photo: Bristol Myers Squibb)

In relapsed or refractory FL, Breyanzi is delivered as a one-time infusion** with a single dose containing 90 to 110 x 106 CAR-positive viable T cells. Please see the Important Safety Information section below, including Boxed WARNINGS for Breyanzi regarding Cytokine Release Syndrome (CRS), Neurologic Toxicities, and Secondary Hematological Malignancies.

“Breyanzi is a cornerstone of our cell therapy portfolio, providing a differentiated profile across a wide array of B-cell malignancies,” said Bryan Campbell, senior vice president, Head of Commercial, Cell Therapy, Bristol Myers Squibb. “Today’s approval of Breyanzi for relapsed or refractory FL provides an option with potential for lasting remission in a one-time infusion and a safety profile that allows for administration and monitoring in both the inpatient and outpatient setting in an increasing number of certified treatment centers in the U.S.”

Historically, FL has been considered an incurable disease, and patients frequently relapse following front-line therapy, with prognosis worsening after each subsequent relapse. Despite advances in treatment, there remains an unmet need for additional options that offer treatment-free intervals with durable, complete responses.

The Phase 2 TRANSCEND FL study included the largest primary analysis set of patients with relapsed or refractory FL of a clinical trial evaluating a CAR T cell therapy in this patient population. Based on the U.S. Prescribing Information (USPI), in patients treated with Breyanzi in the third-line plus setting and included in the primary efficacy analysis set (n=94), the overall response rate (ORR) was 95.7% (95% CI: 89.5-98.8). ORR was defined as the percentage of patients achieving a partial or complete response per Lugano criteria as assessed by an Independent Review Committee (IRC). The complete response (CR) rate was 73.4% (95% CI: 63.3-82.0) and required a negative bone marrow biopsy for confirmation. Responses were rapid and durable with a median time to response of one month (range: 0.6-3.3) and median duration of response (DOR) not reached (95% CI: 18.04-NR), with 80.9% of responders remaining in response at 12 months, and 77.1% of responders remaining in response at 18 months. Results from the primary analysis of TRANSCEND FL presented at the 2023 International Conference on Malignant Lymphoma showed an ORR of 97% (95% CI: 91.6-99.4; one-sided p<0.0001) in efficacy evaluable patients (n=101), with 94% of patients achieving a CR (95% CI: 87.5-97.8; one-sided p<0.0001).

“In the treatment of relapsed or refractory follicular lymphoma, patients often cycle through treatments with typically shorter responses with each new line of therapy. Those who have experienced early disease progression have notably poor prognosis,” said M. Lia Palomba, M.D., TRANSCEND investigator and lymphoma and cell therapy specialist, Memorial Sloan Kettering Cancer Center. “The FDA approval of liso-cel for patients with relapsed or refractory FL is an important advancement in addressing an ongoing unmet need in the FL treatment paradigm, providing patients a new option that has shown remarkably high response rates and an established safety profile.”

Breyanzi has exhibited a consistent safety profile and across clinical trials, any grade cytokine release syndrome (CRS) occurred in 53% of patients, including Grade >3 CRS in 4% of patients. The median time to onset was 5 days (range: 1 to 63 days). Any grade neurologic events (NEs) occurred in 31% of patients, with Grade >3 NEs occurring in 10% of patients. The median time to onset of NEs was 8 days (range: 1 to 63 days). The safety profile of Breyanzi allows for the option of outpatient treatment and management of patients. Patients in the TRANSCEND FL study were treated in the inpatient and outpatient setting.

“The lymphoma community has felt an urgent need for advancements in the treatment of relapsed or refractory follicular lymphoma,” said Meghan Gutierrez, chief executive officer, Lymphoma Research Foundation. “The approval of Breyanzi offers patients a new and meaningful treatment option that provides hope for lasting remission, and we are grateful to those who have contributed to this exciting milestone for patients.”

Bristol Myers Squibb offers various programs and resources to address the needs of patients and caregivers, and provides support that allows for access to therapies, including Breyanzi. Bristol Myers Squibb also supports the patient and physician treatment experience by providing Cell Therapy 360, a digital service platform, which optimizes access to relevant information, manufacturing updates, and patient and caregiver support.

*NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

**Treatment process includes leukapheresis, manufacturing, administration, and adverse event monitoring.

About TRANSCEND FL

TRANSCEND FL (NCT04245839) is an open-label, global, multicenter, Phase 2, single-arm study to determine the efficacy and safety of Breyanzi in patients with relapsed or refractory indolent B-cell non-Hodgkin lymphoma, including follicular lymphoma. The primary outcome measure is overall response rate, including best overall response of complete response or partial response as determined by an Independent Review Committee. Secondary outcome measures include complete response rate, duration of response, progression-free survival, and safety.

