Restricted availability under an FDA-mandated drug safety program has limited the reach of CAR-T cell therapies for certain blood cancers—until now.
The FDA has removed the Risk Evaluation and Mitigation Strategies (REMS) requirements for currently approved BCMA- and CD19-directed CAR-T therapies, the agency said Thursday.
Existing commercial CAR-T products, including Bristol Myers Squibb’s Abecma and Breyanzi, Gilead Sciences’ Yescarta and Tecartus, Johnson & Johnson and Legend Biotech’s Carvykti, and Novartis’ Kymriah, stand to benefit from the update. Autolus’ CD19 CAR-T Aucatzyl was approved in November for B-cell precursor acute lymphoblastic leukemia without a REMS requirement. The FDA’s website only has updated prescribing information for Carvykti as of publication time, but the agency's announcement said the REMS requirements have been removed for all these drugs.
The FDA previously required the REMS safety program for each approved CAR-T drug because of the risk of cytokine release syndrome and neurological toxicities associated with the drugs.
Under the REMS program, hospitals and clinics had to be be specially certified to be able to administer CAR-T therapies.
Now, though, the FDA has determined that the demand is no longer necessary “[g]iven the established management guidelines and extensive experience of the medical hematology/oncology community in diagnosing and managing” the safety risks, according to an FDA approval letter (PDF) for Carvykti.
Post-treatment monitoring of patients no longer has to be carried out at certified healthcare facilities, according to the FDA. In addition, patients are now asked to remain within close proximity of a healthcare facility for two weeks, rather than the previously mandated four weeks.
Previously, patients were instructed to refrain from driving for at least eight weeks following infusion. Now, the new labels have shortened that period to two weeks.
“These changes should facilitate patient access, particularly for those who do not live near centers of excellence where CAR-Ts are commonly administered,” Citi analysts wrote in a Friday note.
“FDA expects that the REMS elimination, and these labeling updates, will help improve access to these products, particularly for patients who live in rural areas, while ensuring safe and effective administration to patients who need them,” the agency said in its announcement.
Following the FDA’s move, BMS said it has launched “a renewed effort to add community cancer centers nationwide to administer Breyanzi and Abecma closer to patients, helping further reduce travel time and duration of stay away from home, family and work.”
In a statement to Fierce Pharma, Gilead said the update “underscores the knowledge and experience that CAR T treaters have gained to safely administer these therapies,” and that the company is pleased the change “will help lessen the burden on HCPs and patients, enabling more people to receive these potentially curative treatments.”
The REMS requirements were a major burden that discouraged referrals from community doctors and affected patients’ willingness to receive a CAR-T drug, Leerink Partners analysts wrote in their own Friday note, citing two blood cancer experts. One expert told Leerink that he would expect reduced monitoring requirements and driving restrictions would double the current uptake of CAR-T therapies.
The revisions are especially beneficial to the CD19 lymphoma CAR-T meds because their market penetration has remained stagnant at about 20% for some time, the Leerink analysts noted.
The removal of the REMS programs in their entirety follows an FDA decision last year to eliminate requirements for educational and training materials, as well as a mandate to report adverse events suggestive of CRS or neurological toxicities, specifically under REMS.
The move represents a positive sign of some regulatory continuity at the FDA’s cell and gene therapy department since the installment of several new leaders, including the new Center for Biologics Evaluation and Research (CBER) director, Vinay Prasad, M.D., and the reported sudden ouster of Nicole Verdun, M.D., director of the Office of Therapeutic Products within CBER last week.
While the REMS items are gone, the CAR-T products’ labels still carry black box warnings about CRS, neurotoxicity and secondary T-cell malignancies. During an interview last fall, then-CBER Director Peter Marks, M.D., Ph.D., told Fierce that the agency was reevaluating the classwide secondary cancer warnings that were recently slapped on CAR-T therapies’ labels.