COVID-19-driven shortage of tocilizumab may impact delivery of CAR T-cell therapy
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The FDA has included tocilizumab among its list of drugs currently in shortage.
In addition to being used primarily to treat certain types of rheumatoid and juvenile arthritis, tocilizumab (Actemra, Genentech/Roche) serves as treatment for COVID-19-related cytokine release syndrome, which has made it difficult for some providers to obtain doses, according to the agent’s manufacturer.
“The unprecedented surge in worldwide demand and supply constraints driven by delta variant spikes in much of the rest of the world that preceded the current situation in the U.S. have led to a global shortage of Actemra supply for at least the next several weeks,” a Genentech spokesperson told Healio.
“We expect to receive scheduled replenishments by the end of August,” the spokesperson added. “However, if the pandemic continues to spread at its current pace, we anticipate additional periods of stockout in the weeks and months ahead.”
The FDA in June approved tocilizumab, an interleukin-6 receptor antagonist, for emergency use by certain hospitalized patients with severe COVID-19 symptoms — typically those who require respiratory intervention. This in tandem with the tepid enthusiasm for COVID-19 vaccination in certain areas has heightened concerns about the impact of potential periodic spikes in tocilizumab demand on clinics that provide CAR T-cell therapies.
CAR-T providers may “need to get creative” to deal with this and future shortages, according to Frederick L. Locke, MD, co-leader of the immune-oncology program and vice chair of the department of blood and marrow transplant and cellular immunotherapy at Moffitt Cancer Center.
Locke — who also serves as a member of the Cell Therapy Next Peer Perspective Board — said this shortage is unique for cell therapy clinics because of the FDA’s Risk Evaluation and Mitigation Strategies (REMS) requirement that two doses of tocilizumab be available before infusion for each patient who undergoes CAR T-cell therapy.
“It risks us having to cancel CAR-T treatments or delay them,” he told Healio. “We have contracted with the manufacturers to comply with the REMS requirements, which is — in turn — an agreement between the manufacturers and the FDA. This requires us to have tocilizumab on hand.”
If needed, patients receive tocilizumab at the onset of CRS, which typically begins within a week after CAR-T infusion, according to Locke. A supply shortage, therefore, poses significant issues for a cell therapy clinic like his, where approximately 40% of patients who receive commercial CAR-T will receive at least one dose of tocilizumab.
Short-term response
Some of the initial guidance from the manufacturer and distributors of tocilizumab has been fuzzy, according to Locke.
For its part, Genentech said it is aware of the unique concerns of patients awaiting CAR T-cell therapy during a time or shortage.
“We are working urgently on solutions to minimize the impact for them,” the Genentech spokesperson told Healio. “As replenishments become available in the U.S, we will be moving forward with distribution strategies that we believe are the fastest and most direct way to distribute the medicine to patients with the highest medical need and those who have few or no other treatment options available during the pandemic.”
The spokesperson recommended clinics that provide therapies such as CAR-T contact their distributor for questions regarding order requests.
Clinicians should be proactive in the face of such an important drug shortage, Locke said. He agreed clinics should start a dialogue, but on a local level first with their center’s pharmacy department. He suggested having them reach out to the manufacturer via distributors to explain why the drug is being ordered and its importance to the patient and procedure.
Long-term solutions
Making predictions about future need and supply of tocilizumab is uncertain at best in this environment, Locke said.
Because Genentech has cautioned customers about factors that could influence future supplies, Locke said CAR-T providers should prepare for long-term periodic shortages of the drug.
“Centers will need to switch to a more proactive model,” he said. “Rather than stocking the drug on an as-needed basis, they will need to project outward and — based on the shelf life of the drug — keep enough on the shelf to meet their needs.”
Locke also suggested clinics devise a strategy for alternative anti-CRS agents and ensure they are readily available at their center and can be ordered up as needed in case of a shortage.
Although it is impossible to predict the trajectory of COVID-19 or its variants, Locke said shortages of tocilizumab could be a recurring issue — especially at a local level.
He said centers in areas where vaccination rates are low should prepare for a shortage and, if vaccination rates remain low, expect periodic repeats when infection rates spike.
“They will want to use tocilizumab for severe COVID patients,” Locke said. “I expect the issue to continue until production of the drug changes or more people in the U.S. are vaccinated.”
References:
FDA. Coronavirus (COVID-19) update: FDA authorizes drug for treatment of COVID-19. June 24, 2021. Available at: www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-drug-treatment-covid-19. Accessed Aug. 27, 2021.
FDA. FDA drug shortages. Revised Aug. 20, 2021. Available at: www.accessdata.fda.gov/scripts/drugshortages/dsp_ActiveIngredientDetails.cfm?AI=Tocilizumab%20Injection&st=c. Accessed Aug 27, 2021.
For more information:
Frederick L. Locke, MD, can be reached at frederick.locke@moffitt.org.
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