Bristol Myers Squibb’s Abecma (idecabtagene vicleucel) Becomes First CAR T Cell Therapy Approved in the European Union in Earlier Lines for Triple-Class Exposed Relapsed and Refractory Multiple Myeloma
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Insights
The European Commission's approval of Abecma for relapsed and refractory multiple myeloma offers a significant advancement in the treatment landscape. This is the first chimeric antigen receptor (CAR) T cell therapy available for use in earlier lines of treatment for this patient population in the EU. The clinical data showing a 51% reduction in risk of disease progression or death is a substantial improvement over the current standard regimens. From a medical perspective, this approval could potentially lead to a paradigm shift in how multiple myeloma is managed after first-line therapies fail.
Abecma's safety profile, with mostly low-grade and transient occurrences of cytokine release syndrome and neurotoxicity, suggests that the therapy is generally well-tolerated, which is important for patient quality of life. However, it's important to note that while the median overall survival (OS) data appears promising, the crossover design of the KarMMa-3 trial may have confounded these results. Thus, further studies and real-world evidence are needed to fully understand the long-term benefits and potential risks associated with Abecma.
The approval of Abecma by the European Commission is not only a milestone for Bristol Myers Squibb but also represents a notable development in the biotechnology sector. The data from the KarMMa-3 clinical trial underscores the effectiveness of personalized cell therapies in treating complex hematologic cancers. The observed progression-free survival (PFS) of 13.8 months compared to 4.4 months with standard regimens indicates a meaningful clinical benefit.
From a research standpoint, the success of this therapy could encourage further investment in CAR T-cell therapies and other forms of personalized medicine. The manufacturing success rate of over 90% reported by Bristol Myers Squibb suggests that the company has addressed some of the initial challenges associated with the production of these complex therapies, which could have positive implications for the scalability and accessibility of Abecma across the EU.
The approval of Abecma in the European Union is likely to have a positive impact on Bristol Myers Squibb's market position in the oncology segment. As the first CAR T cell therapy approved for earlier lines of treatment for multiple myeloma in the EU, Abecma could potentially capture a significant market share from existing therapies. The company's focus on increasing manufacturing capacity and successful global manufacturing rate are indicators of its commitment to meet demand and may positively influence investor sentiment.
Moreover, the completion of reimbursement procedures will be a critical factor in determining the commercial success of Abecma in the EU. The adoption rate by healthcare providers and the therapy's inclusion in treatment guidelines will also play a role in its market penetration. Investors should monitor the post-approval real-world efficacy and safety data, as this will influence long-term adoption and the potential for expansion into additional markets.
Abecma demonstrated superiority over standard regimens in the Phase 3 KarMMa-3 trial, with a
Approval reinforces Bristol Myers Squibb’s commitment to bring the transformative potential of cell therapy into earlier lines of treatment
“Today’s approval in the European Union marks an exciting milestone in our efforts to bring the transformative potential of cell therapies into earlier lines of treatment,” said Monica Shaw, M.D., senior vice president and head of European Markets, Bristol Myers Squibb. “Abecma is an important treatment option for patients with triple-class exposed relapsed and refractory multiple myeloma who have received at least two prior therapies and is leading the way toward a promising shift in the treatment paradigm.”
The current treatment paradigm for multiple myeloma includes IMiDs, PIs, and anti-CD38 monoclonal antibodies; however, many patients go on to relapse and/or become refractory to these classes of therapy. With increased use of the three main classes of therapy as combination regimens, more patients are becoming triple-class exposed earlier in their treatment journey. There have historically been limited options for patients with triple-class exposed relapsed and/or refractory multiple myeloma, and patients tend to have poor outcomes with a median progression-free survival of three to five months.
“As patients with multiple myeloma become exposed to the three main classes of therapy earlier in treatment and still experience relapsed and/or refractory disease, it is critical that we continue to add innovative treatment options to our arsenal that can potentially provide long-term disease control,” said Paula Rodriguez-Otero, M.D., Ph.D., Department of Hematology, Clinica Universidad de
With a significant increase in manufacturing capacity and over
Based on the KarMMa-3 study, Abecma is also the first cell therapy approved in
Abecma is also approved in the
*Centralized Marketing Authorization does not include approval in
Abecma KarMMa-3 Clinical Trial Results
The EC approval of Abecma is based on results from KarMMa-3, a pivotal Phase 3, open-label, global, randomized controlled study evaluating Abecma compared to standard combination regimens in patients with relapsed and refractory multiple myeloma who received two to four prior lines of treatment, including an IMiD, a PI, and an anti-CD38 monoclonal antibody (triple-class exposed), and who were refractory to the last treatment regimen.
At a pre-specified interim analysis with a median follow-up of 18.6 months, treatment with Abecma (n=254) significantly improved progression-free survival (PFS), the study’s primary endpoint, compared to standard regimens (n=132), with a median PFS of 13.8 months (
The KarMMa-3 trial had a patient-centric design that allowed for crossover from standard regimens to Abecma upon confirmed disease progression, with more than half (
Based on a pooled analysis of the KarMMa, CRB-401 and KarMMa-3 studies (n=409), Abecma has exhibited a well-established and consistent safety profile with mostly low-grade and transient occurrences of cytokine release syndrome (CRS) and neurotoxicity. In patients treated with Abecma, any grade CRS has occurred in
About Abecma
Abecma is a CAR T cell therapy that recognizes and binds to the B-cell maturation antigen (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 the first-in-class BCMA-directed CAR T cell immunotherapy approved by the
Abecma is being jointly developed and commercialized in the
Full European Summary of Product Characteristics for Abecma is available from the EMA website at www.ema.europa.eu.
Abecma
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.
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.
WARNINGS AND PRECAUTIONS:
Cytokine Release Syndrome (CRS): CRS, including fatal or life-threatening reactions, occurred following treatment with ABECMA in
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. 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 (single dose:
Monitor patients at least daily for 7 days following ABECMA infusion at the REMS-certified healthcare facility for signs or symptoms of CRS and monitor patients for signs or symptoms of CRS for at least 4 weeks after ABECMA 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, including immune effector cell-associated neurotoxicity syndrome (ICANS), which may be severe or life- threatening, occurred concurrently with CRS, after CRS resolution, or in the absence of CRS following treatment with ABECMA. Neurologic toxicities occurred in
Monitor patients at least daily for 7 days following ABECMA infusion at the REMS-certified healthcare facility for signs or symptoms of neurologic toxicities and monitor patients for signs or symptoms of neurologic toxicities for at least 4 weeks after ABECMA infusion and treat promptly. Rule out other causes of neurologic symptoms. Neurologic toxicity should be managed with supportive care and/or corticosteroids as needed.
Counsel patients to seek immediate medical attention should signs or symptoms occur at any time.
Hemophagocytic Lymphohistiocytosis (HLH)/Macrophage Activation Syndrome (MAS): HLH/MAS occurred in
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
Febrile neutropenia was observed in
Viral Reactivation: 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: In the clinical study,
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.
Hypogammaglobulinemia: Hypogammaglobulinemia was reported as an adverse event in
Monitor immunoglobulin levels after treatment with ABECMA and administer IVIG for IgG <400 mg/dl. Manage appropriately per local institutional guidelines, including infection precautions and antibiotic or antiviral prophylaxis.
The safety of immunization with live viral vaccines during or after 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, 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 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.
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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 understanding of causal human biology, cutting-edge capabilities and differentiated research platforms uniquely position the company to approach 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. 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
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