FDA Expands Approval for Tocilizumab Biosimilar to Treat CRS

The US FDA has approved an expanded indication for the intravenous (IV) formulation of tocilizumab-anoh (Avtozma), a biosimilar to tocilizumab (Actemra), to include the treatment of cytokine release syndrome (CRS) in adults and pediatric patients aged 2 years and older.¹ This approval brings the biosimilar's IV formulation to full indication alignment with the reference product in the US, a significant milestone in expanding therapeutic options for a potentially life-threatening condition.

CRS is an acute, systemic inflammatory response often triggered by immune-modulating therapies such as CAR T-cell therapy. The condition, sometimes referred to as a "cytokine storm," results from the rapid and excessive release of proinflammatory cytokines into the bloodstream. This can lead to widespread inflammation and organ damage, with clinical manifestations ranging from mild, flu-like symptoms to severe complications like hypotension, respiratory distress, and multi-organ failure.

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

The mechanism of action for tocilizumab-anoh is its role as a humanized monoclonal antibody that functions as an interleukin-6 (IL-6) receptor antagonist. IL-6 is a key proinflammatory cytokine that plays a central role in driving the pathological immune activation seen in CRS. By binding to both membrane-bound and soluble IL-6 receptors, tocilizumab-anoh effectively blocks IL-6 signaling, thereby mitigating the severe inflammatory cascade and its associated systemic toxicities. This targeted approach aims to dampen the immune system's overreaction without compromising the primary therapeutic effects of the underlying immunotherapy, which is a critical consideration in CAR T-cell therapy.

The FDA's decision to expand the indication for tocilizumab-anoh was based on a comprehensive data package demonstrating biosimilarity to the reference product. This included a global phase 3 clinical trial that evaluated the efficacy, pharmacokinetics, safety, and immunogenicity of tocilizumab-anoh compared to the reference drug in patients with moderate to severe rheumatoid arthritis (RA). The data from this trial, which formed the basis for the biosimilar's initial approvals in RA, giant cell arteritis, polyarticular juvenile idiopathic arthritis, systemic juvenile idiopathic arthritis, and COVID-19 earlier this year, supported the expanded indication.²

The approval for this expanded indication is particularly relevant to the oncology community, where the use of CAR T-cell therapy is increasing.¹ As a standard of care for severe or life-threatening CAR T-cell–induced CRS, the availability of a biosimilar provides an additional, and potentially more cost-effective, treatment option.

The IV formulation of tocilizumab-anoh is expected to be available in the US on August 31, 2025, following a patent settlement agreement with Genentech. The availability of this biosimilar is expected to increase market competition, potentially leading to reduced healthcare costs for institutions and patients.

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 7, 2025. https://tinyurl.com/22j9r42h

2. U.S. FDA approves Celltrion's AVTOZMA® (tocilizumab-anoh), a biosimilar to ACTEMRA®. News release. Celltrion Inc. January 31, 2025. Accessed August 7, 2025. https://tinyurl.com/3fyjkp24