J&J, Legend's Carvykti bid for earlier multiple myeloma use will face FDA adcomm

Early evidence showing Carvykti’s potential to prolong patients’ lives in an earlier multiple myeloma setting didn’t save Johnson & Johnson and Legend Biotech’s CAR-T medicine from a public interrogation by the FDA.

The U.S. agency plans to convene its Oncologic Drugs Advisory Committee (ODAC) to discuss Carvykti’s data in multiple myeloma patients who have received at least one prior line of therapy, Legend disclosed Tuesday in a securities filing.

The announcement follows Bristol Myers Squibb’s disclosure in November that the FDA’s ODAC will meet to discuss the company’s rival CAR-T therapy, Abecma, for its own bid to treat earlier lines of relapsed or refractory multiple myeloma.

The FDA hasn’t shared a date for either planned meeting. It’s possible that the agency will combine the two reviews into one meeting given they’re both centered on BCMA CAR-T meds trying to move into earlier treatment of multiple myeloma. The FDA has previously set a target decision date of April 5 for the Carvykti application.

“We are very confident on the data of our phase 3 CARTITUDE-4 study that supports the efficacy and safety of Carvykti” in the earlier treatment of multiple myeloma, J&J CEO Joaquin Duato said Tuesday on the company’s fourth-quarter earnings call.

The ODAC move comes as the FDA flags a “serious” risk of patients developing secondary cancers following treatment with existing CAR-T therapies. The agency is looking to add a black-box warning about T-cell malignancies for all BCMA- and CD19-directed autologous T cell immunotherapies.

As a new safety signal, T-cell malignancies might sway the FDA’s benefit-risk assessment for CAR-T meds in earlier lines of treatment in what would be a “worst-case scenario,” Leerink Partners analysts said in a note in November. The Leerink team pointed to the upcoming Abecma advisory committee as “an important milestone in understanding evolving regulatory stances on non-relapse risks with CAR-T” therapies.

BMS has said that the Abcema meeting will focus on overall survival data from the KarMMa-3 study. Without adjusting for patient crossover between treatment arms, Abecma showed no life extension benefit—but a negligible 1% increased risk of death—compared with standard combination regimens when used after two to four prior lines of therapy, according to an updated interim analysis of KarMMa-3 presented in December.

The overall survival analysis was confounded by about 56% of patients in the control arm having crossed over to receive Abecma following disease progression on standard combos.

But Carvykti’s data look quite different. In an interim analysis of the CARTITUDE-4 trial, Carvykti was linked to a 22% reduction in the risk of death, although the data were immature when presented in June.

J&J will review updated overall survival and safety data during the upcoming ODAC meeting, Duato said on Tuesday’s call. Despite the safety concern, Duato maintained that Carvykti will reach more than $5 billion in peak sales. The drug pulled in $159 million in sales in the fourth quarter versus $152 million in the third quarter.

Outside the U.S., J&J and Legend expect a European Medicines Agency opinion on their earlier-line application in the first quarter of 2024, Duato said. The EU regulator will also convene a Scientific Advisory Group Oncology meeting to review the CARTITUDE-4 data, Legend said in its securities filing.