AstraZeneca faces FDA rejection on Saphnelo lupus injection
Regulator issues Complete Response Letter for subcutaneous formulation as resubmission targets H1 2026 decision
AstraZeneca's ambitions to expand its lupus treatment franchise suffered a setback after US regulators declined to approve a subcutaneous formulation of Saphnelo, issuing a Complete Response Letter that delays the company's plans to offer patients a more convenient at-home administration option.
The pharmaceutical giant said the Food and Drug Administration's decision applies specifically to the subcutaneous (SC) version of anifrolumab, marketed as Saphnelo, for adult patients with systemic lupus erythematosus (SLE). The intravenous formulation of the drug remains approved in the United States and more than 70 other countries, according to company announcements.
AstraZeneca has already submitted additional information to address the FDA's concerns and now expects a decision on the updated application in the first half of 2026. The regulator's rejection, which reportedly occurred on February 3, stands in contrast to the European Union, where the subcutaneous formulation received approval in December 2025.
The Biologics License Application for the subcutaneous version was supported by positive results from the Phase III TULIP-SC trial, which demonstrated a statistically significant and clinically meaningful reduction in disease activity compared with placebo. The trial evaluated 367 patients with moderate to severe SLE who received either a 120mg subcutaneous dose or placebo via a pre-filled syringe, measuring efficacy using the British Isles Lupus Assessment Group based Composite Lupus Assessment at week 52.
The interim safety profile of the subcutaneous formulation was consistent with the known clinical profile of the intravenous infusion, which has been used to treat more than 40,000 patients globally since its approval in 2021. The convenience factor is significant—subcutaneous administration would allow patients to self-administer the treatment once-weekly at home using a pre-filled pen, rather than visiting a clinic for IV infusions.
AstraZeneca shares, which have climbed more than 50% in the past year to a market capitalisation of approximately $288bn, closed at $92.77 on Monday. The company trades at a forward price-to-earnings ratio of 18.2 times, with analysts maintaining an average target price of $101.78, according to market data. Of 11 analysts covering the stock, 10 rate it a buy or strong buy.
The regulatory divergence between the US and European markets highlights the increasingly complex approval pathway for biologics, even when clinical trial data demonstrates positive outcomes. Complete Response Letters are issued when the FDA completes its review but determines that the application cannot be approved in its current form, typically due to issues related to manufacturing facilities, clinical data, or labeling concerns rather than safety questions.
Saphnelo represents an important component of AstraZeneca's immunology portfolio, addressing a chronic autoimmune disease that affects approximately 5 million people worldwide. The subcutaneous formulation was seen as a crucial growth driver that could expand the treatable patient population and improve adherence among those already receiving IV therapy.
The FDA decision delay comes as AstraZeneca continues to diversify beyond its core oncology franchise, which includes blockbuster cancer treatments such as Tagrisso and Lynparza. The company reported quarterly earnings growth of 78% year-over-year in its most recent quarter, with revenue increasing 12% to $58.1 billion over the trailing twelve months.
AstraZeneca said it is working closely with the FDA to expedite the resubmission process, but the extended timeline will likely temper investor expectations for near-term growth from the Saphnelo franchise. The company remains committed to bringing the subcutaneous option to US patients, emphasising the unmet medical need in the lupus community where treatment options remain limited.