Bristol Myers Squibb Abecma approved in European Union for triple-class exposed relapsed and refractory multiple myeloma

“The 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 Navarra, Pamplona, Spain. “This expanded approval of ide-cel represents key progress in bringing a personalized therapy that delivers significantly improved, durable outcomes to patients with triple-class exposed relapsed and refractory multiple myeloma after two prior therapies.”

With a significant increase in manufacturing capacity and over 90% manufacturing success rate globally, Bristol Myers Squibb is prepared to meet increased demand for Abecma. The company is focused on making Abecma available in the EU for this indication, including completion of reimbursement procedures.

Based on the KarMMa-3 study, Abecma is also the first cell therapy approved in Switzerland for the treatment of adult patients with relapsed and refractory multiple myeloma who have received at least two prior lines of therapies and the first cell therapy approved in Japan for adult patients with triple-class exposed relapsed or refractory multiple myeloma after two prior lines of therapy.

Abecma is also approved in the U.S. for adult patients with triple-class exposed relapsed or refractory multiple myeloma after four or more prior lines of therapy and approved in Great Britain and Israel for adult patients with triple-class exposed relapsed and refractory multiple myeloma after three or more prior lines of therapy. A supplemental Biologics License Application for Abecma for triple-class exposed relapsed and refractory multiple myeloma is currently under review with the U.S. Food and Drug Administration (FDA). The FDA’s Oncologic Drugs Advisory Committee (ODAC) recently voted positively that Abecma demonstrated a favorable benefit/risk profile for patients with triple-class exposed relapsed or refractory multiple myeloma based on results from the pivotal Phase 3 KarMMa-3 study.

*Centralized Marketing Authorization does not include approval in Great Britain (England, Scotland and Wales).

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 (95% CI: 11.8-16.1) versus 4.4 months (95% CI: 3.4-5.8) (HR: 0.49 [95% CI: 0.38-0.63]; p<0.0001), representing a 51% reduction in the risk of disease progression or death. Results from the primary analysis, with a median follow-up of 30.9 months, were consistent with the interim analysis and represent the longest follow-up for a randomized Phase 3 CAR T cell therapy in this patient population. Treatment with Abecma also showed a significant improvement in overall response rate (ORR) with the majority (71.3% [95% CI: 65.7-76.8]) of patients treated with Abecma achieving a response, and 43.7% achieving a complete or stringent complete response. In comparison, less than half of patients (42.4% [95% CI: 34-50.9]) who received standard regimens achieved a response, with 5.3% experiencing a complete response or stringent complete response.

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 (56%) of patients in the standard regimens arm crossing over to receive Abecma as a subsequent therapy, due to disease progression while receiving standard regimens. Median overall survival (OS), a secondary endpoint of the study, was 41.4 months with Abecma (95% CI: 30.9-NR) and 37.9 months with standard regimens (95% CI: 23.4-NR) (95% CI: 0.73-1.40; HR: 1.01). Based on real-world evidence, median OS for patients with triple-class exposed relapsed and refractory multiple myeloma is approximately 13 months, underscoring the confounding impact that crossover had on the median OS observed with standard regimens in the KarMMa-3 trial.

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 84.6% of patients, with Grade ≥3 CRS occurring in 5.1% of patients and fatal (Grade 5) CRS reported in 0.7% of patients. The median time to onset of CRS was one day (range: 1 to 17) and the median duration of CRS was four days (range: 1 to 63). In the KarMMa and KarMMa-3 studies (n=353), any-grade neurotoxicity occurred in 16.1% of patients, with Grade 3/4 neurotoxicity occurring in 3.1% of patients, and no Grade 5 events reported. Median time to onset of neurotoxicity was three days (range: 1-317 days) and median duration of neurotoxicity was three days (range: 1-252 days). No cases of Parkinsonism were reported.

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 U.S. FDA 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 is being jointly developed and commercialized in the U.S. as part of a Co-Development, Co-Promotion, and Profit Share Agreement between Bristol Myers Squibb and 2seventy bio. Bristol Myers Squibb assumes sole responsibility for Abecma drug product manufacturing and commercialization outside of the U.S. The companies’ broad clinical development program for Abecma includes ongoing and planned clinical studies (KarMMa-2, KarMMa-9) for patients with multiple myeloma. 

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