On June 25, 2021 Bristol Myers Squibb (NYSE: BMY) reported the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended granting Conditional Marketing Authorization for Abecma (idecabtagene vicleucel; ide-cel), the company’s B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T cell immunotherapy, for the treatment of adult patients with relapsed and refractory multiple myeloma who have received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody and have demonstrated disease progression on the last therapy (Press release, Bristol-Myers Squibb, JUN 25, 2021, View Source [SID1234584369]). The CHMP recommendation will now be reviewed by the European Commission (EC), which has the authority to approve medicines for the European Union (EU).

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The CHMP adopted a positive opinion based on results from the pivotal Phase 2 KarMMa study evaluating the efficacy and safety of Abecma in 128 patients with heavily pre-treated and highly refractory multiple myeloma.

"As the first CAR T cell therapy for relapsed and refractory multiple myeloma to receive a positive CHMP opinion, Abecma represents a potential new treatment approach for patients in Europe battling this incurable blood cancer," said Noah Berkowitz, M.D., Ph.D., senior vice president, Cellular Therapy Development, Bristol Myers Squibb. "We look forward to the European Commission’s decision as we build on our innovative multiple myeloma and cell therapy research to offer novel and personalized treatment options for patients in need."

The EC is expected to deliver its final decision within 67 days of receipt of the CHMP opinion. The decision will be applicable to all European Union member states and Iceland, Norway and Liechtenstein. The EMA previously granted Abecma access to the PRIority MEdicines (PRIME) scheme for the treatment of relapsed and refractory multiple myeloma.

About KarMMa

KarMMa (NCT03361748) is a pivotal, open-label, single-arm, multicenter, multinational, Phase 2 study evaluating the efficacy and safety of ide-cel in adults with relapsed and refractory multiple myeloma in North America and Europe. The primary endpoint of the study is overall response rate as assessed by an independent review committee (IRC) according to the International Myeloma Working Group (IMWG) criteria. Complete response rate is a key secondary endpoint. Other secondary endpoints include time to response, duration of response, progression-free survival, overall survival, minimal residual disease evaluated by Next-Generation Sequencing (NGS) assay and safety. The study enrolled 140 patients, of whom 128 received ide-cel across the target dose levels of 150-450 x 106 CAR+ T cells after receiving lymphodepleting chemotherapy. All enrolled patients had received at least three prior treatment regimens, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody, and were refractory to their last regimen, defined as progression during or within 60 days of their last therapy.

About Multiple Myeloma

Multiple myeloma is a cancer of plasma cells in the bone marrow.1 The exact cause of multiple myeloma is not known and currently there is no cure, however, there are a number of treatment options available to help manage the disease.1 Patients who have already been treated with some available therapies but continue to have progression of their disease have "relapsed" and "refractory" multiple myeloma, meaning their cancer has returned after they have received initial treatments.2

About Abecma

Abecma is the first-in-class B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T cell immunotherapy, approved in the U.S. for the treatment of adult patients with relapsed or refractory multiple myeloma after four or more prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. Abecma recognizes and binds to BCMA on the surface of multiple myeloma cells leading to CAR T cell proliferation, cytokine secretion, and subsequent cytolytic killing of BCMA-expressing cells.

Abecma is being jointly developed and commercialized in the U.S. as part of a Co-Development, Co-Promotion, and Profit Share Agreement with Bristol Myers Squibb and bluebird bio. Bristol Myers Squibb will assume sole responsibility for Abecma drug product manufacturing and commercialization outside of the U.S.

U.S. FDA-Approved Indication

ABECMA (idecabtagene vicleucel) is a B-cell maturation antigen (BCMA)-directed genetically modified autologous T cell immunotherapy indicated for the treatment of adult patients with relapsed or refractory multiple myeloma after four or more prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody.

U.S. Important Safety Information

BOXED WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC TOXICITIES, HLH/MAS, AND PROLONGED CYTOPENIA

Cytokine Release Syndrome (CRS), including fatal or life-threatening reactions, occurred in patients following treatment with ABECMA. Do not administer ABECMA to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids.
Neurologic Toxicities, which may be severe or life-threatening, occurred following treatment with ABECMA, including concurrently with CRS, after CRS resolution, or in the absence of CRS. Monitor for neurologic events after treatment with ABECMA. Provide supportive care and/or corticosteroids as needed.
Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS) including fatal and life-threatening reactions, occurred in patients following treatment with ABECMA. HLH/MAS can occur with CRS or neurologic toxicities.
Prolonged Cytopenia with bleeding and infection, including fatal outcomes following stem cell transplantation for hematopoietic recovery, occurred following treatment with ABECMA.
ABECMA is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the ABECMA REMS.
Cytokine Release Syndrome (CRS): CRS, including fatal or life-threatening reactions, occurred following treatment with ABECMA. CRS occurred in 85% (108/127) of patients receiving ABECMA. Grade 3 or higher CRS (Lee grading system) occurred in 9% (12/127) of patients, with Grade 5 CRS reported in one (0.8%) patient. The median time to onset of CRS, any grade, was 1 day (range: 1 – 23 days) and the median duration of CRS was 7 days (range: 1 – 63 days) in all patients including the patient who died. The most common manifestations of CRS included pyrexia (98%), hypotension (41%), tachycardia (35%), chills (31%), hypoxia (20%), fatigue (12%), and headache (10%). Grade 3 or higher events that may be associated with CRS include hypotension, hypoxia, hyperbilirubinemia, hypofibrinogenemia, acute respiratory distress syndrome (ARDS), atrial fibrillation, hepatocellular injury, metabolic acidosis, pulmonary edema, multiple organ dysfunction syndrome and HLH/MAS.

