FDA panel backs broader use of J&J, Bristol Myers cell therapies for myeloma

Advisers to the Food and Drug Administration have endorsed the use of two cellular medicines for multiple myeloma earlier in a patient’s disease, overlooking safety concerns raised by agency reviewers earlier this week.

The advisory committee on Friday voted unanimously, 11-0, that the benefits of Johnson & Johnson and Legend Biotech’s Carvykti outweighed the risks when administered to patients as early as after their first relapse. They cast a narrower, but similarly positive vote, 8-3, for Bristol Myers Squibb’s Abecma. 

The impact ot treatment “is significant and offers our patients a chance of significant time off therapy with associated quality of life improvement,” said Christopher Lieu, an associate medical professor at the University of Colorado, who voted in favor of Abecma and Carvykti. “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.” 

The votes increase the likelihood that use of both therapies, which are currently available to myeloma patients following at least three lines of treatment, will be expanded in the U.S. European regulators have already endorsed such a decision. The FDA doesn’t always follow the advice of its advisory committees, but usually does. 

The panel threw their support behind Carvykti and Abecma based on studies showing they helped people with the blood cancer live longer without their disease progressing when compared to standard drug regimens.

In doing so, panelists waved off concerns flagged by FDA reviewers in briefing documents posted earlier this week. In those documents, the agency cited an increased risk of early death in patients who received Carvykti or Abecma. Specifically, FDA statisticians found a higher risk of death in patients who’d received Carvykti in the first 11 months of the study supporting its application. For Abecma, that elevated risk lasted 15 months. 

While acknowledging the FDA’s findings, some experts countered that patients would likely choose treatment anyway given the length of the remissions observed in testing of Carvykti and Abecma.

“The question is whether or not the patients are willing to undertake the risk,” Lieu said following the positive Carvykti vote. “The answer will likely be ‘yes’ for patients who may want just a chance at a longer time off treatment.”

The FDA, for its part, noted that the therapies haven’t yet clearly shown they can extend lives. “It may be when the data are more mature, but it’s not there yet,” said Robert Sokolic, the head of the agency branch that reviews hematology drugs.

Agency staff also claimed that the early deaths in testing weaken the overall results and purported long-term benefits of treatment. The known side effects of CAR-T therapy, as well as the conditioning regimens used to prepare patients for treatment, may have elevated patients’ death rates in testing, making the benefits of therapy less clear.  

“All these risks should be considered integral to the benefit-risk assessment of CAR-T cell therapy,” Helkha Peredo-Pinto, an FDA clinical reviewer, told committee members.

However, Jordan Schecter, J&J’s vice president of R&D, argued that the picture would look different outside the confines of a clinical trial. Some of the early deaths in testing could have been averted if physicians had been able to give patients the best possible “bridging” therapy while they awaited CAR-T treatment. The complex therapies take weeks to manufacture, during which time patients’ disease can progress.  

The increased risk of early deaths in the trials “need to be explained,” said Brian Durie, the chairman of the International Myeloma Foundation. But “the key point for me is that it was occurring in this preparatory period,” and was “not associated with the CAR-T therapy itself.”

Jorge Nieva, an associate medical professor at University of Southern California, added that other cancer therapies, such as stem cell transplants, have a “front-loaded” risk of death but better long-term outcomes than alternative treatments.

But Nieva, along with other panel members, agreed that the issues surrounding the use of bridging therapy in testing shouldn’t be as much of a problem in clinical practice. Physicians won’t be burdened by clinical trial rules that delay CAR-T treatment and restrict bridging therapies, he said.

“A reason for some of the problems here is, in a way, an artifact of the clinical trial process,” he said. “In the real world, where collection and manufacturing could occur early in the course of disease, that may be less of an issue for patients.”

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