Alexion, AstraZeneca Rare Disease’s Ultomiris (ravulizumab) has been approved in the U.S. to reduce proteinuria in adults with primary immunoglobulin A nephropathy (IgAN) at risk for disease progression.

The approval follows Priority Review by the FDA and is based on positive results from a pre-specified interim analysis of the I can Phase III trial, in which Ultomiris demonstrated a 43.4% reduction in proteinuria versus placebo at 34 weeks.^1,2

What are the terms of the approval?

The indication is approved under accelerated approval based on reduction of proteinuria; it has not been established whether Ultomiris slows kidney function decline in patients with IgAN. Continued approval may be contingent on verification of clinical benefit in the ongoing I can Phase III trial, which is assessing the primary endpoint of change from baseline in estimated glomerular filtration rate at week 106, with data intended to support traditional FDA approval.¹

Ultomiris is administered intravenously every eight weeks in adults, dosed by body weight, following a loading dose. Regulatory submissions based on the interim results are also under review in Japan and additional countries.¹

Bonnie Schneider, director and co-founder of the IgA Nephropathy Foundation, frames the approval as expanding patient choice. “This approval reflects the importance of continued innovation to help improve outcomes for people living with IgAN,” she says. “With its approved use across several other rare diseases and established safety profile, Ultomiris provides a new treatment option in IgAN that gives patients—and their physicians—more choice as they navigate their care.”

What does the data show?

In the pre-specified interim analysis, Ultomiris demonstrated a 46.6% reduction in 24-hour urine protein creatinine ratio from baseline at week 34, compared to 5.6% in patients receiving placebo, for a placebo-adjusted treatment effect of 43.4%.^1,2 The reduction was rapid, observed as early as week 10, and sustained through 34 weeks, with results consistent across patient subgroups reflecting diverse demographics and disease severity.¹ The safety profile remained consistent with Ultomiris’s known profile and generally well tolerated, with no new safety concerns identified, with the most common adverse events in treated patients being upper respiratory tract infection (11.3%), nasopharyngitis (9.2%), and infusion-related reactions (8.4%).^1,2

Why does this indication matter?

IgAN is a rare, inflammatory kidney disease that can progress to chronic kidney disease and end-stage kidney disease. The condition begins when the body develops abnormal IgA proteins that form immune complexes depositing in the kidneys, activating the complement system and driving terminal complement-mediated inflammation that damages the glomeruli. IgAN affects more than 200,000 people in the U.S., and roughly half of patients with elevated urine protein levels or reduced kidney function face high risk of progressing to kidney failure within 10 years of diagnosis.

Richard Lafayette, professor of medicine (nephrology) at Stanford University Medical Center and external scientific committee co-chair of the I can trial, points to an unmet treatment gap. “For many people living with IgAN, persistent proteinuria remains a significant challenge despite available treatments, signalling ongoing kidney injury and heightened risk of disease progression,” he says. “With this approval of Ultomiris, physicians now have a C5 inhibitor that delivers sustained terminal complement inhibition, targeting a central driver of kidney inflammation to meaningfully reduce proteinuria in patients living with this progressive disease.”

What’s next?

Interim results from the I can trial were presented at the 2026 European Renal Association Congress, and late-breaking results are scheduled for presentation at the American Society of Nephrology’s Kidney Week on October 23, 2026.¹ The trial continues toward its week-106 eGFR endpoint, which will determine whether Ultomiris progresses from accelerated to traditional FDA approval in this indication.

Alexion CEO Marc Dunoyer positions the approval within the company’s broader complement-disease franchise. “As the first and only C5 inhibitor approved for the reduction of proteinuria in adults with IgAN, Ultomiris offers a new treatment option for people living with this serious disease,” he says. “Many patients continue to face the risk of progression to kidney failure, underscoring the need for more targeted therapies that can slow the course of disease. This approval marks the fifth indication for Ultomiris, building on Alexion’s pioneering leadership across multiple complement-mediated rare diseases.”

Sources

1. Ultomiris received accelerated approval in the US as first and only C5 complement inhibitor to reduce proteinuria in adults with primary immunoglobulin A nephropathy AstraZeneca October 21, 2026, https://www.astrazeneca.com/media-centre/press-releases/2026/ultomiris-approved-in-us-in-igan.html
2. Ultomiris demonstrated statistically significant and clinically meaningful reduction of proteinuria in adults with immunoglobulin A nephropathy in I CAN Phase III trial AstraZeneca April 21, 2026, https://www.astrazeneca.com/media-centre/press-releases/2026/i-can-phiii-interim-analysis-met-primary-endpoint.html