Identify CRS based on clinical presentation. Evaluate for and treat other causes of fever, hypoxia, and hypotension. CRS has been reported to be associated with findings of HLH/MAS, and the physiology of the syndromes may overlap. HLH/MAS is a potentially life-threatening condition. In patients with progressive symptoms of CRS or refractory CRS despite treatment, evaluate for evidence of HLH/MAS.

Fifty four percent (68/127) of patients received tocilizumab; 35% (45/127) received a single dose while 18% (23/127) received more than 1 dose of tocilizumab. Overall, across the dose levels, 15% (19/127) of patients received at least 1 dose of corticosteroids for treatment of CRS. All patients that received corticosteroids for CRS received tocilizumab.

Overall rate of CRS was 79% and rate of Grade 2 CRS was 23% in patients treated in the 300 x 106 CAR+ T cell dose cohort. For patients treated in the 450 x 106 CAR+ T cell dose cohort, the overall rate of CRS was 96% and rate of Grade 2 CRS was 40%. Rate of Grade 3 or higher CRS was similar across the dose range. The median duration of CRS for the 450 x 106 CAR+ T cell dose cohort was 7 days (range: 1-63 days) and for the 300 x 106 CAR+ T cell dose cohort was 6 days (range: 2-28 days). In the 450 x 106 CAR+ T cell dose cohort, 68% (36/53) of patients received tocilizumab and 23% (12/53) received at least 1 dose of corticosteroids for treatment of CRS. In the 300 x 106 CAR+ T cell dose cohort, 44% (31/70) of patients received tocilizumab and 10% (7/70) received corticosteroids. All patients that received corticosteroids for CRS also received tocilizumab. Ensure that a minimum of 2 doses of tocilizumab are available prior to infusion of ABECMA.

Monitor patients at least daily for 7 days following ABECMA infusion at the REMS-certified healthcare facility for signs and symptoms of CRS. Monitor patients for signs or symptoms of CRS for at least 4 weeks after infusion. At the first sign of CRS, institute treatment with supportive care, tocilizumab and/or corticosteroids as indicated.

Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time.

Neurologic Toxicities: Neurologic toxicities, which may be severe or life-threatening, occurred following treatment with ABECMA, including concurrently with CRS, after CRS resolution, or in the absence of CRS. CAR T cell-associated neurotoxicity occurred in 28% (36/127) of patients receiving ABECMA, including Grade 3 in 4% (5/127) of patients. One patient had ongoing Grade 2 neurotoxicity at the time of death. Two patients had ongoing Grade 1 tremor at the time of data cutoff. The median time to onset of neurotoxicity was 2 days (range: 1 – 42 days). CAR T cell-associated neurotoxicity resolved in 92% (33/36) of patients with a median duration of neurotoxicity was 5 days (range: 1 – 61 days). The median duration of neurotoxicity was 6 days (range: 1 – 578) in all patients including those with ongoing neurotoxicity at the time of death or data cut off. Thirty-four patients with neurotoxicity had CRS. Neurotoxicity had onset in 3 patients before, 29 patients during, and 2 patients after CRS. The rate of Grade 3 neurotoxicity was 8% in the 450 x 106 CAR+ T cell dose cohort and 1.4% in the 300 x 106 CAR+ T cell dose cohort. The most frequently reported (greater than or equal to 5%) manifestations of CAR T cell-associated neurotoxicity include encephalopathy (20%), tremor (9%), aphasia (7%), and delirium (6%). Grade 4 neurotoxicity and cerebral edema in 1 patient has been reported with ABECMA in another study in multiple myeloma. Grade 3 myelitis and Grade 3 parkinsonism have been reported after treatment with ABECMA in another study in multiple myeloma.

Monitor patients at least daily for 7 days following ABECMA infusion at the REMS-certified healthcare facility for signs and symptoms of neurologic toxicities. Rule out other causes of neurologic symptoms. Monitor patients for signs or symptoms of neurologic toxicities for at least 4 weeks after infusion and treat promptly. Neurologic toxicity should be managed with supportive care and/or corticosteroids as needed.

