The FDA has identified increased mortality rates linked to two CAR-T therapies: Carvykti, made by Janssen Biotech, and Abecma, from Bristol-Myers Squibb K.K.
The findings have prompted the agency to prepare a brief for its Oncologic Drugs Advisory Committee that will convene again March 15 to ask "is the risk of early death associated with [CAR-T] treatment acceptable in the context of the clinical benefit?" according to documents it prepared ahead of the meeting.
The agency has prepared two documents, one on Carvykti and another on Abecma. While the FDA is raising concerns about both CAR-T therapies, data on Abecma seems to be worse.
The agency's review of Carvykti revealed an increased preliminary death risk of 8%, but its survival benefits have increased over time, according to the documents.
"Because of the higher rate of early deaths in the cita-cel arm, it is unclear whether the overall benefit-risk assessment is favorable; specifically, whether additional data is needed to support such an assessment," the agency wrote.
Abecma, meanwhile, was linked to a 9% increased preliminary death risk, and the FDA's investigation into it revealed that it "demonstrated a statistically significant effect on (progression-free survival), but a higher rate of early deaths," the agency wrote in its report, adding that "because of the higher rate of early deaths in the ide-cel arm, it is unclear whether the overall benefit-risk assessment is favorable."
The FDA's investigation into CAR-T therapies was prompted by 22 reports of patients contracting blood cancer after receiving CAR-T therapy treatments. The agency subsequently called for warning labels on all commercial CAR-T therapy products amid its investigation, and in January it sent letters to six manufacturers to inform them. Both Janssen and Bristol-Myers Squibb were among those recipients.
Becker's reached out to Janssen Biotech and Brisol-Myers Squibb for comment, and received the following responses:
A Janssen spokesperson said the company is "confident in the data from the Phase 3 Cartitude-4 study and look forward to reviewing survival and safety data with the FDA Oncologic Drugs Advisory Committee," and that they believe "the overall benefit-risk profile of Carvykti remains favorable in the treatment of patients with relapsed/refractory multiple myeloma."
A spokesperson for BMS told Becker's it is also "confident in the safety profile and clinical value of our cell therapies and [is] committed to ongoing transparency with all stakeholders." The company spokesperson also stressed that patient safety continues to be a top priority and in trials that Abecma "significantly improved durable outcomes with a well-established and consistent safety profile in earlier lines of therapy for patients with triple-class exposed relapsed or refractory multiple myeloma."