Dive Brief:
- The Food and Drug Administration has cleared two multiple myeloma cell therapies for earlier use treating the blood cancer, granting expanded approvals to Bristol Myers Squibb's Abecma and to Johnson & Johnson's Carvykti.
- The OKs come three weeks after a panel of FDA advisers agreed the benefits of earlier treatment outweighed the risks, including concerns raised by agency reviewers over data indicating an elevated chance of death among treated study participants early on in the companies' main trials.
- Abecma, which is co-marketed by 2seventy Bio, is now available for people who previously received at least two drug regimens for their multiple myeloma, while Carvykti can be used after just one prior line of therapy. J&J developed Carvykti together with Legend Biotech.
Dive Insight:
Overall, trial results showed that both Abecma and Carvykti substantially reduced the risk of disease progression or death, compared to standard regimens. But the safety concerns raised by the FDA were enough to put Friday's approvals somewhat in question.
Seeking advice, the FDA in mid-March convened an expert committee to debate earlier use of the therapies. Ultimately, they found the benefits of both to be substantial enough to look past the early death risk raised by the FDA, voting 11-0 in favor of Carvytki and 8-3 in support of Abecma.
In responding to the FDA's concerns, Bristol Myers had cited patient crossover from the control arm to treatment as confounding survival data. The advisory panel also noted complications with the “bridging” therapy used prior to CAR-T treatment, which may be different in clinical practice than in a trial.
Treatment benefit “is significant and offers our patients a chance of significant time off therapy with associated quality of life improvement,” said Christopher Lieu, a panelist and associate medical professor at the University of Colorado, at the March 15 meeting. “But it’s a closer margin than I think we would like, and patients will need to have in-depth discussions about the risks and benefits.”
Both therapies target a protein called BCMA that’s found on malignant B cells in people with multiple myeloma. Their earlier approvals for later-line treatment added another option to a growing arsenal of therapies that have helped improve outcomes for patients with the blood cancer.
Still, people with multiple myeloma often relapse or their cancer becomes resistant to one treatment, requiring a switch to different regimens.
Abecma was previously cleared for relapsed or refractory disease in adult patients who have received four or more prior regimens, including ones that involve three of the main classes of multiple myeloma drugs.
Now, Abecma can be used in after two lines of therapy, provided patients are “triple class-exposed,” or have received treatment that includes those three types of drugs.
Carvytki can be used even earlier, as soon as after a patient's first relapse. The label specifies treatment for people who have received at least one line of therapy that includes a so-called proteasome inhibitor and an immunomodulatory drug. Patients' disease must be resistant to treatment with a drug called Revlimid.
"This product label difference offers significant commercial advantage for Carvykti as its eligibility for use in [second-line multiple myeloma] patients should limit the use of other BCMA CARTs in the following lines of therapy," wrote Jefferies analyst Kelly Shi in an April 7 client note.
CAR-T therapies are personalized, built from the immune cells of each individual patient. Manufacturing is complex and can be challenging to get right every time. Bristol Myers said it has a manufacturing success rate of 94% providing Abecma in the commercial setting, while J&J said it aims to double production capacity this year.
In addition to granting Carvykti an expanded approval, the FDA also cleared more favorably manufacturing specifications, according to Shi.
Editor’s note: This story has been updated to reflect the late Friday approval by the FDA of J&J’s Carvykti.