About FL

Follicular lymphoma (FL) is the second most common form of non-Hodgkin lymphoma (NHL) and the most common subtype of indolent NHL, accounting for 20 to 30 percent of all NHL cases. The average age of diagnosis for FL is 65 years of age. FL develops when white blood cells cluster together to form lumps in a person’s lymph nodes or organs. It is characterized by periods of remission and relapse, and the disease becomes more difficult to treat after relapse or disease progression.

About Breyanzi

Breyanzi is a CD19-directed CAR T cell therapy with a 4-1BB costimulatory domain, which enhances the expansion and persistence of the CAR T cells. Breyanzi is made from a patient’s own T cells, which are collected and genetically reengineered to become CAR T cells that are then delivered via infusion as a one-time treatment.

Breyanzi is approved in the U.S. for the treatment of relapsed or refractory large B-cell lymphoma (LBCL) after at least one prior line of therapy and received accelerated approval for the treatment of relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma after at least two prior lines of therapy. Breyanzi is also approved in Japan, the European Union (EU), and Switzerland for the second-line treatment or relapsed or refractory LBCL, and in Japan, the European Union, Switzerland, the UK and Canada for relapsed and refractory LBCL after two or more lines of systemic therapy.

Bristol Myers Squibb’s clinical development program for Breyanzi includes clinical studies in other types of lymphoma. For more information, visit clinicaltrials.gov.

Indication

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

adult patients with large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B, who have:
- refractory disease to first-line chemoimmunotherapy or relapse within 12 months of first-line chemoimmunotherapy; or
- refractory disease to first-line chemoimmunotherapy or relapse after first-line chemoimmunotherapy and are not eligible for hematopoietic stem cell transplantation (HSCT) due to comorbidities or age; or
- relapsed or refractory disease after two or more lines of systemic therapy.

Limitations of Use: BREYANZI is not indicated for the treatment of patients with primary central nervous system lymphoma.

Adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have received at least 2 prior lines of therapy, including a Bruton tyrosine kinase (BTK) inhibitor and a B-cell lymphoma 2 (BCL-2) inhibitor. This indication is approved under accelerated approval based on response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
Adult patients with relapsed or refractory follicular lymphoma (FL) who have received 2 or more prior lines of systemic therapy. This indication is approved under accelerated approval based on response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
https://www.breyanzi.com/

Please see full Prescribing Information , including Boxed WARNINGS and Medication Guide .

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

Learn more about the science behind cell therapy and ongoing research at Bristol Myers Squibb here.

About Bristol Myers Squibb

Source: Bristol Myers Squibb

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Bristol Myers' Breyanzi gains additional indication for follicular lymphoma

May 15, 2024 5:36 PM ET

Bristol-Myers Squibb Company (BMY) StockFL

By: Jonathan Block, SA News Editor

The U.S. FDA has granted accelerated approval to Bristol-Myers Squibb's (NYSE:BMY) gene therapy Breyanzi (lisocabtagene maraleucel) for follicular lymphoma in patients who have received at least two prior lines of therapy, Bloomberg reported.
https://seekingalpha.com/news/4107041-bristol-myers-squibb-breyanzi-gains-additional-indication-follicular-lymphoma
Bristol-Myers Squibb Company (BMY) Stock
https://www.bms.com/
https://www.breyanzi.com/

Indication BREYANZI is a prescription medicine used to treat two types of non-Hodgkin lymphoma: Large B cell lymphoma, when: your first treatment has not worked or your cancer returned within a year of your first treatment OR your first treatment has not worked or your cancer returned after the first treatment, and you are not eligible for hematopoietic stem cell transplantation because of medical conditions or age OR two or more kinds of treatment have not worked or stopped working. Chronic lymphocytic leukemia or small lymphocytic lymphoma when two or more kinds of treatment have not worked or stopped working. BREYANZI is different than other cancer medicines because it is made from your own white blood cells, which have been genetically modified to recognize and attack your lymphoma cells.

Opdivo (nivolumab) Plus Yervoy (ipilimumab)

European Medicines Agency Validates Bristol Myers Squibb’s Application for Opdivo (nivolumab) Plus Yervoy (ipilimumab) for the First-Line Treatment of Adult Patients with Microsatellite...

