FDA Approves Expanded Indication to Tocilizumab-Anoh IV for CRS

The FDA has approved the expanded indication of the intravenous (IV) formulation of tocilizumab-anoh (Avtozma; Celltrion Inc) to include treatment of cytokine release syndrome (CRS) in adult and pediatric patients aged 2 years and older. Tocilizumab-anoh IV is now approved for all the same conditions as Actemra IV (tocilizumab; Roche, Genentech) in the US. Earlier this year, tocilizumab-anoh was initially approved as a biosimilar to Actemra for the treatment of rheumatoid arthritis (RA), giant cell arteritis, polyarticular juvenile idiopathic arthritis, systemic juvenile idiopathic arthritis, and COVID-19.^1,2

Blood sample for Cytokine test, used to pathophysiology of immune, infectious, or inflammatory disorders. Cytokine Release Syndrome - Image credit: MdBabul | stock.adobe.com

"We are proud that [tocilizumab-anoh] 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," Thomas Nusbickel, chief commercial officer at Celltrion USA, said in a news release.¹

Cytokine Release Syndrome

CRS is caused when the immune system responds to infection or immunotherapy drugs more aggressively than it should, leading to the excessive release of cytokines into the bloodstream. Once the chemicals are released, individuals can experience symptoms of fever, nausea, fatigue, and body aches, which could range from mild and flu-like to severe and life-threatening. However, symptoms can vary depending on what body systems are impacted by CRS.³

While treatment for CRS may vary, common therapies include IV fluids, drugs to reduce fever, oxygen, mechanical ventilation, blood transfusions, dialysis, electrolyte management, and heart medications. Typically, individuals that develop CRS from immunotherapy, such as CAR T-cell therapy, recover in about 1 to 2 weeks, but this depends on the severity.³

Tocilizumab-Anoh Indications

As a recombinant humanized monoclonal antibody, tocilizumab-anoh works by blocking the IL-6 receptor. The approval was based on data from a phase 3 clinical trial that evaluated the biosimilar's efficacy, pharmacokinetics, safety, and immunogenicity when compared to the reference, Actemra, when coadministered with methotrexate for patients with moderate to severe active RA.^1,2

Individuals with RA who were aged 18 to 75 years old were included in the study and randomly assigned on day 1 to receive either the biosimilar or the European Union formulation of the reference product every 4 weeks until week 20. Following, individuals on the biosimilar continued with the same treatment every 4 weeks until week 48. Individuals who were on the reference product were then reassigned to either continue with the reference product or switch to the biosimilar every 3 weeks until week 48.²

The primary goals of the study were to measure the mean change from the baseline in the Disease Activity Score-28 for RA with ESR (DAS28-ESR) at both week 12 and week 24. Other outcomes that were measured included changes from baseline in ESR, CRP, Simplified Disease Activity Index, and Clinical Disease Activity.²

Of the 471 patients in the first treatment period, 234 received the biosimilar and 237 received the reference product, with 9 biosimilar patients and 18 reference product patients discontinuing. In the second period, 444 patients continued, with 225 staying on the biosimilar, 109 remaining on the reference product, and 110 switching from the reference product to its biosimilar. There were 8, 3, and 2 treatment discontinuations in these respective groups. The results demonstrated that the study met its primary end point for DAS28-ESR change at weeks 12 and 24, with the biosimilar and the reference product showing similar improvements across all secondary outcomes.²

With the expanded indications, the biosimilar now has similar indications to the reference product, providing treatment for CRS and various inflammatory conditions.¹

"This FDA approval expands access to high-quality biologics and supports beneficial patient outcomes across multiple therapeutic areas,” Nusbickel said in the news release.¹

REFERENCES

1. FDA approves expanded indication for AVTOZMA® (tocilizumab-anoh) intravenous (IV) formulation in cytokine release syndrome (CRS). Celltrion. News release. 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. Gallagher A. FDA Approves Tocilizumab-Anoh as a Biosimilar to Actemra. Pharmacy Times. January 31, 2025. Accessed August 6, 2025. https://www.pharmacytimes.com/view/fda-approves-tocilizumab-anoh-as-a-biosimilar-to-actemra

3. Cytokine Release Syndrome (CRS). Cleveland Clinic. News release. Updated April 7, 2022. Accessed August 6, 2025. https://my.clevelandclinic.org/health/diseases/22700-cytokine-release-syndrome