FDA removes REMS for all autologous CAR T-cell immunotherapies

Risk Evaluation and Mitigation Strategy (REMS) program

Formalized in 2007, the FDA's REMS drug safety program provides guidelines for medications with a high potential for serious adverse effects. The regulatory framework is designed to promote product safety by ensuring that the benefits of certain prescription drugs outweigh their risks.

As a result of the FDA's decision, the REMS program requirements for the following approved gene therapies have been removed:

• Abecma (idecabtagene vicleucel). Treats relapsed or refractory multiple myeloma.
• Breyanzi (lisocabtagene maraleucel). Treats large B-cell lymphoma, small lymphocytic lymphoma, follicular lymphoma, mantle cell lymphoma and relapsed or refractory chronic lymphocytic leukemia.
• Carvykti (ciltacabtagene autoleucel). Treats relapsed or refractory multiple myeloma.
• Kymriah (tisagenlecleucel). Treats relapsed or refractory B-cell precursor acute lymphoblastic leukemia, large B-cell lymphoma and follicular lymphoma.
• Tecartus (brexucabtagene autoleucel). Treats mantle cell lymphoma or acute lymphoblastic leukemia.
• Yescarta (axicabtagene ciloleucel). Treats large B-cell and follicular lymphoma.

Industry implications

Because the FDA has removed REMS requirements for these CAR T-cell therapies, hospitals and clinics no longer need special certification or immediate on-site access to tocilizumab for managing cytokine release syndrome. The agency determined that risks such as CRS and neurological toxicity can be effectively addressed through existing labeling, including boxed warnings and medication guides.

"Eliminating the REMS that is no longer needed also expedites the delivery of potentially curative treatments to patients and reduces burden on providers," Prasad suggested.

Since the first CAR T-cell therapy approval in 2017, more than 30,000 patients with blood cancers have been treated with these immunotherapies in the United States alone. The FDA said the removal of REMS requirements is expected to maintain safety while improving access to advanced cancer treatments.

"Physicians and institutions now have greater experience identifying and managing toxicities with the currently approved CAR T products," Richard Pazdur, M.D., FDA Oncology Center of Excellence Director, said in the press release. "This approach will potentially facilitate patient access to these treatments while continuing to prioritize safety."

Continued safety monitoring

The FDA stated that ongoing safety monitoring of all biologics, including CAR T-cell therapies, will be prioritized and that the public will be updated as new information emerges.

Although REMS requirements have been removed for these gene therapies, manufacturers are still required to report adverse events under 21 CFR 600.80 and conduct long-term post-marketing safety studies, including 15 years of follow-up to assess risks such as secondary malignancies.

Alivia Kaylor is a scientist and the senior site editor of Pharma Life Sciences.