By Gina Shaw
Originally published by Pharmacy Practice News and Specialty Pharmacy Continuum
As of June 26, 2025, the FDA has removed certain Risk Evaluation and Mitigation Strategy (REMS) requirements from all but one of the currently approved B-cell maturation antigen (BCMA)- and CD19-directed autologous chimeric antigen receptor T-cell (CAR-T) immunotherapies.
FDA officials said the decision on CAR-T products reflects growing real-world experience with these treatments and evolving safety data. The REMS removal also “expedites the delivery of potentially curative treatments to patients and reduces burden on providers,” Vinay Prasad, MD, MPH, the former chief medical and scientific officer and former director of the Center for Biologics Evaluation and Research at the FDA, said in a statement.
The decision applies to six currently approved CAR-Ts (box), with the safety program still intact for the anti-CD19 CAR-T therapy obecabtagene autoleucel (Aucatzyl, Autolus), which was approved by the FDA in early November 2024 for the treatment of adults with acute lymphoblastic leukemia.
Building on Earlier Actions
The move by the FDA follows previous decisions on other complex care medications, noted Simone Ndujiuba, PharmD, BCOP, a clinical oncology pharmacist for Prime Therapeutics. “Over the years, the FDA has removed drugs from the REMS program when it determines the benefit outweighs the risk,” Dr. Ndujiuba noted, citing as examples ponatinib (Iclusig, Takeda) and emtricitabine and tenofovir disoproxil fumarate (Truvada, Gilead) and its generics. “REMS removal does not change a drug’s adverse events profile. So close monitoring after CAR-T administration is still required,” she said.
The elimination of REMS means institutions providing these therapies are not required to have immediate on-site access to tocilizumab (Actemra, Genentech), which is needed to manage cytokine release syndrome, a potentially life-threatening adverse reaction to CAR-T therapy. Sites of care also are no longer required to maintain REMS-mandated certification. The REMS removal also cuts down on posttreatment monitoring guidelines, with patients tracked daily for about one week followed by continued monitoring through two weeks postinfusion (down from four). In another change, patients are now required to stay near the treatment center for two weeks (down from four) and advised to avoid driving for two weeks (down from eight).
But other requirements will continue. “[Boxed] warnings remain, and centers still need to demonstrate competency and adherence to best practices in cellular therapy to ensure patient safety,” Dr. Ndujiuba said. She added that manufacturers still need to conduct post marketing safety studies to assess the risk of secondary malignancies and long-term safety for 15 years after REMS administration, per FDA regulations. Moreover, the agency will stay the course with its continuous monitoring and assessment of safety adverse event reporting requirements for the drug class.
Without the more extensive REMS mandates, institutions may find it easier to onboard these therapies because personnel and administrative resource costs could decrease, noted Jakob Reiser, PhD, the senior director of regulatory affairs at Vector BioMed, which develops and manufactures lentiviral vectors for cell and gene therapies. The burden on patients will also diminish, Dr. Reiser noted. “If you’re required to be in close proximity to the clinical facility for an extended period, that significantly adds to your cost of care,” he explained.
Dr. Reiser said the removal of the CAR-T REMS is based on solid science. “There is now a rich body of information, both clinical and otherwise, regarding these specific therapies,” he said. “Kymriah and Yescarta were approved in 2017, followed by the other anti-CD19 CAR-Ts and the anti-BCMAs. Many thousands of patients have been treated with these CAR-T products without serious adverse events.”
Opening the Doors to More Hospitals
Large academic centers will likely continue to dominate CAR-T delivery in the near term, given the complexity of the treatment, coordinating with manufacturers and management of toxicities. But institutions that were previously deterred by REMS complexities, such as regional cancer centers with existing hematology/ oncology infrastructure and community hospitals with transplant units or strong critical care teams, may now consider entering the CAR-T space, Dr. Ndujiuba noted. “As more centers move forward with CAR-T administration, it raises the question of supply during increased demand,” she said. “For some time, there was a backlog of patients cleared for CAR-T [therapy], but due to manufacturing challenges, the supply sometimes could not meet the demand.”
Additional questions are also raised by the REMS removal. “Is manufacturer certification alone enough for an institution to deliver these therapies, or should Foundation for the Accreditation of Cellular Therapy [FACT] accreditation be required to ensure safe practice?” Dr. Ndujiuba asked. Another key question, she noted, is whether the potential creation and release later this year of a FACT community-based standard for CAR-T therapy will provide the best practices needed to allow more community sites to safely begin administration.
And then there is the question of cost. Multiple manufacturers and other stakeholders are working to improve the affordability, scalability and global accessibility of CAR-T therapies, including investment in allogeneic (“off-the-shelf”) products that could eliminate the expensive and burdensome apheresis step.
To that end, Vector BioMed and its original parent company, the nonprofit biotechnology organization Caring Cross, are working to develop point-of-care manufacturing platforms for CAR-T and other cell therapies and share them with partner hospitals and research centers in low-resource settings, reducing cost and logistical hurdles. “The goal is to convert these patient T cells into CAR T cells without having to rely on costly, technically demanding equipment,” Dr. Reiser explained. “Rather than having only a handful of central facilities where those patient-derived T cells are shipped and then transduced and tested for release and shipped back to a clinic where the cells are administered, that ideally will happen in a more distributed, geographically accessible way closer to where the patients live. There are so many CAR-T therapies in the pipeline that will ultimately be licensed, and it is essential that we keep that cost balance in check.”
As efforts to increase access continue, safety must remain paramount, Dr. Ndujiuba noted. “With the initial FDA approvals for the treatment of blood cancers, the approvals in solid tumor, and the anticipated use in noncancer indications, CAR-T use will continue to grow,” she said. “Now that REMS requirements have ended, continued dedication to safety and therapy optimization is vital to patient care.”
The sources reported no relevant financial disclosures.