FDA Grants Priority Review to Ultomiris for IgA Nephropathy

FDA grants Priority Review to Alexion’s Ultomiris for IgA nephropathy after Phase III I CAN trial results showed a 43.4% reduction in proteinuria versus placebo at 34 weeks

Alexion, AstraZeneca Rare Disease’s supplemental Biologics License Application (sBLA) for Ultomiris (ravulizumab) has been accepted and granted Priority Review by the U.S. Food and Drug Administration (FDA) for the treatment of adults with immunoglobulin A nephropathy (IgAN), a rare kidney disease that can progress to kidney failure.

The regulatory filing is supported by positive results from the Phase III I CAN trial, where Ultomiris significantly reduced proteinuria compared with placebo. The FDA is expected to make its decision during the fourth quarter of 2026 under the Prescription Drug User Fee Act (PDUFA) timeline. If approved, Ultomiris would become the first C5 complement inhibitor available for patients with IgAN.

Phase III Trial Shows Significant Proteinuria Reduction

Data from a prespecified interim analysis of the global Phase III I CAN study (NCT06291376) were recently presented at the 2026 European Renal Association (ERA) Congress.

At week 34, patients treated with Ultomiris achieved a 46.6% reduction in 24-hour urine protein-creatinine ratio (UPCR) from baseline, compared with a 5.6% reduction in the placebo group. This translated into a placebo-adjusted treatment effect of 43.4% (95% CI: 33.5% to 51.8%; p<0.0001).

The treatment effect emerged rapidly. Proteinuria reductions were observed as early as week 10, when patients receiving Ultomiris achieved a 36.7% reduction from baseline compared with 8.5% in the placebo arm. The benefit remained consistent through week 34 and was observed across patient subgroups regardless of demographic characteristics, baseline disease severity, or clinical status.

Investigators will continue to follow participants through week 106, when the trial’s final primary endpoint will assess change in estimated glomerular filtration rate (eGFR), a key measure of kidney function and long-term disease progression.

Targeting Complement-Driven Kidney Damage

IgAN develops when abnormal IgA proteins form immune complexes that accumulate in the kidneys. These deposits activate the complement cascade, triggering chronic inflammation and progressive damage to the glomeruli, the kidney’s filtering units.

Ultomiris is a long-acting monoclonal antibody that inhibits complement protein C5, a critical component of the terminal complement pathway. By blocking terminal complement activation, the therapy aims to reduce inflammation-driven kidney injury and slow disease progression.

Approximately 217,000 people in the United States have been diagnosed with IgAN, and many patients remain at risk of progressing to end-stage kidney disease despite currently available treatments.

Safety Profile Remains Consistent

The safety findings from I CAN aligned with the established profile of Ultomiris. Investigators reported no new safety signals, and treatment was generally well tolerated throughout the interim analysis period.

Regulatory Path

Marc Dunoyer, Chief Executive Officer of Alexion, said the Priority Review underscores both the strength of the interim I CAN data and the need for additional disease-modifying treatment options for patients with IgAN.

A positive FDA decision later this year could expand Ultomiris beyond its currently approved indications, which include paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, generalized myasthenia gravis, and neuromyelitis optica spectrum disorder. The upcoming eGFR results from I CAN will further clarify the therapy’s potential to preserve kidney function and alter the long-term course of IgAN.

 Reference

Ultomiris granted Priority Review in the US as treatment for adults with immunoglobulin A nephropathy