CAR-T-BCMA(Immunotech Biopharm Ltd.)

The FDA has expanded the label for Johnson & Johnson and Legend Biotech's Carvykti (ciltacabtagene autoleucel) to make it a treatment option for multiple myeloma patients after just one prior line of therapy.The decision, which follows a recent positive vote from an FDA advisory committee, allows the BCMA-targeting CAR-T cell therapy to be prescribed much sooner in the treatment paradigm, compared to its initial approval back in 2022 when it was cleared for fifth-line use.Carvykti's latest win comes on the heels of the FDA approving CAR-T rival Abecma (idecabtagene vicleucel), co-developed by Bristol Myers Squibb and 2seventy bio, in the third-line setting for relapsed or refractory multiple myeloma.Johnson & Johnson's supplemental filing was supported by the Phase III CARTITUDE-4 study, which evaluated Carvykti versus standard regimens in adults with relapsed and lenalidomide-refractory multiple myeloma who had received one to three prior lines of therapy. Carvykti reduced the risk of disease progression or death by 59% compared to standard regimens, meeting the primary endpoint.Meanwhile, an interim analysis done at the November 2022 cutoff showed a benefit of 22% with Carvykti on the key secondary measure of overall survival (OS). According to briefing documents released by the FDA last month, that rate improved to 43% by December 2023 when half of the 250 planned OS events needed for the final analysis had occurred.Label details early deathsLike Abecma, Carvykti's warning label details an imbalance in early deaths in its pivotal study. Within the first 10 months of randomisation of CARTITUDE-4, 14% of patients in the Carvykti arm experienced early deaths, compared to 12% for controls. Among the 29 early deaths with Carvykti, 10 occurred before infusion, all due to disease progression, while 19 occurred after infusion, with 3 due to disease progression and 16 due to adverse events, mainly infections.The drug's boxed warning was also updated to include secondary haematological malignancies, following a request by the FDA earlier this year that affected CAR-Ts as a class.Tyrone Brewer, president of US haematology at Johnson & Johnson Innovative Medicine, said the company has been ramping up efforts to boost supplies. "We more than doubled manufacturing of Carvykti in 2023, we are striving to double again in 2024, and we will continue to invest in our capacity."