J&J, Legend's Carvykti hits goal in earlier myeloma, escalates CAR-T showdown with Bristol Myers' Abecma

The BCMA CAR-T battle between Bristol Myers Squibb’s Abecma and Johnson & Johnson and Legend Biotech’s Carvykti is about to get more serious.

Friday, Legend and J&J said the closely watched phase 3 CARTITUDE-4 trial has hit its goal at an interim analysis. That means Carvykti topped existing standard combination therapies at staving off tumor progression or death in patients with multiple myeloma who had received one to three prior lines of therapy.

The success of CARTITUDE-4 was largely expected given Carvykti’s impressive near-100% complete response rate and long response duration in the late-line myeloma setting. Pending detailed data, it could escalate Carvykti’s threat against BMS and 2seventy bio’s Abecma as both medicines pursue approvals in earlier lines of treatment.

Both Carvykti and Abecma are now only allowed as fifth-line therapies. But J&J's ambitions in earlier myeloma treatment have led the company to aggressively project that Carvykti could reach over $5 billion in peak sales. First, CARTITUDE-4 needs not just to succeed but to dazzle.

Before the Carvykti announcement, BMS already revealed the success of the phase 3 KarMMa-3 trial, which is testing Abecma in myeloma patients who had tried two to four prior regimens.

Compared with investigator’s choice of combination therapies, Abecma cut the risk of disease progression or death by 51%, according to data shared in an abstract at the upcoming European CAR T-cell meeting. Patients who got Abecma went a median 13.3 months without disease progression versus 4.4 months for standard treatments. Detailed analyses will be shared in February.

Industry watchers won’t be able to directly compare CARTITUDE-4 and KarMMa-3 because the Carvykti trial tested the Legend and J&J CAR-T one treatment line earlier. Another key difference is that the Abecma trial required patients to have tried a powerful CD38 antibody like J&J’s Darzalex, but the Carvykti study didn’t.

For an earlier treatment setting, industry watchers naturally expect more efficacy. In a Sunday note to clients, Cowen analysts said they expect the absolute median progression-free survival time to look better for Carvykti than Abecma, and that the reduction in progression risk should “at least be in the same ballpark” as the BMS trial in a later-line setting.

Eventually, Carvykti needs to post at least 36 months of median progression-free survival (PFS) to trigger “substantial uptake” in second- to fourth-line multiple myeloma, the Cowen team said.

Carvykti likely wouldn’t reach its median PFS at the interim analysis because of the short follow-up time, the Cowen team said. A statistical simulation by Cowen suggested that a minimum 35% PFS risk reduction would be sufficient for Carvykti’s CARTITUDE-4 to hit its goal at its interim. But the team expects the Legend-J&J CAR-T to eventually show a risk reduction in the range of 60% to 70% over standard triplets.

J&J and Legend said detailed CARTITUDE-4 data will be shared at an future medical meeting and will “support discussions with health authorities about potential regulatory submissions.”

For now, partly thanks to limited supply, Carvykti posted $55 million sales in the fourth quarter, flat over the third quarter, Legend reported earlier this week.

A second-line nod would unlock a market with about 36,000 patients per year in the U.S., three times that of Carvykti’s current fifth-line opportunity, according to Legend.

But frontline treatment represents an even larger pool, and both Legend-J&J and BMS are testing their CAR-Ts there. Carvykti’s CARTITUDE-5 and CARTITUDE-6 are in newly diagnosed patients who are ineligible and eligible, respectively, for stem cell transplant. BMS is launching the KarMMa-9 trial in newly diagnosed patients who have suboptimal response to transplant.