FDA grants accelerated approval for Ultomiris in IgA nephropathy – AstraZeneca
Alexion, AstraZeneca Rare Disease’s Ultomiris (ravulizumab) has been approved in the US to reduce proteinuria in adults with primary immunoglobulin A nephropathy (IgAN) at risk for disease progression.
This 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 for this indication may be contingent upon verification and description of clinical benefit in the ongoing I CAN Phase III trial evaluating Ultomiris in adults with IgAN who are at risk of disease progression. The trial is ongoing and 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.
The approval follows Priority Review by the FDA based on positive results from a prespecified interim analysis of the I CAN trial. Results showed Ultomiris demonstrated a 43.4% reduction in proteinuria vs placebo at 34 weeks. Ultomiris is administered intravenously every eight weeks in adults (based on body weight), following a loading dose.
IgAN is a rare, inflammatory disease of the kidneys that can lead to chronic kidney disease and progress to end-stage kidney disease (ESKD). It begins when the body develops abnormal IgA proteins resulting in immune complexes that are deposited in the kidneys causing damage. The deposition of these complexes activates the complement system, leading to terminal complement-driven inflammation. This results in damage and loss of essential parts of the kidney, including cells in the glomeruli, the part of the kidneys that filters and cleans the blood. IgAN affects more than 200,000 people in the US. Approximately half of people with IgAN who have elevated protein levels in urine or reduced kidney function are at high risk of progression to ESKD, or kidney failure, within 10 years of diagnosis.
Richard Lafayette, MD, Professor of Medicine (Nephrology) at the Stanford University Medical Center, Founder and Director of the Stanford Glomerular Disease Center and external scientific committee co-chair of the I CAN trial, said: “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. 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.”
Bonnie Schneider, Director & Co-Founder, IgA Nephropathy Foundation, said: “This approval reflects the importance of continued innovation to help improve outcomes for people living with IgAN. 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.”
Marc Dunoyer, Chief Executive Officer, Alexion, said: “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. 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.”
In the prespecified interim analysis from the I CAN Phase III trial, Ultomiris demonstrated a 46.6% reduction in 24-hour urine protein creatinine ratio (UPCR) from baseline (95% confidence interval [CI]: 39.0%, 53.2%) at week 34, compared to 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 rapid, observed as early as week 10 with Ultomiris (36.7% [95% CI: 30.2%, 42.6%]) and sustained through 34 weeks, compared to placebo (8.5% [95% CI: 0.5%, 15.8%]). These 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 was generally well tolerated, with no new safety concerns identified. Based on results from the prespecified interim analysis, the most common adverse events (AE) reported were upper respiratory tract infection (11.3%), nasopharyngitis (9.2%) and infusion-related reactions (8.4%) in those treated with Ultomiris; and upper respiratory tract infection (10.2%), nasopharyngitis (9.0%) and hypertension (6.6%) in those receiving placebo.
The interim results from the I CAN trial were presented at the 2026 European Renal Association (ERA) Congress, and late-breaking results will be presented at the American Society of Nephrology’s Kidney Week on 23 October 2026.
Regulatory submissions based on the interim results from the I CAN trial are also under review in Japan and additional countries.
I CAN (ALXN1210-IgAN-320)
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 immunoglobulin A nephropathy (IgAN) who are at risk of disease progression. Participants were on stable concomitant IgAN treatment(s) consistent with standard of care for at least three months prior to screening. Participants 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 of Ultomiris beginning on Day 15 and then every eight weeks through the 106-week blinded treatment period. Patients who completed the randomised control period had the option to enter an open-label access period. The primary endpoints are change from baseline in proteinuria based on 24-hour urine protein creatinine ratio (UPCR) at week 34 and change from baseline in estimated glomerular filtration rate (eGFR) at week 106, assessed at the interim analysis and final analysis, respectively. Key secondary endpoints for the final analysis include reduction in 24-hour UPCR ≥ 50% from baseline at week 34, change from baseline in proteinuria based on 24-hour UPCR at week 10, time to sustained ≥ 30% eGFR decline up to week 106 and time to first occurrence of 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.
