Bristol Myers, Bluebird Bio Seek FDA Approval of Ide-cel to Treat Advanced Multiple Myeloma

Bristol Myers Squibb and Bluebird Bio are seeking U.S. approval of their lead investigational CAR T-cell therapy — idecabtagene vicleucel (ide-cel; bb2121) — for the treatment of heavily pre-treated multiple myeloma.

The companies have submitted a biologics license application to the U.S. Food and Drug Administration for ide-cel’s approval to treat adult patients, who have received at least three prior lines of cancer therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody.

Chimeric antigen receptor T-cell therapy, more commonly known as CAR T-cell therapy, is a type of immunotherapy in which a patient’s T-cells — immune cells with anti-cancer activity — are collected and re-engineered in the lab to better recognize and eliminate cancer cells. The modified cells are heavily expanded in the laboratory and then infused back into the patient.

Ide-cel (bb2121) is a type of CAR T-cell therapy that uses genetically-modified human T-cells that specifically recognize and eliminate cancer cells containing the B-cell mature antigen (BCMA) — a protein found on the surface of myeloma cells and considered one of the best targets for this therapy — in people with multiple myeloma, while leaving healthy cells unharmed.

The therapy previously received the designation of priority medicines, or PRIME, from the European Medicines Agency and breakthrough therapy from the FDA for the treatment of relapsed and refractory multiple myeloma. Ide-cel is also the first BCMA CAR T-cell therapy for which regulatory approval has been requested to treat multiple myeloma.

The companies’ submission was based on data from a pivotal, open-label, Phase 2 trial (NCT03361748) called KarMMa. The trial assessed the safety and efficacy of ide-cel in patients with relapsed and refractory multiple myeloma who received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody, and who failed to respond to their last treatment regimen.

The study’s main goal was to assess the percentage of patients responding to treatment within two years of receiving an infusion of ide-cel (overall response rate). Secondary goals included assessing the percentage of patients attaining complete responses (complete cancer eradication), response duration, and time to response.

Topline data from KarMMa showed that at a median follow-up of 11.3 months, approximately 73.4% of patients responded to treatment, with 31.3% achieving complete responses, within a period of two years. The median duration of response was 10.6 months.

The therapy’s safety profile was consistent with findings from CRB-401 (NCT02658929), a Phase 1 trial that assessed the preliminary safety and efficacy of ide-cel. Full data from KarMMa will be presented at an upcoming medical meeting.

In addition to KarMMa, three other clinical trials — KarMMa-2 (NCT03601078), KarMMa-3 (NCT03651128), and KarMMa-4 (NCT04196491) — are currently investigating the safety and efficacy of ide-cel when used as an earlier line of treatment, including in newly diagnosed patients with multiple myeloma.

In a recent investor fact sheet, Bristol Myers Squibb stated that patient screening, enrollment, and apheresis (the process of collecting and separating patients’ T-cells) in its cell therapy trials have been suspended due to the COVID-19 outbreak.

However, this decision does not include the KarMMa trial, for which patient enrollment has been completed, nor does it affect ide-cel’s regulatory process.

“The decision to temporarily suspend further screening, enrollment and apheresis is not considered an urgent safety measure and does not impact the ongoing Biologics License Application (BLA) activities with the U.S. FDA for idecabtagene vicleucel (ide-cel, bb2121) or lisocabtagene maraleucel (liso-cel, JCAR017) [in development for the treatment of diffuse large B-cell lymphoma],” the company stated. “The clinical trials that form the basis for these applications have completed enrollment.”