FDA expands TOFIDENCE (tocilizumab-bavi) indications to include CAR T-cell–induced CRS and pediatric COVID-19

Clinicians managing the toxicities of chimeric antigen receptor (CAR) T-cell therapy now have an additional biosimilar option available after the FDA approved expanded indications for tocilizumab-bavi (TOFIDENCE; Organon), a biosimilar referencing intravenous tocilizumab (ACTEMRA; Chugai/Genentech). The supplemental Biologics License Application (sBLA) approval covers treatment of adults and pediatric patients aged 2 years and older with CAR T-cell–induced severe or life-threatening cytokine release syndrome (CRS), as well as hospitalized adult and pediatric patients aged 2 years and older with coronavirus disease 2019 (COVID-19) who require systemic corticosteroids and supplemental respiratory support.¹

"The approval of these new indications for TOFIDENCE is a vital step forward in expanding access to treatment options that address critical needs, including for patients facing CRS, a serious side effect of CAR-T therapies," said Jon Martin, US Commercial Lead, Biosimilars and Established Brands at Organon. He added that biosimilar adoption may help reduce the affordability burden of high-cost reference biologics on the health care system.¹

Clinical context: CRS burden and the role of IL-6 inhibition in CAR-T management

CRS is among the most clinically significant complications of CAR T-cell therapy, occurring across a broad range of cellular immunotherapy products. Clinical trial data indicate that CRS rates associated with CAR T-cell therapy range from approximately 50% to 90%, with severe cases capable of progressing to hemodynamic instability and multi-organ dysfunction.² Real-world data from the National Inpatient Sample further underscore this burden, documenting meaningful hospitalization costs, prolonged length of stay, and elevated in-hospital mortality among patients who develop CRS.²

IL-6 receptor antagonism is a mainstay of CRS management, endorsed by major oncology societies as standard of care for severe or life-threatening cases.³ Tocilizumab, the reference product, has been used in this setting since its initial FDA approval for CAR T-cell–induced CRS in 2017. The availability of biosimilar alternatives in this space carries potential downstream implications for treatment access and institutional drug costs, particularly as CAR T-cell therapy use continues to expand across hematologic malignancies and, increasingly, solid tumors.

Regulatory basis for TOFIDENCE approval in CRS and COVID-19

The expanded indications for tocilizumab-bavi were supported by a totality-of-evidence approach consistent with the FDA's regulatory framework for biosimilar approval, rather than dedicated CRS- or COVID-19–specific efficacy trials.¹ Biosimilarity was established through a comprehensive data package that included a global phase 3 clinical trial in patients with moderate-to-severe rheumatoid arthritis (RA) evaluating pharmacokinetics, efficacy, immunogenicity, and safety of tocilizumab-bavi versus reference tocilizumab.⁴

Indication extrapolation, in which biosimilarity data from one condition supports labeling across all approved indications of the reference product, is a well-established regulatory mechanism under FDA guidance and was the pathway applied here.¹ This approval aligns tocilizumab-bavi's label with the full scope of intravenous reference tocilizumab indications.

For COVID-19, the approved population consists of hospitalized adults and children aged 2 years and older who are receiving systemic corticosteroids and require supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).¹

Drug background: tocilizumab-bavi mechanism and existing indications

Tocilizumab-bavi is a recombinant humanized monoclonal antibody that acts as an interleukin-6 (IL-6) receptor antagonist, inhibiting both membrane-bound and soluble IL-6 receptor signaling.¹ IL-6 is a pleiotropic cytokine central to the inflammatory cascade implicated in RA, autoinflammatory conditions, and the hyperinflammatory states associated with CRS and severe COVID-19.

TOFIDENCE was the first tocilizumab biosimilar approved in the US market, receiving initial FDA clearance in September 2023 and commercially launching in May 2024.⁴ Organon acquired US regulatory and commercial rights to the product from original developer Bio-Thera Solutions Ltd. in 2025.¹ Prior to this sBLA approval, the drug was indicated for moderately to severely active RA in adults, giant cell arteritis (GCA) in adults, polyarticular juvenile idiopathic arthritis (PJIA) in patients aged 2 years and older, and systemic juvenile idiopathic arthritis (SJIA) in patients aged 2 years and older.⁴

Safety profile and clinical considerations

The safety profile of tocilizumab-bavi is consistent with the established class profile of IL-6 inhibitors. The most common adverse reactions with intravenous tocilizumab (incidence ≥5%) include upper respiratory tract infection, nasopharyngitis, headache, hypertension, and elevated alanine aminotransferase (ALT).¹ The product carries a boxed warning for serious infections, including tuberculosis, invasive fungal infections, bacterial and viral pathogens, and other opportunistic organisms, any of which may lead to hospitalization or death.¹

Prescribers should test patients for latent tuberculosis before initiation (this requirement is specifically waived for the COVID-19 indication), and TOFIDENCE should not be administered in patients with active infection. Serious cases of hepatic injury, some resulting in liver transplant or death, have been reported with intravenous tocilizumab products; liver function monitoring is required. Drug interactions affecting cytochrome P450 3A4 substrates, including oral contraceptives and certain statins, should also be considered, as IL-6 inhibition may restore CYP450 activity and increase metabolism of these agents.¹

Open questions and next steps

While the indication extrapolation pathway for biosimilar approval is scientifically defensible, clinicians may note the absence of tocilizumab-bavi–specific efficacy data in CRS or COVID-19 populations. The regulatory framework provides reasonable confidence in pharmacological equivalence, but health system formulary decisions and institutional switching policies will likely shape real-world uptake. As CAR T-cell therapy expands into earlier lines of treatment and new disease categories, demand for cost-effective management of CRS toxicities is expected to grow, reinforcing the clinical relevance of biosimilar availability in this space.

References

1. Organon. Organon secures US FDA approval expanding indications for TOFIDENCE® (tocilizumab-bavi) in cytokine release syndrome (CRS) and pediatric COVID-19. Press release. June 10, 2026. Accessed June 10, 2026. https://organon2021tf.q4web.com/news/news-details/2026/Organon-Secures-US-Food-and-Drug-Administration-Approval-Expanding-Indications-for-TOFIDENCE-tocilizumab-bavi-in-Cytokine-Release-Syndrome-CRS-and-Pediatric-COVID-19/default.aspx

2. Synnott P, et al. Cytokine release syndrome in solid tumors. Cancer. 2025. doi:10.1002/cncr.70069

3. Shah A, Pyatetsky I, Thompson B, Chen C, Chang V. Clinical burden and predictors of cytokine release syndrome in CAR-T cell therapy for hematologic malignancies: Insights from a national cohort. Blood. 2025;146(Suppl 1):2393. doi:10.1182/blood-2025-2393

4. US Food and Drug Administration. FDA approves first biosimilar to Actemra to treat adult and pediatric arthritis. Published September 29, 2023. Accessed June 10, 2026. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-first-biosimilar-actemra-treat-adult-and-pediatric-arthritis