Ultomiris wins accelerated U.S. approval after cutting urine protein 43.4% versus placebo
Key Facts
The U.S. Food and Drug Administration granted accelerated approval to AstraZeneca's Ultomiris to reduce proteinuria in adults with primary immunoglobulin A nephropathy at risk of disease progression, according to a company statement dated October 21, 2026. The decision was based on a reduction in urine protein, after the ICAN trial showed a 43.4% reduction versus placebo at week 34. The drug, known generically as ravulizumab, belongs to the group's Alexion rare disease unit. According to AstraZeneca, it became the first and only complement C5 inhibitor approved in the United States to reduce proteinuria in adults with the disease. Marc Dunoyer, chief executive of Alexion, said, "This approval marks the fifth indication for Ultomiris." The decision adds an approved use for the drug within Alexion's treatments, with the new approval limited to adult patients at risk of disease progression.
In the prespecified interim analysis of the ICAN trial, the urine protein-to-creatinine ratio fell 46.6% from baseline in patients receiving Ultomiris, according to AstraZeneca's statement on the study results. The measurement used urine collected over a full day to compare the change from pretreatment protein levels. The corresponding reduction among patients receiving placebo was 5.6% from baseline in the same analysis. The 43.4% figure reported at week 34 represents the placebo-adjusted treatment effect. AstraZeneca said the proteinuria reduction results were "consistent across patient subgroups." This consistency extended to groups differing in demographic and clinical characteristics and disease severity, according to the company.
Ultomiris works by inhibiting the C5 protein in the terminal complement pathway, part of the immune system, according to AstraZeneca's explanation of the drug's mechanism. Treatment in adults begins with a loading dose, followed by maintenance doses administered by intravenous infusion every 8 weeks. The company said in its priority review statement that the trial's interim analysis identified no new safety concerns. It added that the safety profile observed in the analysis was consistent with the drug's established profile. Official safety information, however, warns that Ultomiris increases the risk of serious infections caused by meningococcal bacteria.
Immunoglobulin A nephropathy affects more than 200,000 people in the United States, according to AstraZeneca's estimates in the approval announcement. The risk of disease progression is particularly pronounced in patients with elevated urine protein levels or declining kidney function. According to Investing's coverage of the approval, about half of patients in this category face a high risk of kidney failure within 10 years. On the regulatory front, the accelerated approval followed a priority review of the application to expand the drug's use to treat adults with the condition. AstraZeneca announced on June 15, 2026, that the supplemental biologics license application had been accepted and granted priority review, ahead of the new U.S. decision.
The benefit to kidney function remains under evaluation, as AstraZeneca said, "It has not been established whether Ultomiris slows kidney function decline in patients with immunoglobulin A nephropathy." Continued accelerated approval may be contingent on demonstrating the treatment's clinical benefit. The Food and Drug Administration explains that companies receiving this type of approval remain required to conduct studies to confirm the anticipated clinical benefit. The ICAN trial measures the change in estimated glomerular filtration rate from baseline at week 106 to assess longer-term kidney function. Additional trial results are scheduled to be presented during the American Society of Nephrology's Kidney Week on October 23, 2026, according to AstraZeneca.