Eyes On Novartis, Gilead, Bristol Myers As FDA Weighs Risks Vs. Benefits Of Approved CAR T-Cell Therapies

Tuesday, the FDA said it received reports of patients developing T-cell malignancies, including chimeric antigen receptor CAR-positive lymphoma, in patients who received treatment with BCMA- or CD19-directed autologous CAR T cell immunotherapies.

The FDA has determined that the risk of T-cell malignancies applies to all currently approved BCMA-directed and CD19-directed genetically modified autologous CAR T-cell immunotherapies. Since 2017, six CAR T-cell therapies have been approved by the FDA:

• Bristol Myers Squibb & Co's BMY Breyanzi (lisocabtagene maraleucel)
• 2seventy Bio Inc TSVT and Bristol Myers Squibb's Abecma (idecabtagene vicleucel)
• Johnson & Johnson's JNJ Carvykti (ciltacabtagene autoleucel)
• Novartis AG's NVS Kymriah (tisagenlecleucel)
• Gilead Science Inc's GILD Yescarta (axicabtagene ciloleucel) and Tecartus (brexucabtagene autoleucel).

The agency said it's weighing "the need for regulatory action" in response to clinical testing and safety monitoring reports tied to commercial use. 

The identified risk applies to all approved CAR-T therapies, although the agency noted that "the overall benefits of these products continue to outweigh their potential risks for their approved uses."

The therapies are built from a patient's T cells, collected, and then genetically engineered with a chimeric antigen receptor (CAR) aimed at certain protein flags found on malignant cells. 

Once reinfused, the CARs recognize and bind to specific proteins, or antigens, on the surface of cancer cells.

Recently, Bristol-Myers Squibb's and 2seventy Bio's efforts to win expanded U.S. approval for its Abecma gene therapy hit a delay.

Citing RBC analysts, Reuters noted the concerns could be higher for Novartis' Kymriah and extremely rare for all the other marketed CAR-Ts.

"We are confident in the overall safety profile of both Tecartus and Yescarta," Gilead told Reuters in an emailed statement.

William Blair writes that the FDA needs more information to know how common CAR+ T-cell lymphomas are. 

However, if ongoing research shows that the treatment remains effective for a long time without needing more treatment, it could greatly help people with autoimmune conditions. 

People with healthy immune systems can remove these cells naturally. This seems likely because CAR-T cells tend to last for a shorter time in autoimmune conditions compared to cancers like lymphomas and multiple myeloma.