Counsel patients to seek immediate medical attention should signs or symptoms of neurologic toxicity occur at any time.

Hemophagocytic Lymphohistiocytosis (HLH)/Macrophage Activation Syndrome (MAS): HLH/MAS occurred in 4% (5/127) of patients receiving ABECMA. One patient treated in the 300 x 106 CAR+ T cell dose cohort developed fatal multi-organ HLH/MAS with CRS. In another patient with fatal bronchopulmonary aspergillosis, HLH/MAS was contributory to the fatal outcome. Three cases of Grade 2 HLH/MAS resolved. The rate of HLH/MAS was 8% in the 450 x 106 CAR+ T cell dose cohort and 1% in the 300 x 106 CAR+ T cell dose cohort. All events of HLH/MAS had onset within 10 days of receiving ABECMA with a median onset of 7 days (range: 4-9 days) and occurred in the setting of ongoing or worsening CRS. Two patients with HLH/MAS had overlapping neurotoxicity. The manifestations of HLH/MAS include hypotension, hypoxia, multiple organ dysfunction, renal dysfunction, and cytopenia. HLH/MAS is a potentially life-threatening condition with a high mortality rate if not recognized early and treated. Treatment of HLH/MAS should be administered per institutional standards.

ABECMA REMS: Due to the risk of CRS and neurologic toxicities, ABECMA is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the ABECMA REMS. Further information is available at www.AbecmaREMS.com or 1-888-423-5436.

Hypersensitivity Reactions: Allergic reactions may occur with the infusion of ABECMA. Serious hypersensitivity reactions, including anaphylaxis, may be due to dimethyl sulfoxide (DMSO) in ABECMA.

Infections: ABECMA should not be administered to patients with active infections or inflammatory disorders. Severe, life-threatening, or fatal infections occurred in patients after ABECMA infusion. Infections (all grades) occurred in 70% of patients. Grade 3 or 4 infections occurred in 23% of patients. Overall, 4 patients had Grade 5 infections (3%); 2 patients (1.6%) had Grade 5 events of pneumonia, 1 patient (0.8%) had Grade 5 bronchopulmonary aspergillosis, and 1 patient (0.8%) had cytomegalovirus (CMV) pneumonia associated with Pneumocystis jirovecii. Monitor patients for signs and symptoms of infection before and after ABECMA infusion and treat appropriately. Administer prophylactic, preemptive, and/or therapeutic antimicrobials according to standard institutional guidelines.

Febrile neutropenia was observed in 16% (20/127) of patients after ABECMA infusion and may be concurrent with CRS. In the event of febrile neutropenia, evaluate for infection and manage with broad spectrum antibiotics, fluids, and other supportive care as medically indicated.

Viral Reactivation: Cytomegalovirus (CMV) infection resulting in pneumonia and death has occurred following ABECMA administration. Monitor and treat for CMV reactivation in accordance with clinical guidelines. Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death, can occur in patients treated with drugs directed against plasma cells. Perform screening for CMV, HBV, hepatitis C virus (HCV), and human immunodeficiency virus (HIV) in accordance with clinical guidelines before collection of cells for manufacturing.

Prolonged Cytopenias: Patients may exhibit prolonged cytopenias following lymphodepleting chemotherapy and ABECMA infusion. In the KarMMa study, 41% of patients (52/127) experienced prolonged Grade 3 or 4 neutropenia and 49% (62/127) experienced prolonged Grade 3 or 4 thrombocytopenia that had not resolved by Month 1 following ABECMA infusion. Rate of prolonged neutropenia was 49% in the 450 x 106 CAR+ T cell dose cohort and 34% in the 300 x 106 CAR+ T cell dose cohort. In 83% (43/52) of patients who recovered from Grade 3 or 4 neutropenia after Month 1, the median time to recovery from ABECMA infusion was 1.9 months. In 65% (40/62) of patients who recovered from Grade 3 or 4 thrombocytopenia, the median time to recovery was 2.1 months. Median time to cytopenia recovery was similar across the 300 and 450 x 106 dose cohort.

Three patients underwent stem cell therapy for hematopoietic reconstitution due to prolonged cytopenia. Two of the three patients died from complications of prolonged cytopenia. Monitor blood counts prior to and after ABECMA infusion. Manage cytopenia with myeloid growth factor and blood product transfusion support according to institutional guidelines.

Hypogammaglobulinemia: Plasma cell aplasia and hypogammaglobulinemia can occur in patients receiving treatment with ABECMA. Hypogammaglobulinemia was reported as an adverse event in 21% (27/127) of patients; laboratory IgG levels fell below 500 mg/dl after infusion in 25% (32/127) of patients treated with ABECMA.

Monitor immunoglobulin levels after treatment with ABECMA and administer IVIG for IgG <400 mg/dl. Manage per local institutional guidelines, including infection precautions and antibiotic or antiviral prophylaxis.

