FDA advisors have said that two BCMA-targeted CAR-T therapies can be used earlier in the treatment pathway for multiple myeloma, setting up FDA approvals for use in a broader patient population.
The Oncologic Drugs Advisory Committee (ODAC) has concluded that the efficacy of Johnson & Johnson/Legend Biotech’s Carvykti (ciltacabtagene autoleucel) and Bristol Myers Squibb/2seventy bio’s Abecma (idecabtagene vicleucel) outweigh their side effects in earlier lines of therapy for the blood cancer.
Both CAR-Ts are currently approved as fifth-line or later therapies for multiple myeloma, making them an option for around 5,000 patients out of an estimated 32,000 total cases per year in the US. Moving into second- or third-line use could double or triple the potential patient population.
First up for the ODAC deliberations was Carvykti, which is being reviewed for second-line or later use on the strength of the CARTITUDE-4 trial.
The ODAC was won over by the results, which showed that Carvykti reduced the risk of progression or death by an impressive 74% compared to standard therapy in patients who had stopped responding to lenalidomide, voting by 11 to 0 that the risk-benefit profile supported approval.
They were less convinced by the data on Abecma as a third-line or later therapy in the KarMMA-3 study, which showed the treatment cut the risk of disease progression or death by 51%, voting by 8 to 3 in favour of the CAR-T.
The FDA’s reviewers had raised some concerns about the therapies, including no effect on overall survival at the latest patient follow-up, a slight excess in the number of early deaths compared to standard therapy, and questions about the durability of the progression-free survival (PFS) benefit.
Last year, the FDA launched an investigation into the risk of secondary cancers in patients treated with BCNMA- or CD19-targeted CAR-Ts, and now requires a boxed warning on their labels.
Overall, however, panellists concluded that the benefits of the therapies outweighed those risks and they have the potential to be life-saving.
The FDA is due to decide on Carvykti by 5th April, but has not yet set a new deadline for Abecma since BMS’ marketing application was delayed by a request for new data last November. The latter is already approved for third-line or later use based on the KarMMA-3 data in Switzerland and Japan.
Even if approved, the two CAR-Ts – which require an involved therapeutic process that involves harvesting, modifying and re-infusing cells – could face serious competition from off-the-shelf alternatives like BCMA-targeting bispecific antibodies and antibody-drug conjugates.
Thos include J&J’s Tecvayli (teclistamab) and Pfizer’s Elrexfio (elranatamab), two BCMAxCD3 bispecifics already approved for later-line use but in testing to move forward in the treatment pathway, as well as GSK’s ADC Blenrep (belantamab mafodotin) which was withdrawn from sale in the US but has bounced back with new second-line data.
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