BMS, bluebird Publish Ide-Cel Data in NEJM, One Month Ahead of PDUFA Date

Multiple Myeloma_Compressed

One month ahead of an expected review of ide-cel, a CAR-T treatment for multiple myeloma, data from a Phase II study published in a peer-reviewed journal shows the experimental drug hit its primary and secondary endpoint.

This morning, Bristol Myers Squibb and bluebird bio said data from the Phase II KarMMa study evaluating the safety and efficacy of ide-cel (idecabtagene vicleucel) met the primary endpoint of overall survival and the key secondary endpoint of complete response rate.

Data from the study, which was published in the New England Journal of Medicine (NEJM), demonstrates deep and durable responses with ide-cel treatment in patients with relapsed and refractory multiple myeloma (RRMM) who have received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody.

Clinically meaningful responses were reported in heavily pre-treated patients across all dose levels and in multiple high-risk subgroups, including those with high-risk cytogenetics, triple- or penta-refractory disease, high tumor burden at baseline, and extramedullary disease. Clinically meaningful improvement was also observed across measures for median duration of response, median progression-free survival and overall survival in treated patients.

Ide-cel demonstrated a safety profile consistent with known toxicities of CAR T cell therapies, regardless of dose level. The most frequently reported adverse events were cytopenia and cytokine release syndrome.

Ide-cel is an investigational B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T cell immunotherapy. In September 2020, the U.S. Food and Drug Administration accepted the companies’ Biologics License Application under priority review. The FDA is expected to make a decision on the CAR-T treatment by March 27. The research in the NEJM article were first presented at the virtual American Society of Clinical Oncology in 2020.

David Davidson, bluebird’s chief medical officer, said the KarMMa trial is the first pivotal study of a CAR T cell therapy in multiple myeloma. The publication of the data in the NEJM underscores the importance of the data and the outcomes observed in the patient population following a single-infusion of ide-cel. If approved, ide-cel could be a first-in-class BCMA-directed CAR T therapy for these patients.

The road to potential approval for ide-cel has been tough. In March 2020, the FDA declined to review the KarMMa data and issued a Refusal to File letter. The regulatory agency said it needed additional data in order to review the BLA. The regulatory agency pointed to the Chemistry, Manufacturing and Control (CMC) module as the area that needs the additional data. That has since been settled and the treatment could be approved in the U.S. within a month, and the European Union thereafter.

“The deep and durable responses observed in a large majority of patients in the KarMMa study published today in The New England Journal of Medicine demonstrate the potential of ide-cel to address a high unmet need for patients with heavily pre-treated and highly refractory multiple myeloma,” Nikhil C. Munshi, lead author of the research paper and Associate Director at The Jerome Lipper Multiple Myeloma Center at the Dana-Farber Cancer Institute said in a statement. “Despite the progress made in the treatment of multiple myeloma over the past decade, long-term disease-free survival is uncommon and relapses are inevitable. Currently, the patients who have progressed through the three main classes of therapy do not have very effective therapeutic options and their outcome are often poor.”

In addition to triple-class exposed RRMM patients, bluebird bio and Bristol Myers Squibb are also developing ide- in earlier lines of treatment for patients with multiple myeloma, including high risk newly diagnosed multiple myeloma.

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