Bristol Myers Squibb and bluebird bio Resubmit BLA for BCMA-Targeted CAR-T Therapy Idecabtagene Vicleucel in Relapsed/Refractory Multiple Myeloma

Today, Bristol-Myers Squibb (BMS) and bluebird bio jointly announced that they have submitted a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for idecabtagene vicleucel (ide-cel, also known as bb2121), a CAR-T therapy co-developed by the two companies. This is a chimeric antigen receptor (CAR) T-cell immunotherapy targeting B-cell maturation antigen (BCMA) for the treatment of adult patients with relapsed/refractory multiple myeloma (R/R MM). The submission provides additional details in the Chemistry, Manufacturing, and Controls (CMC) module to address unmet regulatory requirements raised by the FDA in May 2020 following the initial BLA submission in March 2020.

Multiple myeloma (MM) is a malignant plasma cell disorder characterized by abnormal proliferation of plasma cells in the bone marrow and excessive production of monoclonal immunoglobulins. These abnormal plasma cells accumulate in the bone marrow and can form tumors in multiple bone sites throughout the body. Not only are these cells unable to perform normal functions, but the antibodies they produce also impair the bone marrow’s ability to generate healthy blood cells. Additionally, patients often present with multiple osteolytic lesions, hypercalcemia, anemia, and renal impairment. Although various therapies are currently available for multiple myeloma, many patients still develop resistance to all approved treatments, underscoring the critical importance of developing innovative therapeutic approaches for this disease.

B-cell maturation antigen (BCMA) is a protein widely expressed on the cancer cells of multiple myeloma, making it an important potential target for this aggressive blood cancer. Ide-cel can recognize and bind to BCMA on the surface of multiple myeloma cells, thereby leading to the proliferation and differentiation of CAR-T cells, followed by the killing of cells expressing BCMA. Previously, ide-cel has been granted Breakthrough Therapy designation by the FDA and received PRIME designation from the European Medicines Agency.

▲Key Efficacy Data for Ide-cel (Image Source: Reference [2])

This marketing application submission is based on the positive results from KarMMa, a pivotal single-arm, open-label Phase 2 clinical trial. Patients with relapsed/refractory multiple myeloma (R/R MM) enrolled in this trial had previously received at least an immunomodulatory drug (IMiD), a proteasome inhibitor (PI), and an anti-CD38 antibody, and had developed resistance to these therapies. Notably, 94% of patients were refractory to anti-CD38 antibody therapy, and 84% exhibited triple-class refractoriness. The trial results demonstrated that among the 128 efficacy-evaluable patients, the overall response rate (ORR) was 73.4%, and the complete response (CR) rate was 31.3%. With a median follow-up duration of 11.3 months, the progression-free survival (PFS) for these patients was 8.6 months.

The two companies stated that they are committed to working with the FDA to expedite the regulatory review process for ide-cel. We look forward to a smooth application process, bringing innovative treatment options to patients with multiple myeloma (MM) as soon as possible.

References:

[1] Bristol Myers Squibb and bluebird bio Announce Submission of Biologics License Application (BLA) to FDA for Idecabtagene Vicleucel (Ide-cel, bb2121) for Adults with Relapsed and Refractory Multiple Myeloma. Retrieved July 29, 2020, from https://www.businesswire.com/news/home/20200729005776/en

[2] Bristol-Myers Squibb and bluebird bio Announce Positive Top-line Results from the Pivotal Phase 2 KarMMa Study of Ide-cel in Relapsed and Refractory Multiple Myeloma. Retrieved March 31, 2020, from https://www.businesswire.com/news/home/20191206005463/en/Bristol-Myers-Squibb-bluebird-bio-Announce-Positive-Top-line

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