FDA Updates REMS for CAR T-Cell Therapies

Because of a COVID-19 related shortage, facilities may not have immediate access to Actemra, which is required as part of the REMS programs for CAR T-cell therapies.

The FDA is issuing a temporary policy on the risk evaluation and mitigation strategies (REMS) requirements related to CAR T-cell therapies because of a shortage of Genentech’s Actemra (tocilizumab) related to the COVID-19 public health emergency.

The shortage was a result of increased demand and supply issues after Actemra received an emergency use authorization (EUA) in June 2021 allowing Actemra to be used for hospitalized adults and pediatric patients 2 years of age and older who are receiving systemic corticosteroids and require supplemental oxygen. Actemra is a humanized interleukin-6 (IL-6) receptor antagonist that is also approved to treat patients with rheumatoid arthritis, as well as for use with adults and pediatric patients (2 years of age and older) who develop CAR T cell-induced cytokine release syndrome.

Several CAR T-cell therapies have been approved, including Kymriah (tisagenlecleucel), Yescarta (axicabtagene ciloleucel), Tecartus (brexucabtagene autoleucel), Breyanzi (lisocabtagene maraleucel), and Abecma (idecabtagene vicleucel). These therapies, which treat patients with certain kinds of lymphomas and leukemias and multiple myeloma, are associated with cytokine release syndrome.

The FDA requires in its REMS for CAR T-cell therapies that a minimum of two doses of Actemra are available on-site for each patient and are ready for immediate administration (within two hours) for patients who experience the life-threatening adverse event.

The regulatory agency said in its recent policy statement that it recognizes this may not be feasible because of the shortage of Actemra. Agency officials said they would allow one dose to be available at the time of administration of the CAR T-cell therapy, as long as the facility had access to an addition dose that could be given at eight hours.

The FDA advised providers to weigh risks and benefits of using alternatives to Actemra, saying this is limited data to support the use of other interleukin (IL)-6 inhibitors or other cytokines in managing CRS in patients who have received CAR T-cell therapy.

Related: Hospital Pharmacists Concerned About Actemra Shortage

In August 2021, Genentech indicated there was a shortage of Actemra due to the COVID-19 pandemic, and in early December said that the availability of the monoclonal antibody continues to vary.