Policy & Regulation
Bristol Myers Squibb, bluebird bio Submit Biologics License Application to FDA for Idecabtagene Vicleucel (Ide-cel, bb2121) for Adults with Relapsed and Refractory Multiple Myeloma
31 July 2020 - - US-based biopharmaceutical company Bristol Myers Squibb (NYSE: BMY) and US-based gene therapy specialist bluebird bio, Inc. (NASDAQ: BLUE) have submitted a Biologics License Application to the US Food and Drug Administration for idecabtagene vicleucel (ide-cel; bb2121), the companies' investigational B-cell maturation antigen -directed chimeric antigen receptor T cell immunotherapy, for the treatment of adult patients with relapsed and refractory multiple myeloma, the companies said.

This submission provides further details on the Chemistry, Manufacturing and Controls module to address the outstanding regulatory requests from the FDA in May 2020 following the original BLA submission from March 2020.

The submission is based on results from the pivotal Phase 2 KarMMa study evaluating the efficacy and safety of ide-cel in relapsed and refractory multiple myeloma patients exposed to an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody.

Results from the study were shared during an oral presentation as part of the American Society of Clinical Oncology 2020 (ASCO20) Virtual Scientific Program.

Multiple myeloma is a cancer of plasma cells. The cause of multiple myeloma is not known and currently there is no cure; however, there are a number of treatment options available that can lead to response.

Patients who have already been treated with some available therapies but continue to have progression of their disease have "relapsed" and "refractory" multiple myeloma, meaning their cancer has returned after they have received initial treatments.

Patients with relapsed and refractory multiple myeloma that have been exposed to all three major drug classes, including an IMiD agent, a PI and an anti-CD38 antibody, have fewer treatment options and poor outcomes, including shorter response durations and lower overall survival.

Ide-cel was granted Breakthrough Therapy Designation by the FDA, and PRIority MEdicines (PRIME) designation and validation of its Marketing Authorization Application by the European Medicines Agency for relapsed and refractory multiple myeloma.

Ide-cel is not approved for any indication in any geography.

US FDA approval of ide-cel by March 31, 2021 is one of the required remaining milestones of the Contingent Value Rights issued upon the close of the Celgene acquisition in 4Q19. The other is US FDA approval of liso-cel by December 31, 2020.

The company is committed to working with FDA to progress both applications and achieve the remaining regulatory milestones required by the CVR.

Ide-cel is a B-cell maturation antigen -directed genetically modified autologous chimeric antigen receptor T cell immunotherapy.

The ide-cel CAR is comprised of a murine extracellular single-chain variable fragment specific for recognising BCMA, attached to a human CD8 α hinge and transmembrane domain fused to the T cell cytoplasmic signaling domains of CD137 4-1BB and CD3-ζ chain, in tandem.

Ide-cel 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.

Ide-cel is being developed as part of a Co-Development, Co-Promotion and Profit Share Agreement between Bristol Myers Squibb and bluebird bio. Ide-cel was granted accelerated assessment by the European Medicines Agency on March 26, 2020, and the MAA was validated by the EMA on May 20, 2020.

KarMMa (NCT03361748) is a pivotal, open-label, single-arm, multicenter, multinational, Phase 2 study evaluating the efficacy and safety of ide-cel in adults with relapsed and refractory multiple myeloma in North America and Europe.

The primary endpoint of the study is overall response rate as assessed by an independent review committee according to the International Myeloma Working Group criteria.

Complete response rate is a key secondary endpoint. Other efficacy endpoints include time to response, duration of response, progression-free survival, overall survival, minimal residual disease evaluated by Next-Generation Sequencing assay and safety.

The study enrolled 140 patients, of whom 128 received ide-cel across the target dose levels of 150-450 x 106 CAR+ T cells after receiving lymphodepleting chemotherapy.

All enrolled patients had received at least three prior treatment regimens, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody, and were refractory to their last regimen, defined as progression during or within 60 days of their last therapy.


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