Abecma tripled progression-free survival compared to standard regimens in the Phase 3 KarMMa-3 trial, with a 51% reduction in risk of disease progression or death and a well-established safety profile

Expanded approval brings this personalized CAR T cell therapy to more patients with relapsed or refractory multiple myeloma earlier in their treatment journey as a one-time infusion offering meaningful treatment-free intervals when responding to therapy

Abecma is now approved in the U.S., Japan, Switzerland and the EU for earlier use for triple-class exposed relapsed and/or refractory multiple myeloma, underscoring BMS’ commitment to delivering Abecma globally, with consistently high manufacturing success rates and continuous increases in capacity

PRINCETON, NJ, & CAMBRIDGE, MA, USA I April 05, 2024 I Bristol Myers Squibb (NYSE: BMY) and 2seventy bio, Inc. (Nasdaq: TSVT) have announced that on April 4, 2024, the U.S. Food and Drug Administration (FDA) approved Abecma® (idecabtagene vicleucel; ide-cel) for the treatment of adult patients with relapsed or refractory multiple myeloma after two or more prior lines of therapy including an immunomodulatory agent (IMiD), a proteasome inhibitor (PI), and an anti-CD38 monoclonal antibody, based on results from the KarMMa-3 trial.This approval expands Abecma’s indication, making it available in earlier lines to patients who have relapsed or become refractory after exposure to these three main classes of treatment (triple-class exposed), after two prior lines of therapy. Abecma is administered as a one-time infusion, with a new recommended dose range of 300 to 510 x 106 CAR-positive T cells. Please see the Important Safety Information section below, including Boxed WARNINGS for Abecma regarding Cytokine Release Syndrome, Neurologic Toxicities, Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome, Prolonged Cytopenia, and Secondary Hematological Malignancies.

Abecma has demonstrated a progression-free survival benefit three times that of standard regimens in relapsed or refractory multiple myeloma, and we are now bringing the promise of cell therapy to patients earlier in their treatment journey,” said Bryan Campbell, senior vice president, Head of Commercial, Cell Therapy, Bristol Myers Squibb. “This approval underpins our commitment to addressing the unmet needs of more patients living with multiple myeloma by improving upon the current treatment paradigm, and we remain steadfast in our pursuit of innovation and advancing cell therapy research to deliver potentially transformative therapies.”

“We are extremely pleased that Abecma will be available to many more patients in the U.S.,” said Chip Baird, chief executive officer, 2seventy bio. “This approval represents another important milestone for patients, for Abecma, and for 2seventy bio as we remain committed to increasing treatment options and working to improve outcomes for patients living with multiple myeloma.”

Despite advances in treatment, multiple myeloma remains an incurable disease characterized by periods of remission and relapse. In early lines of treatment, regimens consisting of combinations of IMiDs, PIs, and anti-CD38 monoclonal antibodies are often used to help manage the disease. Unfortunately, as many patients go on to relapse and/or become refractory to these classes of therapy, more patients are becoming triple-class exposed earlier in their treatment journey. There are limited options for these patients, and triple-class exposed relapsed and/or refractory multiple myeloma is associated with poor outcomes and a median progression-free survival (PFS) of three to five months. In this patient population with high unmet need, Abecma has demonstrated clinically meaningful and statistically significant improvements in PFS (95% CI: 13.3 months vs. 4.4 months [HR: 0.49; p<0.0001]). In addition, Abecma exhibited a well-established safety profile with mostly low-grade cytokine release syndrome and neurotoxicity. No cases of Parkinsonism were reported in the study.

“The results of the KarMMa-3 study are remarkable, especially given the historic outcomes with standard regimens for these patients with relapsed or refractory disease,” said Al-Ola A. Abdallah, M.D., University of Kansas, Clinical Associate Professor, Clinical Director, Hematologic Malignancies and Cellular Therapeutics and chair of U.S. Myeloma Innovations Research Collaborative. “With this approval, these patients now have an opportunity to be treated at an earlier line of therapy with a potentially transformative therapy that offers significantly improved progression-free survival for this difficult-to-treat disease that has had no established treatment approach.”

To support this approval and future expansions, Bristol Myers Squibb has made continuous investments to increase manufacturing capacity and has shown a consistently high manufacturing success rate of 94% for Abecma in the commercial setting.

Abecma was recently approved in Japan, Switzerland and the European Union for adult patients with triple-class exposed relapsed and/or refractory multiple myeloma after two prior lines of therapy, making it the only CAR T cell therapy available globally for earlier lines of therapy for patients with triple-class exposed relapsed and/or refractory multiple myeloma. Abecma is also currently 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.

