Trial sets up earlier use of J&J's Carvykti in myeloma

BCMA-directed cell therapy Carvykti (ciltacabtagene autoleucel) has seen sluggish growth since it was first approved by the FDA in March 2022 as a fifth-line or later therapy for multiple myeloma, but the CARTITUDE-4 study could see it used earlier on in the treatment pathway.

The study which tested Carvykti in patients with one to three lines of prior therapy gives J&J an opportunity to leapfrog Bristol-Myers Squibb and 2Seventy bios rival BCMA CAR-T therapy Abecma (idecabtagene vicleucel), currently also indicated as a fifth-line or later therapy for the blood cancer.

The Legend Biotech-partnered CAR-T hasnt yet reached sales levels that warrant being reported in J&Js quarterly results in part because of manufacturing problems but J&J said in its first-quarter results update last week that it expects the threshold to be reached in the first quarter of this year.

Legend said last week that Carvykti made $55 million in the fourth quarter. Abecma meanwhile, which came to market around a year before Carvykti, saw sales top the $100 million level in the third quarter of 2022, taking its nine-month tally to $263 million. BMS is due to report fourth quarter results on 2 February.

CARTITUDE-4 compared Carvykti to a pair of three-drug multiple myeloma regimens pomalidomide, bortezomib, and dexamethasone (PVd) or daratumumab, pomalidomide, and dexamethasone (DPd) in patients who had relapsed after at least one regimen containing lenalidomide, a standard first-line therapy for the cancer.

The study was unblinded on the recommendation of its independent data monitoring committee after a significant improvement in progression-free survival (PFS) was seen in the Carvykti group.

J&Js chief executive Joaquin Duato said during the companys first-quarter call that multiple myeloma will be the most important driver for its pharma division in the coming years.

Expanding the use of Carvykti is a key component of that, along with moving anti-CD38 antibody Darzalex (daratumumab) into first-line treatment and growing its two bispecific antibodies, recently-approved BCMAxCD3 drug Tecvayli (teclistamab) and recently-filed GPRC5DxCD3 candidate talquetamab.

BMS is also hoping to move Abecma into earlier lines of therapy for multiple myeloma of course, and last August reported encouraging results from the KarMMa-3 study is designed to support third-line treatment with the CAR-T, after failure of both lenalidomide and Darzalex treatment.

The final results of CARTITUDE-4 will be reported at a future medical congress, including results on overall survival, a secondary endpoint. That should allow some comparisons to be drawn between Carvykti and Abecma in earlier treatment.

Some analysts are already predicting blockbuster sales of J&Js CAR-T if it can obtain swift approval in the second-line setting, a population estimated to be around 36,000 patients per year versus around 3,000 for fifth-line use.

Meanwhile, both J&J and BMS are testing their CAR-Ts as first-line therapy respectively in the CARTITUDE-5/CARTITUDE-6 and KarMMa-9 trials which got underway last year.