With an advisory committee meeting slated for Friday, the regulator has posted briefing documents in which it has raised concerns about early deaths in patients treated with Bristol Myers Squibb’s Abecma and Johnson & Johnson’s Carvykti.
Pictured: Exterior of the FDA headquarters in Maryland/ iStock/Grandbrothers
Bristol Myers Squibb’s Abecma and Johnson & Johnson’s Carvykti may be facing potential resistance from the FDA as the respective CAR-T therapies head into Friday’s advisory committee meeting with the regulator’s panel of outside experts, according to briefing documents from the FDA’s staff.
The agency is interested in the advisory committee’s opinion regarding the “higher rate of early deaths” for both Abecma and Carvykti in their respective trials, the documents state.
For Abecma, the document noted that there was a higher rate of early deaths in the treatment arm of the trial.
“The adequacy of exploratory analyses of the KarMMa-3 trial to support the identification of strategies to mitigate this risk warrants further discussion. Retrospective subgroup analyses, which are not pre-specified at the initiation of the study and not supported by an adequate sample size, cannot adequately characterize a heterogeneous patient population,” the FDA staff stated in the document.
The regulator also said that an analysis of the reasons for death is varied but includes an “inability to proceed with the first treatment step” as well as leukapheresis, manufacturing failure, disease progression and adverse events, among other reasons.
In the Carvykti briefing document, the FDA said the trial that was conducted—Cartitude-4—has shown “early detriment” in overall survival in the treatment arm, and an increased rate of early death is reflected in the Kapan-Meier curves as a “crossing hazards pattern favoring the standard therapy arm up to approximately 11 months; heavy censoring limits the estimation of the treatment effect on overall survival after 11 months.”
However, J&J remains positive about the trial results going into Friday’s advisory committee meeting.
“We are confident in the data from the Phase III Cartitude-4 study and look forward to reviewing survival and safety data with the FDA Oncologic Drugs Advisory Committee,” Brian Kenney, the global oncology and R&D communication leader at J&J, told BioSpace in an emailed statement. “We are committed to working with the FDA in the continued clinical development of Carvykti with a focus on bringing this immunotherapy to patients with multiple myeloma earlier in the course of the disease. We remain confident that the overall benefit-risk profile of Carvykti remains favorable in treating patients with relapsed/refractory multiple myeloma.”
BMS was not immediately available to respond to BioSpace’s request for comment.
Friday’s advisory committee meeting comes as the FDA has been looking deeper into the safety issues around CAR-T therapies. Since November of last year, the agency has been investigating the risk of secondary malignancies in patients who have received CD19-directed or BMCA-autologous CAR-T therapies. Global regulators are also increasingly scrutinizing the therapies.
Tyler Patchen is a staff writer at BioSpace. You can reach him at tyler.patchen@biospace.com. Follow him on LinkedIn.
