FDA Grants Accelerated Approval to Ultomiris as First C5 Inhibitor for IgA Nephropathy

The FDA has granted accelerated approval to Alexion, AstraZeneca Rare Disease’s ravulizumab (Ultomiris) to reduce proteinuria in adults with primary immunoglobulin A nephropathy (IgAN) at risk of disease progression.¹ Ultomiris is the first and only C5 complement inhibitor approved for this use, according to the company.¹

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

What did the FDA approve?

The approval, which followed priority review granted in June 2026, is based on reduction of proteinuria in a prespecified interim analysis of the Phase 3 I CAN trial.¹,² It has not been established whether Ultomiris slows kidney function decline in patients with IgAN, and continued approval may be contingent on confirmation of clinical benefit in the ongoing trial.¹

Ultomiris is administered intravenously every eight weeks in adults, based on body weight, following a loading dose.¹ IgAN is the fifth indication for the drug, which is also approved for paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, generalized myasthenia gravis, and neuromyelitis optica spectrum disorder.¹

How does ravulizumab work in IgAN?

Ravulizumab is a monoclonal antibody that inhibits C5, a protein in the terminal complement cascade.¹ In IgAN, abnormal IgA proteins form immune complexes that deposit in the kidneys and activate the complement system, leading to terminal complement-driven inflammation that damages the glomeruli, the kidney’s filtering units.¹

According to AstraZeneca, IgAN affects more than 200,000 people in the US, and approximately half of patients with elevated urinary protein or reduced kidney function are at high risk of progressing to kidney failure within 10 years of diagnosis.¹

What did the I CAN trial show?

I CAN is a global, randomized, double-blind, placebo-controlled Phase 3 trial designed to enroll approximately 510 adults on stable standard-of-care IgAN therapy.¹ At Week 34, Ultomiris reduced 24-hour urine protein-creatinine ratio by 46.6% from baseline, compared with 5.6% for placebo, a placebo-adjusted reduction of 43.4% (95% CI, 33.5%-51.8%; P<.0001).¹ The reduction was observed as early as Week 10, at 36.7% with Ultomiris vs 8.5% with placebo, and results were consistent across patient subgroups.¹

The most common adverse events with Ultomiris were upper respiratory tract infection (11.3%), nasopharyngitis (9.2%), and infusion-related reactions (8.4%), and no new safety concerns were identified.¹

How does Ultomiris fit into IgAN treatment?

Ultomiris enters an increasingly crowded field of targeted IgAN therapies, several of which also received accelerated approval based on proteinuria. FDA approved the anti-APRIL antibody sibeprenlimab (Voyxact) in November 2025, and the BAFF and APRIL inhibitor atacicept (Trutakna) in July 2026.³ BioPharm International® reported at the time of the atacicept approval that iptacopan, a complement factor B inhibitor, was approved in 2024. A decision on Vertex’s BAFF and APRIL inhibitor povetacicept is expected by November 30, 2026.³

Complement-driven inflammation is a target across several diseases beyond IgAN. In a BioPharm International interview at BIO 2026, Howard Berman, PhD, chief executive officer of ReAlta Life Sciences, which is developing a therapy that targets complement among other inflammatory pathways, described the value of hitting multiple drivers of tissue damage. “Being able to hit all these targets at once is so critically and verifiably important to ameliorate the disease,” Berman said.

What happens next?

The I CAN trial continues toward its second primary endpoint, change in estimated glomerular filtration rate at Week 106, with data intended to support traditional FDA approval.¹ Late-breaking results will be presented at the American Society of Nephrology’s Kidney Week on October 23, 2026, and regulatory submissions based on the interim results are under review in Japan and other countries.¹

“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,” said Marc Dunoyer, chief executive officer of Alexion.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. Press release. Published October 21, 2026. Accessed October 22, 2026.
2. AstraZeneca. Ultomiris granted Priority Review in the US as treatment for adults with immunoglobulin A nephropathy. Press release. Published June 15, 2026. Accessed October 22, 2026.
3. Vega E. A second B cell drug for IgA nephropathy was approved in July and two more FDA decisions are due by December. Medical Daily. Published July 31, 2026. Accessed October 22, 2026.