Ultomiris Wins FDA Accelerated Approval for Adult IgAN Proteinuria

Alexion, AstraZeneca Rare Disease’s Ultomiris (ravulizumab) has been approved in the United States to reduce proteinuria in adults with primary immunoglobulin A nephropathy (IgAN) at risk of disease progression, AstraZeneca announced (AZN ) on 21 October 2026. The US Food and Drug Administration granted the indication through its accelerated approval pathway based on reduction of proteinuria, following a Priority Review of the application.

Under the accelerated approval framework, it has not been established whether Ultomiris slows kidney function decline in patients with IgAN. Continued approval for the indication may be contingent upon verification and description of clinical benefit in the ongoing I CAN Phase III trial, which will assess the primary endpoint of change from baseline in estimated glomerular filtration rate (eGFR) at week 106, with data intended to support traditional FDA approval.

IgAN is a rare, inflammatory disease of the kidneys that can lead to chronic kidney disease and progress to end-stage kidney disease. It begins when the body develops abnormal IgA proteins, resulting in immune complexes that are deposited in the kidneys and activate the complement system, leading to terminal complement-driven inflammation that damages the glomeruli, the structures that filter and clean the blood. The disease affects more than 200,000 people in the US, and approximately half of people with IgAN who have elevated protein levels in urine or reduced kidney function are at high risk of progression to kidney failure within 10 years of diagnosis. Signs and symptoms can include blood in the urine, foamy urine, swelling in the hands and feet and high blood pressure, and most people do not experience symptoms in the early stages, so the disease often goes undetected until it has progressed.

Richard Lafayette, Professor of Medicine (Nephrology) at Stanford University Medical Center and external scientific committee co-chair of the I CAN trial, said persistent proteinuria remains a significant challenge for many people living with IgAN despite available treatments, signalling ongoing kidney injury and heightened risk of disease progression. “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,” he said.

Bonnie Schneider, Director and Co-Founder of the IgA Nephropathy Foundation, said the approval gives patients and their physicians more choice as they navigate care, pointing to the medicine’s approved use across several other rare diseases and its established safety profile.

Marc Dunoyer, Chief Executive Officer of Alexion, described Ultomiris as the first and only C5 inhibitor approved for the reduction of proteinuria in adults with IgAN and said the decision marks the fifth indication for the medicine. “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,” he said.

Interim Efficacy and Safety Data

The approval was based on positive results from a prespecified interim analysis of the I CAN trial. According to the company, Ultomiris demonstrated a 46.6% reduction in 24-hour urine protein creatinine ratio (UPCR) from baseline (95% confidence interval: 39.0%, 53.2%) at week 34, compared with 5.6% (95% CI: -4.9%, 15.0%) in patients receiving placebo, resulting in a placebo-adjusted treatment effect of 43.4% (95% CI: 33.5%, 51.8%; p<0.0001). The reduction in proteinuria was observed as early as week 10, at 36.7% (95% CI: 30.2%, 42.6%) for Ultomiris versus 8.5% (95% CI: 0.5%, 15.8%) for placebo, and was sustained through 34 weeks. The company reported that the results were consistent across patient subgroups, reflecting diverse demographic and baseline clinical characteristics and disease severity.

The safety profile observed in the trial was consistent with the known profile of Ultomiris and the treatment was generally well tolerated, with no new safety concerns identified, the company stated. The most common adverse events in patients treated with Ultomiris were upper respiratory tract infection (11.3%), nasopharyngitis (9.2%) and infusion-related reactions (8.4%). In the placebo arm, the most common adverse events were upper respiratory tract infection (10.2%), nasopharyngitis (9.0%) and hypertension (6.6%).

The interim results were presented at the 2026 European Renal Association Congress, and late-breaking results from the I CAN trial are scheduled for presentation at the American Society of Nephrology’s Kidney Week on 23 October 2026.

I CAN Trial Design

I CAN (ALXN1210-IgAN-320) is a global, Phase III, randomised, double-blind, placebo-controlled trial evaluating the efficacy and safety of Ultomiris in adults with IgAN who are at risk of disease progression. Participants were on stable concomitant IgAN treatment consistent with standard of care for at least three months prior to screening and were randomised 1:1 to receive either Ultomiris or placebo, administered intravenously for a total of 106 weeks. Patients in the treatment arm received a loading dose of Ultomiris on Day 1, followed by regular weight-based maintenance dosing beginning on Day 15 and then every eight weeks through the blinded treatment period. Patients who completed the randomised control period had the option to enter an open-label access period.

The trial’s primary endpoints are change from baseline in proteinuria based on 24-hour UPCR at week 34, assessed at the interim analysis, and change from baseline in eGFR at week 106, assessed at the final analysis. Key secondary endpoints for the final analysis include a reduction in 24-hour UPCR of at least 50% from baseline at week 34, change from baseline in 24-hour UPCR at week 10, time to a sustained eGFR decline of at least 30% up to week 106 and time to first occurrence of a composite kidney event up to week 106. The trial was designed to enrol approximately 510 participants from 28 countries across North America, South America, Europe, Asia and Australia.

Ultomiris is administered intravenously every eight weeks in adults, based on body weight, following a loading dose. The medicine, which the company describes as the longest-acting C5 complement inhibitor, works by inhibiting the C5 protein in the terminal complement cascade, a part of the body’s immune system that, when activated in an uncontrolled manner, can lead the body to attack its own healthy cells.

Ultomiris is already approved in the US, EU, Japan, China and other countries for certain adults with paroxysmal nocturnal haemoglobinuria (PNH) and for certain children with PNH in the US, EU, China and other countries. It is also approved in the US, EU, Japan and other countries for certain adults and children with atypical haemolytic uraemic syndrome, and in the US, EU, Japan, China and other countries for certain adults with generalised myasthenia gravis and certain adults with neuromyelitis optica spectrum disorder.

Regulatory submissions based on the interim results from the I CAN trial are also under review in Japan and additional countries. The medicine is being assessed as a treatment for further indications as part of a broader development programme.