The safety of immunization with live viral vaccines during or following ABECMA treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during ABECMA treatment, and until immune recovery following treatment with ABECMA.

Secondary Malignancies: Patients treated with ABECMA may develop secondary malignancies. Monitor life-long for secondary malignancies. If a secondary malignancy occurs, contact Bristol Myers Squibb at 1-888-805-4555 to obtain instructions on patient samples to collect for testing of secondary malignancy of T cell origin.

Effects on Ability to Drive and Operate Machinery: Due to the potential for neurologic events, including altered mental status or seizures, patients receiving ABECMA are at risk for altered or decreased consciousness or coordination in the 8 weeks following ABECMA infusion. Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, during this initial period.

Adverse Reactions: The most common nonlaboratory adverse reactions (incidence greater than or equal to 20%) include CRS, infections – pathogen unspecified, fatigue, musculoskeletal pain, hypogammaglobulinemia, diarrhea, upper respiratory tract infection, nausea, viral infections, encephalopathy, edema, pyrexia, cough, headache, and decreased appetite.

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

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

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

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

On June 25, 2021 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) and Sanofi reported that the European Commission (EC) has approved the PD-1 inhibitor Libtayo (cemiplimab) to treat adults with locally advanced or metastatic basal cell carcinoma (BCC) who have progressed on or are intolerant to a hedgehog pathway inhibitor (HHI) (Press release, Regeneron, JUN 25, 2021, View Source [SID1234584366]).

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BCC is the most common type of skin cancer worldwide, representing up to 80% of non-melanoma skin cancers, and incidence is increasing across many European countries. While the large majority of BCCs are caught early and easily cured with surgery and/or radiation, a small proportion of cases can develop into advanced BCC and penetrate deeper into surrounding tissues (locally advanced) or spread to other parts of the body (metastatic), becoming more difficult to treat.

"Libtayo is the first immunotherapy to show a clinical benefit in patients with advanced BCC after HHI therapy in a pivotal trial, and with this first-in-class approval has the potential to transform treatment for patients in Europe whose cancer has progressed despite HHI treatment," said Israel Lowy, M.D., Ph.D., Senior Vice President, Translational and Clinical Sciences, Oncology at Regeneron. "We look forward to continuing to investigate this medicine in additional settings, with the goal of helping more patients with difficult-to-treat cancers around the world."

Libtayo is now approved for three advanced cancers in the European Union, following the EC’s concurrent approval of Libtayo for the first-line treatment of adult patients with advanced non-small cell lung cancer (NSCLC) whose tumor cells have ≥50% PD-L1 expression and no EGFR, ALK or ROS1 aberrations. In 2019, Libtayo was approved by the EC as the first treatment for adults with metastatic or locally advanced cutaneous squamous cell carcinoma (CSCC) who are not candidates for curative surgery or curative radiation. Across all of its approved indications, Libtayo had a generally consistent safety profile. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue during or after treatment with Libtayo.

The EC approval in BCC is based on data from the largest prospective clinical trial (n=119) in patients with advanced BCC previously treated with an HHI to date. Libtayo-treated patients with locally advanced BCC experienced an objective response rate (ORR) of 32% (95% confidence interval [CI]: 22-43) (25% partial response, 7% complete response) by independent central review. Libtayo-treated patients with metastatic BCC demonstrated an ORR of 29% (95% CI: 15-46) (26% partial response, 3% complete response) by investigator assessment. In addition, approximately 90% of patients across both groups had a duration of response (DOR) of 6 months or longer per Kaplan Meier estimates, and the median DOR has not been reached for either group. Median duration of follow-up was 16 months for locally advanced BCC and 9 months for metastatic BCC.

Safety was assessed in 816 patients across all four Libtayo monotherapy pivotal trials in its approved indications. Adverse events were serious in 30% of patients and led to permanent discontinuation in 8% of patients. Immune–related adverse reactions occurred in 22% of patients and led to permanent discontinuation in 4% of patients. The most common immune-related adverse reactions were hypothyroidism (8%), hyperthyroidism (3%), pneumonitis (3%), hepatitis (2%), colitis (2%) and immune-related skin adverse reactions (2%).

"Since its launch in Europe just two years ago, Libtayo has redefined the standard of care for advanced CSCC and has the potential to do the same in advanced BCC," said Peter C. Adamson, M.D., Global Development Head, Oncology at Sanofi. "Together with Regeneron, we’re committed to addressing gaps in the treatment of advanced forms of non-melanoma skin cancer."

About the Phase 2 Trial in Advanced BCC

The EC approval was based on data from an ongoing open-label, multi-center, non-randomized Phase 2 trial of patients with unresectable locally advanced BCC or metastatic BCC (nodal or distant). Patients in both cohorts had either progressed on HHI therapy, had not had an objective response after nine months on HHI therapy, or were intolerant of prior HHI therapy. The primary efficacy endpoint was confirmed ORR, and a key secondary endpoint was DOR, assessed by independent central review.

