Bristol Myers Squibb’s struggling CAR-T therapy Abecma has hit a major setback.
Bristol and its partner 2seventy bio have decided to pull the plug on the phase 3 KarMMa-9 trial. The trial had been evaluating Abecma as a first-line maintenance treatment in patients with newly diagnosed multiple myeloma who experienced a suboptimal response to a stem cell transplant.
The two companies attributed the decision to enrollment challenges. Having been open for more than a year in 18 countries, the study only accrued 10% of its enrollment target “despite numerous collaborative efforts with investigators and study staff to support recruitment,” BMS said in a release Wednesday. The trial was designed to enroll 618 subjects, according to a clincialtrials.gov entry.
Thanks to improved induction therapies, more than 70% of patients with newly diagnosed multiple myeloma can achieve a complete response or better after a transplant, Ann Kerber, BMS’ head of late clinical development of hematology, oncology and cell therapy, explained in a statement.
“We celebrate this progress for patients while also recognizing that it reduces the eligible patient population for, and viability of, the KarMMa-9 trial," Kerber added.
In a similar statement, 2seventy’s chief medical officer, Anna Truppel-Hartmann, noted the first-line myeloma landscape has improved considerably lately. With more use of quadruplet induction therapy, more aggressive consolidation therapies and optimized maintenance regimens, fewer patients are eligible for KarMMa-9 than when the trial was designed.
BMS and 2seventy said they will work with investigators to determine appropriate next steps for patients already enrolled in the KarMMa-9 study.
The first-line setback is another blow to Abecma in its ongoing competition with Johnson & Johnson and Legend Biotech’s rival BCMA CAR-T therapy Carvykti, a race that the BMS/2seventy med is already losing. After recent FDA nods, Carvykti has jumped into second-line treatment, while Abecma has only moved to third line. Carvykti recently reported an ability to prolong patients’ lives in that setting, while Abecma couldn’t say the same in its own third-line study.
After KarMMa-9, there are no phase 3 trials for Abecma in first-line treatment. BMS/2seventy currently do not have plans to start another phase 3, but the partners will “continue expanding the reach of Abecma to as many multiple myeloma patients as possible,” a 2seventy spokesperson told Fierce Pharma.
By comparison, J&J and Legend are running two phase 3 trials in first-line myeloma. The CARTITUDE-5 trial—for patients for whom stem cell transplant was not intended—has recently completed enrollment, Legend disclosed in August alongside its second-quarter earnings report.
As for the CARTITUDE-6 trial in transplant-eligible patients, the companies “fully expect” that enrollment will complete in 2026, Legend CEO Ying Huang, Ph.D., said during the firm’s second-quarter call. Then during an investor event earlier this month, Huang said the trial “should be able to finish” enrollment in 2025.
“We see a lot of demand, and this has enrolled very quickly,” Huang said of CARTITUDE-6.
CARTITUDE-6 is different from KarMMa-9. While the BMS/2seventy trial set out to test Abecma in patients who didn’t respond well to transplant, the J&J/Legend study is actually pitting Carvykti against transplant following induction therapy with a quadruplet regimen that includes J&J’s Darzalex.
First-line treatment is a major market for myeloma CAR-Ts. By Legend’s estimate, the CARITUTDE-5 and -6 trial settings cover about 52,000 patients annually.
Although the Carvykti trials have not faced difficulties in enrollment, the comments from BMS/2seventy serve as a reminder of how powerful first-line myeloma therapies have become and the high bar J&J/Legend will face to beat the current standard of care.
Meanwhile, Carvykti is beating Abecma on the commercial front. In the second quarter, global Abecma sales reached $95 million, including $54 million from the U.S., compared with $52 million stateside in the first quarter. In contrast, Carvykti brought in $186 million sales in the second quarter despite being later to the market.
On Wednesday, 2seventy said it expects third-quarter Abecma sales in the U.S. will grow 30% sequentially thanks to the recent FDA approval in the third line. Demand, as measured by patients under cell collection, is also expected to see double-digit growth, the Massachusetts biotech said.
BMS and 2seventy co-develop and co-commercialize Abecma in the U.S., while BMS is solely responsible for ex-U.S. markets.
The discontinuation of KarMMa-9 means additional revenues in the first-line will be out of reach, but 2seventy said the move will save it more than $80 million in costs over the next few years. This will help the biotech move faster to a break-even financial state in 2025.
Expectations for Abecma are low among investors, but getting more patients in the third-line setting “would offset concerns about the fixed costs of the cell therapy franchise,” William Blair analysts said in a Wednesday note to clients.
There will be no reduction in workforce at 2seventy as a result of the KarMMa-9 news, the 2seventy spokesperson said. The company has recently undergone significant makeovers, with divestments and layoffs leaving the firm focused on Abecma.