By VETTAPHARMA reporter – Derek Roche: The U.S. Food and Drug Administration (FDA) has granted Priority Review to Alexion, AstraZeneca Rare Disease’s Ultomiris (ravulizumab) for the treatment of adults with immunoglobulin A nephropathy, moving the therapy closer to becoming the first C5 complement inhibitor approved for this rare kidney disease. The regulatory decision is expected in the fourth quarter of 2026.
The supplemental Biologics License Application (sBLA) is supported by results from the prespecified interim analysis of the pivotal Phase 3 I CAN trial (ALXN1210-IgAN-320), recently presented at the 2026 European Renal Association (ERA) Congress. The study demonstrated that Ultomiris significantly reduced proteinuria compared with placebo in adults with immunoglobulin A nephropathy who were at risk of disease progression.
At Week 34, Ultomiris achieved a 46.6% reduction in 24-hour urine protein-to-creatinine ratio (UPCR) from baseline (95% CI: 39.0%–53.2%), compared with a 5.6% reduction with placebo (95% CI: -4.9% to 15.0%). This translated into a 43.4% placebo-adjusted treatment effect (95% CI: 33.5%–51.8%; p<0.0001). Proteinuria reduction was evident as early as Week 10, with a 36.7% reduction in the Ultomiris arm versus 8.5% with placebo, and the benefit was sustained through Week 34 across patient subgroups.
The trial enrolled approximately 510 participants from 28 countries who were receiving stable background standard-of-care therapy. Participants were randomized 1:1 to receive intravenous Ultomiris or placebo for 106 weeks. While the interim analysis evaluated proteinuria at Week 34, the second primary endpoint—change in estimated glomerular filtration rate (eGFR)—will be assessed at Week 106 to determine the therapy’s long-term effect on kidney function.
The safety profile was consistent with the established safety profile of Ultomiris, with no new safety concerns identified during the interim analysis.
If approved, Ultomiris would become the first therapy targeting terminal complement C5 for immunoglobulin A nephropathy, potentially introducing a new disease-modifying approach for patients at risk of progressing to chronic kidney disease and end-stage kidney disease.
Quick FAQs
1. What Is Ultomiris?
Ultomiris (ravulizumab) is a long-acting C5 complement inhibitor that provides sustained inhibition of terminal complement activation and is approved for several complement-mediated diseases.
2. What Happened?
The FDA granted Priority Review to Alexion’s supplemental Biologics License Application for Ultomiris to treat adults with immunoglobulin A nephropathy. A regulatory decision is expected in the fourth quarter of 2026.
3. What Is The I CAN Trial?
The Phase 3 I CAN (ALXN1210-IgAN-320) trial is a global, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of Ultomiris in approximately 510 adults with immunoglobulin A nephropathy at risk of disease progression.
4. What Is Immunoglobulin A Nephropathy?
Immunoglobulin A nephropathy is a rare inflammatory kidney disease caused by the deposition of abnormal IgA immune complexes in the kidneys, leading to complement activation, progressive kidney damage, chronic kidney disease, and potentially end-stage kidney disease.
5. What Were The Key Results?
Ultomiris reduced proteinuria by 46.6% from baseline compared with 5.6% for placebo, resulting in a 43.4% placebo-adjusted treatment effect (p<0.0001). Proteinuria reduction was observed by Week 10 and remained consistent through Week 34.
6. Why Is This Important?
If approved, Ultomiris would become the first C5 complement inhibitor available for immunoglobulin A nephropathy, offering a novel disease-modifying treatment approach for patients at risk of progressive kidney failure.