About Libtayo

Libtayo is a fully human monoclonal antibody targeting the immune checkpoint receptor PD-1 on T-cells. By binding to PD-1, Libtayo has been shown to block cancer cells from using the PD-1 pathway to suppress T-cell activation.

The recommended dose of Libtayo is 350 mg administered as an intravenous infusion over 30 minutes every three weeks, until disease progression or unacceptable toxicity. Libtayo is available as a single-dose 350 mg vial. No PD-L1 or tumor mutational burden (TMB) testing is required before starting treatment with Libtayo for advanced BCC.

The extensive clinical program for Libtayo is focused on difficult-to-treat cancers. Current clinical development programs include Libtayo in combination with chemotherapy for advanced NSCLC irrespective of PD-L1 expression and Libtayo monotherapy for advanced cervical cancer. Libtayo is also being investigated in combination with either conventional or novel therapeutic approaches for other solid tumors and blood cancers. These potential uses are investigational, and their safety and efficacy have not been evaluated by any regulatory authority.

The generic name for Libtayo in its approved U.S. indications is cemiplimab-rwlc, with rwlc as the suffix designated in accordance with Nonproprietary Naming of Biological Products Guidance for Industry issued by the U.S. Food and Drug Administration (FDA). Libtayo is being jointly developed by Regeneron and Sanofi under a global collaboration agreement.

About Regeneron’s VelocImmune Technology

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

IMPORTANT SAFETY INFORMATION AND INDICATION FOR U.S. PATIENTS

What is Libtayo?

Libtayo is a prescription medicine used to treat people with a type of skin cancer called cutaneous squamous cell carcinoma (CSCC) that has spread or cannot be cured by surgery or radiation.

Libtayo is a prescription medicine used to treat people with a type of skin cancer called basal cell carcinoma that cannot be removed by surgery (locally advanced BCC) and have received treatment with an HHI, or cannot receive treatment with an HHI.

Libtayo is a prescription medicine used to treat people with a type of skin cancer called basal cell carcinoma that has spread (metastatic BCC) and have received treatment with a hedgehog pathway inhibitor (HHI), or cannot receive treatment with an HHI. This use is approved based on how many patients responded to treatment and how long they responded. Studies are ongoing to provide additional information about clinical benefit.

Libtayo is a prescription medicine used to treat people with a type of lung cancer called non-small cell lung cancer (NSCLC). Libtayo may be used as your first treatment when your lung cancer has not spread outside your chest (locally advanced lung cancer) and you cannot have surgery or chemotherapy with radiation, or your lung cancer has spread to other areas of your body (metastatic lung cancer), and your tumor tests positive for high "PD-L1" and your tumor does not have an abnormal "EGFR", "ALK "or "ROS1" gene.

It is not known if Libtayo is safe and effective in children.

What is the most important information I should know about Libtayo?

Libtayo is a medicine that may treat certain cancers by working with your immune system. Libtayo can cause your immune system to attack normal organs and tissues in any area of your body and can affect the way they work. These problems can sometimes become severe or life-threatening and can lead to death. You can have more than one of these problems at the same time. These problems may happen anytime during treatment or even after your treatment has ended.

Call or see your healthcare provider right away if you develop any new or worsening signs or symptoms, including:

Lung problems: cough, shortness of breath, or chest pain
Intestinal problems: diarrhea (loose stools) or more frequent bowel movements than usual, stools that are black, tarry, sticky or have blood or mucus, or severe stomach-area (abdomen) pain or tenderness
Liver problems: yellowing of your skin or the whites of your eyes, severe nausea or vomiting, pain on the right side of your stomach area (abdomen), dark urine (tea colored), or bleeding or bruising more easily than normal
Hormone gland problems: headache that will not go away or unusual headaches, eye sensitivity to light, eye problems, rapid heartbeat, increased sweating, extreme tiredness, weight gain or weight loss, feeling more hungry or thirsty than usual, urinating more often than usual, hair loss, feeling cold, constipation, your voice gets deeper, dizziness or fainting, or changes in mood or behavior, such as decreased sex drive, irritability, or forgetfulness
Kidney problems: decrease in your amount of urine, blood in your urine, swelling of your ankles, or loss of appetite
Skin problems: rash, itching, skin blistering or peeling, painful sores or ulcers in mouth or nose, throat, or genital area, fever or flu-like symptoms, or swollen lymph nodes
Problems can also happen in other organs and tissues. These are not all of the signs and symptoms of immune system problems that can happen with Libtayo. Call or see your healthcare provider right away for any new or worsening signs or symptoms, which may include: chest pain, irregular heartbeat, shortness of breath or swelling of ankles, confusion, sleepiness, memory problems, changes in mood or behavior, stiff neck, balance problems, tingling or numbness of the arms or legs, double vision, blurry vision, sensitivity to light, eye pain, changes in eyesight, persistent or severe muscle pain or weakness, muscle cramps, low red blood cells, or bruising
Infusion reactions that can sometimes be severe. Signs and symptoms of infusion reactions may include: nausea, chills or shaking, itching or rash, flushing, shortness of breath or wheezing, dizziness, feel like passing out, fever, back or neck pain, or facial swelling
Rejection of a transplanted organ. Your healthcare provider should tell you what signs and symptoms you should report and monitor you, depending on the type of organ transplant that you have had.
Complications, including graft-versus-host disease (GVHD), in people who have received a bone marrow (stem cell) transplant that uses donor stem cells (allogeneic). These complications can be serious and can lead to death. These complications may happen if you underwent transplantation either before or after being treated with Libtayo. Your healthcare provider will monitor you for these complications.
Getting medical treatment right away may help keep these problems from becoming more serious. Your healthcare provider will check you for these problems during your treatment with Libtayo. Your healthcare provider may treat you with corticosteroid or hormone replacement medicines. Your healthcare provider may also need to delay or completely stop treatment with Libtayo if you have severe side effects.