05/06/2024CATEGORY:

Corporate/Financial News

Application based on results from the CheckMate -8HW study, in which Opdivo plus Yervoy demonstrated statistically significant and clinically meaningful improvement in progression-free survival compared to investigator’s choice of chemotherapy

PRINCETON, N.J.--(BUSINESS WIRE)--

European Medicines Agency Validates Bristol Myers Squibb’s Application for Opdivo (nivolumab) Plus Yervoy (ipilimumab) for the First-Line Treatment of Adult Patients with Microsatellite Instability–High or Mismatch Repair Deficient Metastatic Colorectal Cancer

Bristol Myers Squibb (NYSE: BMY) today announced that the European Medicines Agency (EMA) has validated its Type II variation application for Opdivo® (nivolumab) plus Yervoy ® (ipilimumab) for the first-line treatment of adult patients with microsatellite instability–high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (mCRC). The EMA’s validation of the application confirms the submission is complete and begins the EMA’s centralized review process.

“Colorectal cancer is the third most commonly diagnosed cancer in the world, and more options are needed specifically for patients with MSI-H/dMMR mCRC, who are less likely to benefit from treatment with chemotherapy,” said Dana Walker, M.D., M.S.C.E., vice president, global program lead, gastrointestinal and genitourinary cancers, Bristol Myers Squibb. “We look forward to working with the European Medicines Agency to discuss bringing the dual immunotherapy combination of Opdivo and Yervoy to patients with MSI-H/dMMR mCRC across Europe.”

The submission is based on results from the CheckMate -8HW study, in which Opdivo plus Yervoy demonstrated a statistically significant and clinically meaningful improvement in the dual primary endpoint of progression-free survival (PFS) compared to investigator’s choice of chemotherapy as assessed by Blinded Independent Clinical Review (BICR) for the first-line treatment of patients with MSI-H/dMMR mCRC. These data from CheckMate -8HW were presented at the 2024 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium. The study is ongoing to assess the other dual primary endpoint of PFS in patients receiving Opdivo plus Yervoy compared to Opdivo alone, as well as secondary endpoints. The safety profile for the dual immunotherapy combination remained consistent with previously reported data and was manageable with established protocols, with no new safety signals identified.

Bristol Myers Squibb thanks the patients and investigators involved in the CheckMate -8HW clinical trial.

About CheckMate -8HW

CheckMate -8HW (NCT04008030) is a Phase 3 randomized, open-label trial evaluating Opdivo plus Yervoy compared to Opdivo alone or investigator’s choice chemotherapy (mFOLFOX-6 or FOLFIRI with or without bevacizumab or cetuximab) in patients with microsatellite instability–high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (mCRC).

Approximately 830 patients were randomized to receive either Opdivo monotherapy (Opdivo 240 mg Q2W for six doses, followed by Opdivo 480 mg Q4W), Opdivo plus Yervoy (Opdivo 240 mg plus Yervoy 1 mg/kg Q3W for four doses, followed by Opdivo 480 mg Q4W), or investigator’s choice of chemotherapy. The dual primary endpoints of the trial are progression-free survival (PFS) per blinded independent central review (BICR) for Opdivo plus Yervoy compared to investigator’s choice of chemotherapy in the first line setting and PFS per BICR for Opdivo plus Yervoy compared to Opdivo alone across all lines of therapy. The trial also includes several secondary safety and efficacy endpoints, including overall survival (OS).

The study is ongoing to assess the second dual primary endpoint of PFS in patients receiving Opdivo plus Yervoy compared to Opdivo alone across all lines of therapy, as well as secondary endpoints.

About dMMR or MSI-H Colorectal Cancer

Colorectal cancer (CRC) is cancer that develops in the colon or the rectum, which are part of the body’s digestive or gastrointestinal system. CRC is the third most commonly diagnosed cancer in the world. In 2020, it is estimated that there were approximately 1,931,000 new cases of the disease; it is the second leading cause of cancer-related deaths among men and women combined.

Mismatch repair deficiency (dMMR) occurs when the proteins that repair mismatch errors in DNA replication are missing or non-functional, leading to microsatellite instability-high (MSI-H) tumors. Approximately 5-7% of metastatic CRC patients have dMMR or MSI-H tumors; they are less likely to benefit from conventional chemotherapy and typically have a poor prognosis.

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

About Opdivo

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.

About Yervoy

Yervoy is a recombinant, human monoclonal antibody that binds to the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4). CTLA-4 is a negative regulator of T-cell activity. Yervoy binds to CTLA-4 and blocks the interaction of CTLA-4 with its ligands, CD80/CD86. Blockade of CTLA-4 has been shown to augment T-cell activation and proliferation, including the activation and proliferation of tumor infiltrating T-effector cells. Inhibition of CTLA-4 signaling can also reduce T-regulatory cell function, which may contribute to a general increase in T-cell responsiveness, including the anti-tumor immune response. On March 25, 2011, the U.S. Food and Drug Administration (FDA) approved Yervoy 3 mg/kg monotherapy for patients with unresectable or metastatic melanoma. Yervoy is approved for unresectable or metastatic melanoma in more than 50 countries. There is a broad, ongoing development program in place for Yervoy spanning multiple tumor types.