Ultomiris Is the Latest IgA Nephropathy Drug to Win on Proteinuria, Not Proof It Saves Kidneys
AstraZeneca's fifth Ultomiris indication arrives on a proteinuria surrogate, while the week-106 eGFR readout still decides whether the drug actually saves kidneys.
AstraZeneca's Ultomiris entered IgA nephropathy this week on a proteinuria win the label will not convert into a kidney-function claim. The FDA granted accelerated approval for ravulizumab, a C5 complement inhibitor, to reduce proteinuria in adults with primary immunoglobulin A nephropathy at risk of disease progression, AstraZeneca announced late October 2026. The indication followed Priority Review. It has not been established whether Ultomiris slows kidney function decline. Continued approval is contingent on confirmation of clinical benefit in the ongoing I CAN Phase 3 trial, whose confirmatory endpoint is change in estimated glomerular filtration rate at week 106.
That is now a crowded bargain. Novartis already occupies complement at a different node. Filspari already carries full approval tied to slowing kidney-function decline. The newer wave, Ultomiris included, is still riding a proteinuria surrogate. Whether any of the accelerated-approved complement and B-cell drugs will prove they preserve kidney function remains unpaid. Ultomiris brings a proven franchise and intravenous dosing every eight weeks into that argument. It also owes the same week-106 answer as its rivals.
A terminal-complement drug in a protein-spilling disease
IgAN is a rare, inflammatory kidney disease that can progress to chronic kidney disease and end-stage kidney disease. Abnormal IgA proteins form immune complexes that deposit in the kidney, activating the complement system and driving terminal complement-mediated inflammation that damages the glomeruli. The disease affects more than 200,000 people in the US. Roughly half of patients with elevated urine protein or reduced kidney function are at high risk of progressing to kidney failure within 10 years. Ravulizumab is described as the longest-acting C5 complement inhibitor, inhibiting the C5 protein in the terminal complement cascade and providing immediate, complete, sustained complement inhibition. Dosing is intravenous every eight weeks by body weight, after a loading dose.
I CAN is a global, randomized, double-blind, placebo-controlled Phase 3 study designed to enroll about 510 adults from 28 countries. Patients were on stable standard-of-care IgAN therapy for at least three months before screening and randomized 1:1 to intravenous Ultomiris or placebo for 106 weeks. At a prespecified interim analysis at week 34, Ultomiris cut 24-hour urine protein-creatinine ratio by 46.6% from baseline (95% CI 39.0% to 53.2%) versus 5.6% for placebo (95% CI -4.9% to 15.0%), a placebo-adjusted reduction of 43.4% (95% CI 33.5% to 51.8%, p<0.0001). The effect was rapid, seen as early as week 10 (36.7% versus 8.5% for placebo), and sustained through week 34, consistent across subgroups. Safety was consistent with Ultomiris's known profile. The most common adverse events were upper respiratory tract infection (11.3%), nasopharyngitis (9.2%), and infusion-related reactions (8.4%), with no new safety concerns. Late-breaking I CAN results were scheduled to be presented at the American Society of Nephrology Kidney Week on October 23, 2026, the same day this article publishes.
A fifth indication, still a surrogate
IgAN is Ultomiris's fifth US indication, after paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, generalized myasthenia gravis, and neuromyelitis optica spectrum disorder. The drug generated $4.7 billion in global sales in 2025, up 19% at constant currencies. AstraZeneca gained it through its roughly $39 billion acquisition of Alexion in 2020. Those numbers explain why a proteinuria-only IgAN label is still worth chasing. They do not close the gap between hiding protein in the urine and proving the kidney lasts.
Two complement nodes, one unanswered eGFR clock
The IgAN shelf was already full. Tarpeyo (budesonide, Calliditas) and Filspari (sparsentan, Travere) are the two older entrants. Filspari earned full FDA approval in September 2024 as, per Travere, the only non-immunosuppressive treatment that significantly slows kidney-function decline in IgAN. Novartis's Fabhalta (iptacopan), a factor B complement inhibitor, won accelerated approval in August 2024 as the first complement inhibitor for proteinuria reduction in IgAN. Otsuka's Voyxact (sibeprenlimab), an anti-APRIL antibody, won accelerated approval in November 2025. Vera's atacicept (Trutakna), a BAFF/APRIL-targeting therapy, was approved in July 2026. Vertex's povetacicept, another BAFF/APRIL inhibitor, has an FDA decision expected by November 30, 2026.
Ultomiris therefore adds a second, different node of complement inhibition, C5, to a market where Novartis already blocks factor B, and where an older drug has already shown a kidney-function benefit while the entire newer wave rides proteinuria. The eight-week intravenous schedule and the Alexion franchise are real commercial advantages. They do not settle week 106. Until I CAN reports change in eGFR, Ultomiris is another IgAN drug that can hide protein in the urine without yet proving it saves the kidney.