The Food and Drug Administration (FDA) has issued temporary guidance with respect to certain risk evaluation and mitigation strategy (REMS) requirements for chimeric antigen receptor (CAR) T-cell immunotherapies due to an ongoing shortage of tocilizumab related to the COVID-19 pandemic.
Tocilizumab is an interleukin-6 (IL-6) antagonist that is FDA-approved for the treatment of CAR T cell-induced severe or life-threatening cytokine release syndrome (CRS) in adults and pediatric patients 2 years of age and older. The REMS for CAR T-cell immunotherapies requires that health care facilities ensure that a minimum of 2 doses of tocilizumab are available for each patient for administration within 2 hours after infusion, if needed for the treatment of CRS.
In June 2021, the FDA issued an Emergency Use Authorization (EUA) for tocilizumab for use in the treatment of COVID-19 in hospitalized adults and pediatric patients who are receiving systemic corticosteroids and require supplemental oxygen, noninvasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation. Shortly after, Genentech announced that tocilizumab (marketed under the brand name Actemra) was in shortage.
The Company issued a follow-up statement on December 6, 2021 indicating that the product continues to be in high demand and that the “availability of Actemra SC and IV formulations continues to vary over time.”
To mitigate concerns over the shortage as it relates to the REMS requirements for CAR T-cell immunotherapies, the Agency has issued a temporary policy for when it may not be feasible to have 2 doses of tocilizumab on-site.
Specifically, the FDA would not object if 2 doses are unavailable if before infusion of the CAR T-cell immunotherapy, 1 dose of tocilizumab is available on-site for each patient for immediate administration (within 2 hours). There should also be access to an additional dose of tocilizumab within 8 hours after each previous dose of tocilizumab administered to each patient, if needed. Patients should also be informed about the risks and benefits of treatment with CAR T-cell immunotherapy in the context of the tocilizumab shortage.
Though data are limited, health care providers may consider alternative agents inhibiting activities of IL-6 or other cytokines in managing CAR T-cell immunotherapy-induced CRS. Potential challenges in the treatment of CRS related to the tocilizumab shortage and use of alternative CRS management approaches should be discussed with patients.
Additional recommendations related to the temporary policy can be found here.
The tocilizumab shortage also impacts patients treated for other FDA-approved conditions including rheumatoid arthritis, giant cell arteritis, systemic sclerosis-associated interstitial lung disease, polyarticular juvenile idiopathic arthritis, and systemic juvenile idiopathic arthritis.
Policy for certain REMS requirements during the tocilizumab shortage related to the COVID-19 public health emergency. Accessed December 13, 2021. https://www.fda.gov/media/154771/download.