FDA clears AstraZeneca's Ultomiris for IgAN proteinuria

Alexion, AstraZeneca (AZN) Rare Disease has secured US Food and Drug Administration accelerated approval for Ultomiris (ravulizumab) to reduce proteinuria in adults with primary immunoglobulin A nephropathy (IgAN) who are at risk for disease progression. The decision followed a Priority Review and makes Ultomiris the first and only C5 complement inhibitor approved in the US for this indication. The IgAN authorization represents the fifth approved use for Ultomiris in the US.

The accelerated approval is specifically tied to reductions in proteinuria and applies to adults with primary IgAN at risk of progression, a population for whom elevated urine protein and impaired kidney function can signal a higher chance of developing end‑stage kidney disease.

The regulatory decision is based on a prespecified interim analysis of the Phase III I CAN trial, a randomized, double‑blind, placebo‑controlled study that enrolled 584 adults with IgAN. Participants received intravenous Ultomiris or placebo every eight weeks over a 106‑week blinded treatment period while on stable standard of care.

At week 34, Ultomiris achieved a 46.6% reduction in 24‑hour urine protein creatinine ratio from baseline, compared with a 5.6% reduction for placebo, yielding a placebo‑adjusted reduction of 43.4% (p<0.0001). A treatment effect was evident as early as week 10, when Ultomiris produced a 36.7% reduction in proteinuria versus 8.5% with placebo, and this effect was sustained through week 34 and consistent across patient subgroups.

The ongoing trial’s final primary endpoint is the change from baseline in estimated glomerular filtration rate at week 106, which is intended to support conversion from accelerated to traditional approval. Whether Ultomiris slows kidney function decline in IgAN has not yet been established, and continued approval may be contingent on verification of clinical benefit at this time point.

In the IgAN program, Ultomiris showed a safety profile consistent with its prior indications, with no new safety concerns identified. The most common adverse events included upper respiratory tract infection, reported in 11.3% of patients, nasopharyngitis in 9.2%, and infusion‑related reactions in 8.4%.

Ultomiris is administered intravenously every eight weeks in adults following a loading dose. The drug functions as a C5 complement inhibitor targeting the terminal complement cascade, which in IgAN is activated by immune complex deposition and contributes to inflammation and glomerular damage.

The new indication adds Ultomiris to a growing US treatment market for IgAN that already includes therapies such as Fabhalta (iptacopan), Vanrafia (atrasentan), Filspari (sparsentan) and targeted‑release corticosteroid Tarpeyo (budesonide). While Fabhalta targets complement factor B in the alternative complement pathway, Ultomiris acts downstream by inhibiting C5 in the terminal complement cascade, offering a different complement‑focused mechanism.

Beyond the US, regulatory submissions for Ultomiris in IgAN based on the I CAN interim results are under review in Japan and additional countries. Late‑breaking data from the I CAN trial are scheduled for presentation at the American Society of Nephrology’s Kidney Week on October 23, 2026, which is expected to provide further detail on the proteinuria findings and longer‑term kidney outcomes.