The much-anticipated CAR-T showdown between Bristol Myers Squibb and the alliance of Johnson & Johnson and Legend Biotech in the early treatment of multiple myeloma has arrived sooner than expected—courtesy of a data leak.
One infusion of J&J and Legend’s CAR-T therapy Carvykti slashed the risk of tumor progression or death by a whopping 74% compared with standard of care in patients with multiple myeloma who had previously tried one to three lines of therapy, according to an apparently leaked abstract Fierce Pharma has obtained.
Carvykti also conferred a positive trend toward extending patients’ lives. The BCMA-targeted cell therapy reduced the risk of death by 22%, although the analysis is likely immature and not statistically significant at this point.
The drug’s massive showing on the progression-free survival (PFS) marker puts BMS’ rival CAR-T therapy Abecma on notice. BMS’ cell therapy recently put up its own phase 3 trial win in earlier treatment of myeloma.
Although demand currently outstrips supply for both therapies, industry watchers figure Carvykti will eventually come out the winner in the rivalry.
Both J&J and Legend said they couldn’t comment on the data because of an embargo policy. The data were apparently mistakenly posted on the European Hematology Association’s annual congress website. The abstract suggests the data will first be presented at the American Society of Clinical Oncology’s annual meeting in June.
In a Wednesday note to clients, William Blair analyst Matt Phipps, Ph.D., called Carvykti’s new phase 3 CARTITUDE-4 data “impressive.” The result exceeded the already high expectations of analysts at Cowen, who in January projected Carvykti would show a PFS improvement between 60% to 70%.
This 74% showing is “game changing and ensures rapid uptake” upon a potential approval for Carvykti as a second-line treatment for multiple myeloma, the Cowen team wrote in a note Tuesday.
In CARTITUDE-4, patients in the control arm went a median 12 months without progression, matching Cowen’s model. The median PFS time wasn’t yet reached for Carvykti, but it has climbed above 23 months. Based on the 74% risk reduction, Cowen’s statistical model now pointed to almost 40 months of median PFS.
Cowen analysts have suggested that Carvykti could enjoy “substantial uptake” if it can improve median PFS by two years.
In its own phase 3 trial, dubbed KarMMA-3, BMS' Abecma reduced the risk of progression or death by 51% over standard combination therapies. That trial enrolled patients who had failed on two to four lines of prior therapy—one line later than CARTITUDE-4.
Another key difference between the two studies is that the Abecma trial enrolled patients who had failed on—and most were refractory to—three different classes of therapies. The Carvykti trial only required resistance to BMS’ Revlimid.
Based on KarMMA-3, the FDA has accepted an application for Abecma for earlier treatment of myeloma, with a target decision date set for Dec. 16. Both Abecma and Carvykti are currently only approved in the U.S. as fifth-line therapies.
Phipps expects Caryvkti could get an FDA approval one line earlier than Abecma because CARTITUDE-4 enrolled a meaningful number of patients who had just one prior line of treatment.
Although the two trials are different, the “results for Carvykti across the board continue to look like the drug will eventually be a headwind to Abecma adoption,” Phipps said. Cowen’s earlier estimates also suggest Carvykti will become the leading BCMA CAR-T drug.
Wall Street’s view of the two therapies also matches the drugmakers’ respective estimates for their own products. J&J has put Carvykti’s peak sales potential at above $5 billion, while BMS figures Abecma sales could reach around $1 billion.
The leaked CARTITUDE-4 data showed other bright spots for Carvykti. The drug showed a much higher rate of complete response compared with control (73% vs. 22%) as well as a higher rate of no minimal residual disease (61% vs. 16%). Both markers indicate long-term benefits.
All Carvykti batches were successfully made without manufacturing failures for this trial. That's significant, because current reports indicate around 30% out-of-specification rates for commercial doses of Carvykti.
In terms of safety, only 1% of Carvykti takers experienced grade 3 cytokine release syndrome. No grade 4 or 5 episodes were recorded.
Despite the strong data from Carvykti, William Blair’s Phipps believes Abecma won’t be affected in the near term. That’s because both therapies are in short supply in late-line treatment. The companies can basically sell all the doses that they can make.
Meanwhile, J&J and Legend just recruited another cell therapy veteran, Novartis, to help manufacture Carvykti for clinical trials outside of China. However, given the tech transfer and the requirement for FDA approval of the new manufacturing site, Phipps thinks the deal could take several years to fully affect supply.
Showing a sign of improvement in manufacturing capacity, Carvykti raked in $72 million sales in the first quarter of 2023, J&J and Legend said Tuesday. The number was up from $55 million in two consecutive quarters in the second half of 2022.
Legend’s stock price jumped nearly 20% in Wedensday morning’s trading, pushing the Chinese biotech’s market cap across the $10 billion threshold.
Editor's Note: The story has been updated with information from a Cowen note published on Tuesday.