Genentech's tocilizumab shortage due to Covid-19 now hits CAR-T recipients, with FDA offering alternatives to help
Soon after San Francisco-based Genentech won an EUA for tocilizumab as a treatment for hospitalized Covid patients last summer, the company announced a shortage of the drug while pointing to the emergence of the Delta variant and the slowing of vaccination rates across the US.
“This new wave of the pandemic has led to Genentech experiencing an unprecedented demand for Actemra IV– well-over 400% of pre-COVID levels over the last two weeks alone and it continues to increase,” the company said in August.
More recently, the shortage is causing issues for others who might need tocilizumab following the infusion of CAR-T cell immunotherapies as cancer treatments, due to the potential for severe or even life-threatening cytokine release syndrome.
All CAR-Ts are subject to risk evaluation and mitigation strategies (REMS) OKed by the FDA, which in this case require that prior to CAR-T infusions, a minimum of two doses of tocilizumab are available on-site for each patient and are ready for immediate administration (within 2 hours) due to the potential for CRS.
The worldwide shortage of tocilizumab means the FDA has to get flexible with its requirement that two doses be on site, and the agency issued new guidance on Friday explaining how.
For CAR T cell immunotherapies subject to these REMS, the FDA says it does not intend to object if health care providers prescribe, dispense, or administer these biologics when two doses of tocilizumab are not available, provided that all of the following circumstances are accounted for:
- Before infusion of the CAR-T immunotherapy to a patient, one dose of tocilizumab is available on-site for each patient for immediate administration (within 2 hours), and there is access to an additional dose of tocilizumab within 8 hours after each previous dose, if needed.
- Health care providers use their best medical judgment in weighing the benefits and risks of treatment with the CAR T cells in the context of the shortage. “There are limited data to support the use of alternative agents directed against interleukin (IL)-6 or other cytokines for CRS management in general, and in particular, as first-line therapy,” FDA notes.
- Health care providers communicate with their patients regarding their decision-making, including the risks and benefits of treatment with CAR T cell immunotherapy in the context of the tocilizumab shortage, and the potential challenges in the treatment of CRS and potential use of alternative CRS management approaches.
Under the REMS, certified hospitals and their associated clinics also should maintain adequate records of patient-level data regarding the use of CAR T cell immunotherapies and must document and report any serious adverse events suggestive of CRS or neurological toxicity, the FDA says.
Genentech also must maintain records of certified hospitals and their associated clinics that were not able to comply with REMS requirements and instead provide CAR T cell immunotherapy in a manner consistent with this policy due to the tocilizumab shortage.
“Although all REMS requirements remain in effect during this time, FDA does not intend to take enforcement action against sponsors or others with respect to the REMS requirements relating to the access to tocilizumab” during this shortage, the agency adds.