KarMMa-3 Pivotal Trial Results

The KarMMa-3 trial is a pivotal, Phase 3, open-label, global, randomized, controlled trial evaluating Abecma compared to standard regimens in patients with relapsed and refractory multiple myeloma who have received two to four prior lines of treatment, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody, and were refractory to the last treatment regimen, with 94% of patients with disease refractory to prior treatment with daratumumab. KarMMa-3 is the only Phase 3 trial to evaluate a CAR T cell therapy in a patient population consisting entirely of triple-class exposed relapsed and refractory multiple myeloma patients. The trial’s patient-centric design allowed for crossover from standard regimens to Abecma upon confirmed disease progression. At the time of the final progression-free survival (PFS) analysis, more than half (56%) of patients in the standard regimens arm crossed over to receive Abecma as a subsequent therapy.

In the study, 254 patients were randomized to receive Abecma and 132 were randomized to receive standard regimens that consisted of combinations that included daratumumab, pomalidomide, and dexamethasone (DPd), daratumumab, bortezomib, and dexamethasone (DVd), ixazomib, lenalidomide, and dexamethasone (IRd), carfilzomib and dexamethasone (Kd) or elotuzumab, pomalidomide and dexamethasone (EPd) chosen based on their most recent treatment regimen and investigator discretion. In the Abecma arm, pretreatment consisted of leukapheresis and optional bridging therapy. The choice to use bridging therapy was at the discretion of the investigator.

At an estimated median duration of follow-up of 15.9 months at the primary PFS analysis, Abecma more than tripled the primary endpoint of PFS compared with standard regimens, with a median PFS of 13.3 months (95% CI: 11.8-16.1) vs. 4.4 months (95% CI: 3.4-5.9), respectively (HR:0.49; 95% CI: 0.38-0.64; p<0.0001), representing a 51% reduction in the risk of disease progression or death with Abecma. Abecma also showed a significant improvement in overall response rates (p<0.0001) with the majority (71%) of patients treated with Abecma achieving a response, and 39% achieving a complete or stringent complete response. In comparison, less than half of patients (42%) who received standard regimens achieved a response, with 5% experiencing a complete response or stringent complete response. Responses were durable with Abecma, with a median duration of response of 14.8 months (95% CI: 12.0-18.6). In those patients who derived a complete response or better, median duration of response was 20 months (95% CI: 15.8-24.3).

Abecma has exhibited a well-established and consistent safety profile with mostly low-grade cytokine release syndrome (CRS) and neurotoxicity. Among patients who received Abecma in the KarMMa and KarMMa-3 studies (n=349), any grade CRS occurred in 89% of patients, including Grade >3 CRS in 7% of patients, and three cases (0.9%) of Grade 5 CRS reported. The median time to onset of CRS was 1 day (range: 1-27 days), and the median duration of CRS was 5 days (range: 1-63 days). Any grade neurotoxicity occurred in 40% of patients treated with Abecma in the KarMMa and KarMMa-3 studies, including Grade 3 neurotoxicity in 4% of patients, and two cases (0.6%) of Grade 4 neurotoxicity reported. At the safety update for KarMMa-3, one case of Grade 5 neurotoxicity was reported. The median time to onset of neurotoxicity was 2 days (range: 1-148 days), and the median duration of neurotoxicity was 8 days (range: 1-720 days).

About Abecma

Abecma is a CAR T cell therapy that 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 between Bristol Myers Squibb and 2seventy bio.

This approval further underscores Bristol Myers Squibb’s deep knowledge and experience in cell therapy science and continued clinical advancements for multiple myeloma patients. The companies’ broad clinical development program for Abecma includes ongoing and planned clinical studies (KarMMa-2, KarMMa-3, KarMMa-9) for patients with multiple myeloma. For more information visit clinicaltrials.gov.

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 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.

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

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.

About 2seventy bio

Our name, 2seventy bio, reflects why we do what we do – TIME. Cancer rips time away, and our goal is to work at the maximum speed of translating human thought into action – 270 miles per hour – to give the people we serve more time. We are building the leading immuno-oncology cell therapy company, focused on discovering and developing new therapies that truly disrupt the cancer treatment landscape. With a deep understanding of the human body’s immune response to tumor cells and how to translate cell therapies into practice, we’re applying this knowledge to deliver next generation cellular therapies that focus on a broad range of hematologic malignancies, including the first FDA-approved CAR T cell therapy for multiple myeloma, as well as solid tumors. Our research and development are focused on delivering therapies that are designed with the goal to “think” smarter and faster than the disease. Importantly, we remain focused on accomplishing these goals by staying genuine and authentic to our “why” and keeping our people and culture top of mind every day.

For more information, visit www.2seventybio.com.

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SOURCE: Bristol Myers Squibb