FDA grants AstraZeneca's Ultomiris accelerated approval in IgA nephropathy

The US Food and Drug Administration has granted accelerated approval to AstraZeneca's Ultomiris (ravulizumab) to reduce proteinuria in adults with primary IgA nephropathy (IgAN) who are at risk of disease progression, the company said on 21 October 2026 ¹. The drug, sold by AstraZeneca's rare disease unit Alexion, is the first C5 complement inhibitor cleared in the US for the kidney disease, and IgAN is its fifth indication there ¹².

The approval came after a Priority Review and rests on a prespecified interim analysis of I CAN, a global, randomised, double-blind, placebo-controlled Phase III trial designed to enrol about 510 adults in 28 countries ¹. Patients stayed on their stable standard-of-care IgAN treatment for at least three months before screening and then received either Ultomiris or placebo by infusion ¹.

What the trial found

At week 34, 24-hour urine protein creatinine ratio fell 46.6% from baseline on Ultomiris against 5.6% on placebo, a placebo-adjusted effect of 43.4% (95% CI 33.5% to 51.8%, p<0.0001) ¹. The drop appeared early: by week 10 proteinuria was down 36.7% on the drug against 8.5% on placebo ¹. AstraZeneca said the effect held across subgroups defined by demographics, baseline characteristics and disease severity ¹.

The company reported no new safety concerns. Upper respiratory tract infection (11.3%), nasopharyngitis (9.2%) and infusion-related reactions (8.4%) were the commonest adverse events on Ultomiris, against 10.2%, 9.0% and hypertension at 6.6% on placebo ¹. After a loading dose, adults receive the drug intravenously every eight weeks, dosed by body weight ¹.

What it means for the market

The label is narrower than the headline. The approval is based on proteinuria, and AstraZeneca states that it has not been established whether Ultomiris slows the decline of kidney function in IgAN ¹. Keeping the indication may depend on I CAN confirming clinical benefit through its second primary endpoint, change in estimated glomerular filtration rate (eGFR) at week 106, which the company intends to use to support traditional approval ¹.

Ultomiris enters a crowded field. pharmaphorum counts half a dozen new IgAN therapies reaching the US market in the last decade, with more in development, and notes that Roche has reported Phase 3 data for its Ionis-partnered candidate sefaxersen in the same disease ². The commercial base Alexion is extending is already large: Ultomiris brought in $2.58 billion in the first six months of the year across paroxysmal nocturnal haemoglobinuria, atypical haemolytic uraemic syndrome, generalised myasthenia gravis and neuromyelitis optica spectrum disorder ².

The patient pool is defined in the sources. IgAN affects more than 200,000 people in the US, and about half of those with raised urine protein or reduced kidney function are at high risk of kidney failure within 10 years of diagnosis ¹. An eight-weekly infusion competes on convenience as well as efficacy, although neither source compares Ultomiris directly with other IgAN drugs.

For European and other regulators the file is still open. Submissions based on the same interim results are under review in Japan and other countries, according to AstraZeneca ¹². The sources do not mention a European filing.

Marc Dunoyer, chief executive of Alexion, pointed to the remaining gap, saying many patients "continue to face the risk of progression to kidney failure" ¹.

Caveats

The efficacy data come from an interim analysis of a surrogate marker at 34 weeks, and the 106-week eGFR results that would show an effect on kidney function are not yet in ¹². Late-breaking I CAN results are due at the American Society of Nephrology's Kidney Week on 23 October 2026 ¹.