Before you receive Libtayo, tell your healthcare provider about all your medical conditions, including if you:

have immune system problems such as Crohn’s disease, ulcerative colitis, or lupus
have received an organ transplant
have received or plan to receive a stem cell transplant that uses donor stem cells (allogeneic)
have a condition that affects your nervous system, such as myasthenia gravis or Guillain-Barré syndrome
are pregnant or plan to become pregnant. Libtayo can harm your unborn baby
Females who are able to become pregnant:
Your healthcare provider will give you a pregnancy test before you start treatment.
You should use an effective method of birth control during your treatment and for at least 4 months after your last dose of Libtayo. Talk with your healthcare provider about birth control methods that you can use during this time.
Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with Libtayo.
are breastfeeding or plan to breastfeed. It is not known if Libtayo passes into your breast milk. Do not breastfeed during treatment and for at least 4 months after the last dose of Libtayo.
Tell your healthcare provider about all the medicines you take, including prescription and over- the-counter medicines, vitamins, and herbal supplements.

The most common side effects of Libtayo include muscle or bone pain, tiredness, rash, and diarrhea. These are not all the possible side effects of Libtayo. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. You may also report side effects to Regeneron Pharmaceuticals and Sanofi at 1-877-542-8296.

Please see full Prescribing Information, including Medication Guide.

On June 25, 2021 Sanofi and Regeneron reported that The European Commission (EC) has approved its PD-1 inhibitor Libtayo (cemiplimab) for the first-line treatment of adults with non-small cell lung cancer (NSCLC) whose tumor cells have ≥50% PD-L1 expression and no EGFR, ALK or ROS1 aberrations (Press release, Sanofi, JUN 25, 2021, View Source [SID1234584365]). Patients must have metastatic NSCLC or locally advanced NSCLC and not be a candidate for definitive chemoradiation.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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Libtayo is now approved for three advanced cancers in the European Union. The EC also approved Libtayo in advanced basal cell carcinoma, the first treatment to be indicated for those patients who have progressed on or are intolerant to a hedgehog pathway inhibitor (HHI). In 2019, Libtayo was approved by the EC as the first treatment for adults with metastatic or locally advanced cutaneous squamous cell carcinoma (CSCC) who are not candidates for curative surgery or curative radiation. Across all of its approved indications, Libtayo had a generally consistent safety profile. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue during or after treatment with Libtayo.

"We are confident that Libtayo has the potential to become an important treatment option for patients in the European Union and thank all the investigators, patients and their families who helped us reach this milestone," said Peter C. Adamson, M.D., Global Development Head, Oncology at Sanofi. "We are anticipating results from our ongoing Phase 3 trial of Libtayo plus chemotherapy in patients with advanced non-small cell lung cancer and remain committed to studying Libtayo in additional cancer settings where there is the potential to improve the outcome for patients."

The EC approval in advanced NSCLC is based on data from a global Phase 3 trial that enrolled 710 patients from 24 countries. The trial, which was one of the largest for a PD-1 inhibitor in advanced NSCLC, was designed to be more reflective of clinical practice by including challenging-to-treat and often underrepresented disease characteristics. Among those enrolled, 12% had pre-treated and clinically stable brain metastases, 44% had squamous cell histology and 16% had locally advanced NSCLC that was not a candidate for definitive chemoradiation. Furthermore, patients whose disease progressed in the trial were able to change their therapy: those assigned to chemotherapy could crossover to Libtayo treatment, while those assigned to Libtayo monotherapy could continue Libtayo treatment and add four cycles of chemotherapy.

