FDA Approves Tocilizumab Biosimilar for CAR T-Cell Therapy–Induced CRS

The FDA has approved the intravenous (IV) formulation of tocilizumab-anoh (Avtozma), a biosimilar referencing IV tocilizumab (Actemra) for the treatment of patients at least 2 years of age with chimeric antigen receptor (CAR) T-cell therapy–induced severe or life-threatening cytokine release syndrome (CRS).1

Previously, in January 2025, the FDA approved the IV infusion of tocilizumab-anoh for the treatment of patients with inflammatory diseases, including rheumatoid arthritis, giant cell arteritis, polyarticular juvenile idiopathic arthritis, systemic juvenile idiopathic arthritis, and COVID-19. The indications for the IV formulation of tocilizumab-anoh now align with all FDA-approved indications for IV tocilizumab.

“We are proud that IV [tocilizumab-anoh] has now achieved full indication alignment with the reference IV [tocilizumab]. This milestone marks an important step forward in our mission to deliver a safe and effective therapy for CRS,” Thomas Nusbickel, chief commercial officer at Celltrion USA, stated in a news release.1 “This FDA approval expands access to high-quality biologics and supports beneficial patient outcomes across multiple therapeutic areas.”

Tocilizumab-anoh contains the active ingredient tocilizumab and is a recombinant interleukin-6 receptor–directed human monoclonal antibody. The recommended IV dosage for patients with CRS is 60-minute infusions at 12 mg/kg in patients weighing less than 30 kg and 8 mg/kg in those weighing at least 30 kg.2 In the CRS population, tocilizumab-anoh can be given alone or in combination with corticosteroids. In patients with CRS—as well as those with rheumatoid arthritis and COVID-19—tocilizumab-anoh doses exceeding 800 mg per infusion are not recommended. Notably, if clinical improvement in the signs and symptoms of CRS is not observed after the first dose of tocilizumab-anoh, a maximum of 3 additional doses of the agent may be given. Consecutive doses should be administered at least 8 hours apart.

Patients are required to undergo baseline complete blood count and liver function tests prior to treatment with tocilizumab-anoh. According to the tocilizumab-anoh prescribing information, patients with severe or life-threatening CRS often present with cytopenias or elevated alanine aminotransferase/aspartate aminotransferase levels due to lymphodepleting chemotherapy or the CRS itself.2 Therefore, the decision to treat patients with tocilizumab-anoh should weigh the potential benefits of CRS management with the risks associated with short-term tocilizumab-anoh treatment.

A retrospective pooled analysis of data from several clinical trials evaluated 45 patients with severe or life-threatening CAR T-cell therapy–induced CRS who received IV tocilizumab at the recommended dose with or without high-dose corticosteroids. The median time from the start of CRS to the first dose of tocilizumab was 4 days (range, 0-18), and patients received a median of 1 (range, 1-4) dose of tocilizumab.

Tocilizumab response was defined as CRS resolution (lack of fever and vasopressor independence for at least 24 hours) within 14 days of the first dose of tocilizumab if the patient required no more than 2 doses of tocilizumab and received no drugs other than tocilizumab and corticosteroids for the management of CRS. Overall, 69% of patients (95% CI, 53%-82%) responded to tocilizumab. Investigators did not observe adverse effects related to tocilizumab.

Among the patients studied in the analysis were 25 children aged 2 to 12 years and 17 adolescents aged 13 to 18 years. Notably, investigators saw no safety or efficacy differences with tocilizumab use between the pediatric and adult patient populations. However, the clinical studies included in the analysis did not enroll sufficient numbers of patients at least 65 years old to demonstrate whether this age group responds differently from younger patients.

The IV formulation of tocilizumab-anoh is expected to be available in the US August 31, 2025.1

References

1. FDA approves expanded indication for Avtozma (tocilizumab-anoh) intravenous (IV) formulation in cytokine release syndrome (CRS). News release. Celltrion, Inc. August 6, 2025. Accessed August 6, 2025. https://www.prnewswire.com/news-releases/fda-approves-expanded-indication-for-avtozma-tocilizumab-anoh-intravenous-iv-formulation-in-cytokine-release-syndrome-crs-302522996.html
2. Avtozma. Prescribing information. Celltrion; 2025. Accessed August 6, 2025. https://www.celltrion.com/ko-kr/comm/surl/107