FDA Seeks Additional Information on Subcutaneous Anifrolumab BLA

The FDA has issued a complete response letter (CRL) for AstraZeneca’s Biologics License Application (BLA) seeking approval of a subcutaneous formulation of anifrolumab for the treatment of adults with systemic lupus erythematosus (SLE).

What Does A Complete Response Letter Mean for a Company?

A CRL indicates that the FDA has completed its review of an application but is requesting additional information before it can approve the product. While receiving a CRL can delay a potential approval timeline, it does not necessarily indicate problems with a therapy’s effectiveness or safety. Requests may relate to factors such as data presentation, manufacturing, labeling or product administration. Sponsors can address the agency’s requests and resubmit their application for further review.

Recent CRLs across therapeutic areas reflect the varied and often product-specific considerations involved in regulatory review. For example, in January 2026, the FDA issued a CRL to Aquestive Therapeutics for its sublingual epinephrine film, citing deficiencies related to human factors, packaging and administration rather than underlying clinical efficacy or safety. The company said it plans to address the issues and resubmit the application later this year.

What Does the AstraZeneca CRL Entail?

According to the company, the CRL detailed additional information that the FDA requested as part of its review. AstraZeneca said it has provided the requested materials and is working with the FDA to advance the application. A regulatory decision on the updated submission is expected in the first half of 2026. The intravenous formulation of anifrolumab remains commercially available in the US.

What Was the BLA Supported By?

The BLA was supported by results from the Phase III TULIP-SC trial, which evaluated a self-administered subcutaneous formulation of anifrolumab in adults with moderately to severely active, autoantibody-positive SLE. Participants in both arms of the study received standard therapy, which could include oral corticosteroids, antimalarials and/or immunosuppressants.

A pre-specified interim analysis showed that the TULIP-SC study met its primary endpoint, demonstrating a statistically significant reduction in disease activity compared with placebo at Week 52. Disease activity was assessed using the British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA), a composite measure that requires improvement across all affected organ systems without new disease flares.

The safety profile observed in the trial was reported to be consistent with the known clinical profile of the intravenous formulation.

TULIP-SC is a randomized, double-blind, placebo-controlled Phase III study in adults with SLE that evaluated once-weekly subcutaneous anifrolumab versus placebo. A planned interim analysis was conducted at Week 52, and the study includes an open-label extension for participants who completed treatment.

In December 2025, the European Union (EU) approved subcutaneous anifrolumab for adult patients with moderate to severe SLE.

Challenges in SLE Drug Development

Difficulties in demonstrating consistent treatment benefit have been observed across multiple SLE development programs. In 2025, Merck KGaA reported that its oral lupus candidate enpatoran did not meet the primary endpoint in the SLE cohort of its Phase II WILLOW study. This was based on disease activity assessments using a composite measure, despite higher response rates observed in some patient subgroups. 

What Is Anifrolumab?

Anifrolumab is a fully human monoclonal antibody that targets the type I interferon receptor, blocking signaling pathways involved in immune activation and inflammation. Type I interferons are believed to play a central role in the pathophysiology of SLE, a chronic autoimmune disease that can affect multiple organ systems.

Intravenous anifrolumab is currently approved for the treatment of moderate to severe SLE in more than 70 countries, including the US, EU and Japan. AstraZeneca reported that more than 40,000 patients worldwide have been treated with the therapy to date.

In addition to SLE, anifrolumab continues to be evaluated in other conditions in which type I interferon signaling is implicated, including cutaneous lupus erythematosus, myositis, systemic sclerosis and lupus nephritis.

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