In the overall study population, Libtayo significantly reduced the risk of death by 32% and extended median overall survival (OS) by 8 months compared to chemotherapy, even with 74% of patients crossing over to Libtayo following disease progression on chemotherapy (hazard ratio [HR]: 0.68; 95% confidence interval [CI]: 0.53-0.87; p=0.0022). The median OS was 22 months for Libtayo (range: 18 months to not evaluable) and 14 months for chemotherapy (range: 12 to 19 months). A prespecified analysis of data from patients whose cancers had PD-L1 expression ≥50% (n=563) based on a validated assay was also conducted. As published in The Lancet, Libtayo reduced the risk of death by 43% for patients in this population; median OS was not reached for Libtayo (95% CI: 18 months to not evaluable) and was 14 months for chemotherapy (95% CI: 11 to 18 months).

In the Phase 3 trial, safety was assessed in 697 patients, with a duration of exposure of 27 weeks (range: 9 days to 115 weeks) for the Libtayo group and 18 weeks (range: 18 days to 87 weeks) for the chemotherapy group. Serious adverse reactions (AEs) in at least 2% of patients were pneumonia (5% Libtayo, 6% chemotherapy) and pneumonitis (2% Libtayo, 0% chemotherapy). Treatment was permanently discontinued due to AEs in 6% of Libtayo patients; AEs resulting in permanent discontinuation in at least 2 patients were pneumonitis, pneumonia, ischemic stroke and increased aspartate aminotransferase. No new Libtayo safety signals were observed.

"Libtayo has demonstrated a highly significant improvement in overall survival compared to chemotherapy for patients with advanced non-small cell lung cancer with high PD-L1 expression and a variety of challenging-to-treat disease characteristics," said Israel Lowy, M.D., Ph.D., Senior Vice President, Translational and Clinical Sciences, Oncology at Regeneron. "Beyond the primary analysis, we continue to conduct post-hoc analyses of our Phase 3 trial with the goal of informing treatment in this patient population."

About the Phase 3 Trial in Advanced NSCLC

EMPOWER-Lung 1 was an open-label, randomized, multi-center Phase 3 trial designed to investigate Libtayo monotherapy compared to platinum-doublet chemotherapy as first-line treatment in patients with advanced NSCLC who tested positive for PD-L1 in ≥50% of tumor cells and had no EGFR, ALK or ROS1 aberrations. PD-L1 expression was confirmed using the Agilent Dako PD-L1 IHC 22C3 pharmDx kit.

The trial randomized 710 patients 1:1 who had either previously untreated metastatic NSCLC (stage IV) or locally advanced NSCLC (stage IIIB/C) who were not candidates for surgical resection or definitive chemoradiation or who had progressed after treatment with definitive chemoradiation. Those receiving Libtayo were intravenously administered 350 mg dose every three weeks for up to 108 weeks, while those receiving chemotherapy received an investigator-selected, platinum-doublet chemotherapy regimen for four to six cycles (with or without maintenance pemetrexed chemotherapy).

The primary endpoints were OS and progression-free survival, and secondary endpoints included objective response rate, duration of response and quality of life. In 2020, the trial was stopped early due to a significant improvement in OS.

About Libtayo

Libtayo is a fully human monoclonal antibody targeting the immune checkpoint receptor PD-1 on T-cells. By binding to PD-1, Libtayo has been shown to block cancer cells from using the PD-1 pathway to suppress T-cell activation.

The extensive clinical program for Libtayo is focused on difficult-to-treat cancers. Current clinical development programs include Libtayo in combination with chemotherapy for advanced NSCLC irrespective of PD-L1 expression and Libtayo monotherapy for advanced cervical cancer. Libtayo is also being investigated in combination with either conventional or novel therapeutic approaches for other solid tumors and blood cancers. These potential uses are investigational, and their safety and efficacy have not been evaluated by any regulatory authority.

The generic name for Libtayo in its approved U.S. indications is cemiplimab-rwlc, with rwlc as the suffix designated in accordance with Nonproprietary Naming of Biological Products Guidance for Industry issued by the U.S. Food and Drug Administration (FDA). Libtayo is being jointly developed by Regeneron and Sanofi under a global collaboration agreement.

On June 25, 2021 Sandoz reported the launch of generic oncology treatment Pemetrexed in 11 countries across Europe, including Germany, Switzerland, Netherlands, and Spain (Press release, Novartis, JUN 25, 2021, View Source [SID1234584364]).

