Ravulizumab Receives FDA Accelerated Approval for IgA Nephropathy

The US Food and Drug Administration (FDA) has granted accelerated approval to ravulizumab (Ultomiris) to reduce proteinuria in adults with primary IgA nephropathy at risk for disease progression, based on interim data from the phase 3 I CAN trial, according to an October 21, 2026 release for AstraZeneca.¹

The approval makes ravulizumab, a long-acting C5 complement inhibitor, the first and only C5 inhibitor indicated in IgA nephropathy, according to the company.¹

According to the release, continued approval may be contingent on verification of clinical benefit in I CAN, which will assess change in eGFR at week 106 as its final primary endpoint. AstraZeneca noted it has not been established whether ravulizumab slows kidney function decline in IgA nephropathy.¹

“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,” said Richard Lafayette, MD, professor of medicine (nephrology), Stanford University Medical Center, and external scientific committee co-chair of the I CAN trial. “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.”¹

Ravulizumab efficacy in the phase 3 I CAN trial

I CAN (NCT06291376) is a global, randomized, double-blind, placebo-controlled phase 3 trial designed to enroll approximately 510 adults with IgA nephropathy at risk of progression across 28 countries.¹ Participants on stable standard-of-care therapy for at least 3 months were randomized 1:1 to intravenous ravulizumab or placebo for 106 weeks.¹ Ravulizumab is given as a weight-based loading dose on day 1, followed by maintenance dosing on day 15 and every 8 weeks thereafter.¹

In the prespecified interim analysis, ravulizumab reduced 24-hour UPCR by 46.6% from baseline at week 34 (95% CI, 39.0%-53.2%), compared with 5.6% with placebo (95% CI, −4.9% to 15.0%). The placebo-adjusted treatment effect was 43.4% (95% CI, 33.5%-51.8%; P < .0001).¹ Results were consistent across demographic, baseline clinical, and disease-severity subgroups, according to AstraZeneca.¹

Ravulizumab early proteinuria response and safety in IgAN

Proteinuria reductions emerged by week 10, when UPCR had fallen 36.7% from baseline with ravulizumab (95% CI, 30.2%-42.6%) vs 8.5% with placebo (95% CI, 0.5%-15.8%), and were sustained through week 34.¹ Key secondary end points for the final analysis include a UPCR reduction of at least 50% at week 34, time to sustained eGFR decline of at least 30%, and time to a composite kidney event through week 106.¹

AstraZeneca reported a safety profile consistent with the known profile of ravulizumab, with no new safety concerns identified.¹ The most common adverse events with ravulizumab were upper respiratory tract infection (11.3%), nasopharyngitis (9.2%), and infusion-related reactions (8.4%), compared with upper respiratory tract infection (10.2%), nasopharyngitis (9.0%), and hypertension (6.6%) with placebo.¹ As in its other indications, ravulizumab carries a boxed warning for serious meningococcal infections and is available only through a Risk Evaluation and Mitigation Strategy (REMS) program.²

Late-breaking I CAN results are scheduled for presentation at ASN Kidney Week 2026 on October 23 in Denver, and regulatory submissions are under review in Japan and other countries.¹

HCPLive previously reported the interim I CAN proteinuria data presented at the 2026 European Renal Association Congress.³ IgA nephropathy is the fifth indication for ravulizumab, which is also approved for paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, generalized myasthenia gravis, and neuromyelitis optica spectrum disorder.¹

References

1. AstraZeneca. Ultomiris received accelerated approval in the US as first and only C5 complement inhibitor to reduce proteinuria in adults with primary immunoglobulin A nephropathy. Published October 21, 2026. Accessed October 22, 2026. https://www.astrazeneca.com/media-centre/press-releases/2026/ultomiris-approved-in-us-in-igan.html

2. Ultomiris (ravulizumab-cwvz). Prescribing information. Alexion Pharmaceuticals; 2026.

3. HCPLive. Ravulizumab reduces proteinuria as early as week 10 in phase 3 I CAN trial for IgAN. https://www.hcplive.com/view/ravulizumab-reduces-proteinuria-as-early-as-week-10-in-phase-3-i-can-trial-for-igan. Published April 21, 2026. Accessed October 22, 2026.