BMS, bluebird’s Multiple Myeloma Drug Becomes First BCMA Targeting CAR-T Therapy to Snag FDA Okay

FDA Approval

In August 2020, GSK’s antibody-drug conjugate, Blenrep, became the first FDA-approved anti-BCMA therapy for highly refractory Multiple Myeloma (MM). The agency has now granted authorization for a second drug targeting this antigen.

The B-cell maturation antigen (BCMA) has emerged as a highly sought-after antigen among MM researchers. Its highly selective expression in malignant plasma cells offers an ideal target for therapeutics to attack the cancer cells specifically and spare the healthy ones. Currently, a number of BCMA targeting therapeutics are in clinical development. This includes modalities like chimeric antigen receptor (CAR)-T cells, bispecific T cell engagers (BiTE), and antibody-drug conjugates (ADC).

 

New CAR-T on the Block

On March 26th, BMS and bluebird bio’s Abecma (ide-cel) became the first FDA-approved BCMA targeting CAR-T therapy for adult patients with refractory MM. It is also the fifth CAR T therapy overall to be approved by the FDA.

Multiple myeloma is a rare disease but is still the second most common blood cancer in the US. It often relapses even after advanced treatments. Patients who have undergone treatment with three major drug classes (triple-class exposed) involving an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody demonstrate poor response rates and gradually lose their chances of survival with every successive treatment.

Abecma is indicated for treating adult patients with relapsed or refractory MM who have undergone four or more prior lines of therapy, including the aforementioned three drug classes.

“CAR T cell therapies have shown transformational potential for the treatment of hematologic malignancies, and we, with our partners at bluebird bio, are proud to bring the first CAR T cell therapy to appropriate triple-class exposed patients with relapsed or refractory multiple myeloma, offering the chance for durable response,” said Samit Hirawat, M.D., Chief Medical Officer, Bristol Myers Squibb.

 

KarMMa Trial

The FDA approval is an outcome of positive data from the Phase 2 KarMMa trial that tested Abecma in a total of 127 patients with relapsed or refractory MM who have undergone prior treatments.

The study results determined from 100 patients showed that Abecma met the primary endpoint with an overall response rate (ORR) of 72%. For the secondary endpoints, the median time to respond to treatment was 30 days, and the median duration of response was 11 months. Besides, 28% of patients achieved a stringent complete response with a median duration of 19 months. Among the 28 patients, 65% of them had remission lasting at least 12 months.

BMS has been enjoying back-to-back regulatory successes for its cell therapies. Last month, the FDA greenlighted Breyanzi, an asset picked up from its $74 billion buyout of Celgene. The CD19 targeting CAR-T was approved for treating relapsed or refractory large B-Cell lymphoma.

“Bristol Myers Squibb is now the only company with two approved CAR T cell therapies with distinct targets of CD19 and BCMA. As our second FDA-approved CAR T cell therapy, Abecma underscores our commitment to deliver on the promise of cell therapies for patients who are battling aggressive and advanced blood cancers with limited effective treatment options.” Hirawat added.

 

Market Competition

Although Abecma is the first CAR-T approved for this indication, J&J and Legend Biotech’s cilta-cel is lurking closely. Cilta-cel, which is also a BCMA targeting CAR-T for refractory MM, has impressed everyone with its performance in a Phase 2 trial involving 97 patients.

The CARTITUDE-1 trial results presented at last year’s ASH meeting show that cilta-cel demonstrated an outstanding ORR of 97%. Also, 67% of them attained a deep complete response (no detectable cancer). The companies have already submitted a rolling submission of the BLA with the FDA, and the drug is also on its path to accelerated approval in Europe.

Additionally, several anti-BCMA CAR-T candidates are in different stages of clinical trials and have bagged special statuses from the FDA. They include CARsgen Therapeutics’ CT053, Cartesian Therapeutics’ Descartes-08, Precision BioSciences’ PBCAR269A, Poseida Therapeutics’ P-BCMA-101, to name a few.

BMS also has several investigational candidates in its own pipeline, namely bb21217, JCARH125, and FCARH143. With the entry of Blenrep and Abecma, the MM market is beginning to get crowded with anti-BCMA therapeutics.

Related Article: BMS’s Combo Therapy Involving LAG-3 Drug Impresses in Melanoma Trial

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