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Pemetrexed, as a monotherapy or in combination with cisplatin, is indicated for first-line, second-line and maintenance treatment of patients with locally advanced or metastatic Non-Small Cell Lung Cancer (NSCLC) other than predominantly squamous cell histology, and for the treatment of chemotherapy naïve patients with unresectable malignant pleural mesothelioma.3

Globally, 1.8 million people died from lung cancer in 2020 including over 26,000 deaths from mesothelioma, and approximately 2.2 million new cases of lung cancer including 31,000 new cases of mesothelioma were diagnosed.4 NSCLC is the most prevalent form of the disease, affecting approximately 85% of those diagnosed with lung cancer.5,6

"At Sandoz, we are committed to using our expertise in product development to enable us to deliver high quality, innovative products that address the needs of patients and healthcare professionals," said Rebecca Guntern, Head of Sandoz Region Europe. "By providing Pemetrexed in a ready-to-dilute format and in an additional, higher-strength dosage, we believe that this treatment option will not only be more cost-effective for payers, but patients and physicians will also be able to benefit from the reduced preparation steps required."

Pemetrexed is a multi-targeted antifolate anti-cancer agent that disrupts crucial folate-dependent metabolic processes essential for cell replication. It inhibits folate-dependent enzymes critical to the de-novo biosynthesis of nucleotides leading to the disruption of DNA replication. Patients receive the treatment via a 10-minute intravenous infusion in a hospital setting.3

Further launches across Europe are expected throughout the second half of 2021.

On June 25, 2021 MorphoSys AG (FSE: MOR; NASDAQ: MOR) and Incyte (NASDAQ: INCY) reported that the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion recommending the conditional marketing authorization of tafasitamab in combination with lenalidomide, followed by tafasitamab monotherapy, for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are not eligible for autologous stem cell transplantation (ASCT) (Press release, MorphoSys, JUN 25, 2021, View Source [SID1234584363]).

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"The CHMP’s positive opinion of tafasitamab is a pivotal step towards addressing an urgent unmet medical need for the 30-40% of patients with relapsed or refractory DLBCL who do not respond to initial therapy or relapse thereafter," said Steven Stein, M.D., Chief Medical Officer, Incyte. "Following the U.S. FDA’s approval of tafasitamab in July 2020, we eagerly await the European Commission’s decision as we look forward to bringing this new therapy to eligible patients in Europe as soon as possible."

"Tafasitamab in combination with lenalidomide represents an important new targeted treatment option for patients with relapsed or refractory DLBCL," said Dr. Malte Peters, Chief Research & Development Officer, MorphoSys. "Patients with relapsed or refractory DLBCL have limited treatment options and often face a poor prognosis. There is an urgent need for effective therapies and if approved, this combination could provide patients in Europe with an important new therapeutic option."

The CHMP opinion to recommend the use of tafasitamab is now being reviewed by the European Commission, which has the authority to grant marketing authorization for medicinal products in the European Union (EU). If approved, tafasitamab would be commercialized in the EU under the brand name Minjuvi.

DLBCL is the most common type of non-Hodgkin lymphoma in adults worldwide comprising 40% of all cases1 and characterized by rapidly growing masses of malignant B-cells in the lymph nodes, spleen, liver, bone marrow or other organs.2 It is an aggressive disease with about one in three patients not responding to initial therapy or relapsing thereafter.3 In Europe, each year approximately 16,000 patients are diagnosed with relapsed or refractory DLBCL.4,5,6

MorphoSys and Incyte share global development rights to tafasitamab and Incyte has exclusive commercialization rights to tafasitamab outside the United States. MorphoSys and Incyte co-commercialize tafasitamab under the brand name Monjuvi in the United States.

About L-MIND

The L-MIND trial is a single arm, open-label Phase 2 study (NCT02399085) investigating the combination of tafasitamab and lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who have had at least one, but no more than three prior lines of therapy, including an anti-CD20 targeting therapy (e.g., rituximab), who are not eligible for high-dose chemotherapy (HCD) or autologous stem cell transplant (ASCT). The study’s primary endpoint is overall response rate (ORR). Secondary outcome measures include duration of response (DoR), progression-free survival (PFS) and overall survival (OS). The study reached its primary completion in May 2019.

For more information about L-MIND, visit View Source

About Tafasitamab

Tafasitamab is a humanized Fc-modified cytolytic CD19 targeting monoclonal antibody. In 2010, MorphoSys licensed exclusive worldwide rights to develop and commercialize tafasitamab from Xencor, Inc. Tafasitamab incorporates an XmAb engineered Fc domain, which mediates B-cell lysis through apoptosis and immune effector mechanism including Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) and Antibody-Dependent Cellular Phagocytosis (ADCP).

Monjuvi (tafasitamab-cxix) is approved by the U.S. Food and Drug Administration in combination with lenalidomide for the treatment of adult patients with relapsed or refractory DLBCL not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not eligible for autologous stem cell transplant (ASCT). 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 a confirmatory trial(s).

Tafasitamab is being clinically investigated as a therapeutic option in B-cell malignancies in several ongoing combination trials.

Minjuvi and Monjuvi are registered trademarks of MorphoSys AG. Tafasitamab is marketed under the brand name Monjuvi in the US. If approved in the EU, tafasitamab will be marketed under the brand name Minjuvi.

XmAb is a registered trademark of Xencor, Inc.