The U.S. Food and Drug Administration (FDA) asked for more information from Bristol Myers Squibb and Bluebird Bio as it considers a request to approve their lead CAR T-cell therapy — idecabtagene vicleucel (ide-cel; bb2121) — for heavily pre-treated patients with multiple myeloma.
The agency’s refusal letter requested further details on the potential therapy’s chemistry, manufacturing and control — or CMC module, necessary to ensure treatment safety, quality and potency — to continue the review process, the companies reported. No further clinical or preclinical data was specified.
BMS is planning to resubmit the BLA with the required information by the end of July.
In the original BLA, the companies requested ide-cel (bb2121) be approved to treat adults with relapsed and refractory multiple myeloma who had undergone at least three prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody.
Ide-cel is designed to use genetically modified human T-cells to recognize and eliminate cancer cells containing the B-cell mature antigen (BCMA) — a protein found on the surface of cancer cells — in people with multiple myeloma, while leaving healthy cells unharmed.
The submission was based on data from the open-label Phase 2 KarMMa trial (NCT03361748), currently investigating the safety and efficacy of ide-cel in 140 patients with advanced multiple myeloma after at least three prior therapies and who failed to respond to their last treatment regimen.
Topline data from KarMMa showed that among the 128 patients treated at the target dose of 150-450 x 106 CAR T-cells, 73.4% responded to treatment at a median follow-up of 11.3 months, with 31.3% achieving complete responses (full cancer eradication) within two years. Treatment responses lasted a median of 10.6 months. Median progression-free survival (PFS), defined as the time patients lived without any signs of disease progression or death, was 8.6 months.
Most patients (83.6%) in KarMMa experienced cytokine release syndrome, a serious immune reaction. CRS is a condition in which large amounts of cytokines — molecules that mediate immune and inflammatory responses — produced by engineered T-cells lead to an overactivation of the immune system. It can happen in response to certain types of cancer immunotherapy, including CAR T-cell therapy.
The condition was severe, life-threatening, or fatal in 5.5% of these cases.
Ide-cel is also being investigated as an earlier line of treatment for multiple myeloma in three other clinical trials — KarMMa-2 (NCT03601078), KarMMa-3 (NCT03651128), and KarMMa-4 (NCT04196491) in newly diagnosed patients.
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