FDA Drops REMS Requirement for 6 Approved CAR T-Cell Therapies
The FDA made the move with the view that the REMS are no longer necessary to ensure a favorable risk-benefit-ratio for the products and that dropping the requirement may increase accessibility to these therapies.
The FDA is no longer requiring Risk Evaluation and Mitigation Strategies (REMS) for the 6 CD19/BCMA-directed chimeric antigen receptor T-cell (CAR-T) therapies that are approved by the agency.1
The 6 products include Bristol Myers Squibb (BMS) and 2seventybio’s idecabtagene vicleucel (ide-cel; marketed as Abecma); BMS’s lisocabtagene maraleucel (liso-cel; marketed as Breyanzi); Janssen and Legend Biotech’s ciltacabtagene autoleucel (cilta-cel; marketed as Carvykti); Novartis’s tisagenlecleucel (tisa-cel; marketed as Kymriah); Kite Pharma’s brexucabtagene autoleucel (brexu-cel; marketed as Tecartus); and Kite Pharma’s axicabtagene ciloleucel (axi-cel; marketed as Yescarta). The FDA made the move with the view that the REMS are no longer necessary to ensure a favorable risk-benefit-ratio for the products and that dropping the requirement may increase accessibility to these therapies.
“The FDA has taken the bold step to remove the REMS requirement from giving CAR-T therapies,” Vinay Prasad, MD, MPH, the chief medical and scientific officer and the director of the Center for Biologics Evaluation and Research at the FDA, said in a statement.1 “REMS is a useful safety system, but reevaluation over time helps inform whether a REMS is still needed to ensure that the benefits of a product outweigh its risks. Eliminating the REMS that is no longer needed also expedites the delivery of potentially curative treatments to patients and reduces burden on providers.”
With the removal of the REMS requirement, hospitals and clinics that provide these therapies no longer necessitate a specific certification. Additionally, these centers are no longer required to have on-site tocilizumab immediately accessible.
“Physicians and institutions now have greater experience identifying and managing toxicities with the currently approved CAR-T products,” Richard Pazdur, MD, the FDA Oncology Center of Excellence director, added to the statement.1 “This approach will potentially facilitate patient access to these treatments while continuing to prioritize safety.”
Safety monitoring for the affected products will continue in the form of adverse event reporting according to established protocols. The existing requirements for postmarketing observational safety studies assessing secondary malignancy risks and long-term safety follow-up also remain in place.
Alongside removal of the REMS requirement, the FDA also made changes to the labels for liso-cel and ide-cel.2 Notably, BMS released a statement celebrating the FDA’s decision, pointing out that logistical and geographic barriers have likely hindered some patients ability to receive CAR-T that the FDA’s changes to the labels for liso-cel and ide-cel should make the products more accessible. The company noted that historically only about 2 in 10 eligible patients are treated with CAR-T products. BMS highlighted that the FDA’s labeling change reduces the requirement for patients to be located near a healthcare facility for 4 weeks posttreatment down to 2 weeks after treatment with BMS’s CAR-T products.
"Living with blood cancer is challenging, but patients and their loved ones still need to maintain jobs, take care of families, and plan for the future,” Sally Werner, the chief executive officer of Cancer Support Community, said in the BMS press release.2 “Today’s announcement reduces some of the most onerous requirements that may have previously discouraged patients, particularly those who live far from a treatment center, from seeking the potentially transformational effects of cell therapy. We applaud any and all efforts to continue to break down barriers, reducetime burden on patients and caregivers, and increase uptake of this life-saving therapy."
