Ravulizumab Reduces Proteinuria as Early as Week 10 in Phase 3 I CAN Trial for IgAN

Ravulizumab (Ultomiris) reduced proteinuria as early as week 10 and met its primary endpoint at week 34 in a prespecified interim analysis of the phase 3 I CAN trial, demonstrating a statistically significant and clinically meaningful reduction in proteinuria among adults with IgA nephropathy (IgAN).

AstraZeneca announced positive topline results based on the change from baseline in 24-hour urine protein-creatinine ratio (UPCR) at week 34, supporting terminal C5 complement inhibition as a potential disease-modifying approach in IgAN. The trial’s second primary endpoint, change in estimated glomerular filtration rate (eGFR), will be assessed at week 106.

“Many people living with IgAN continue to progress to kidney failure, ultimately requiring dialysis or a transplant—outcomes that can place profound burden on patients’ daily lives—despite advances in care,” said Jonathan Barratt, MD, Mayer Professor of Renal Medicine at the University of Leicester, United Kingdom, and I CAN trial investigator. “The interim I CAN results demonstrate that blocking terminal complement activation, a central driver of kidney inflammation in IgAN, with Ultomiris may play a promising role in reducing proteinuria. We look forward to understanding the full clinical impact of Ultomiris in treating this disease following study completion at two years.”

Ravulizumab inhibits complement protein C5, preventing its cleavage into C5a and C5b-9—key drivers of inflammation and kidney damage. By targeting terminal complement activation, the therapy may reduce inflammation and slow the progression of kidney injury in IgAN.

The global, phase 3, randomized, double-blind, placebo-controlled I CAN (ALXN1210-IgAN-320) trial is evaluating ravulizumab in approximately 510 adults with biopsy-confirmed IgAN across 28 countries. Participants were required to be on stable background therapy consistent with standard of care for at least 3 months prior to screening and were randomized 1:1 to receive ravulizumab or placebo.

Ravulizumab was administered intravenously, beginning with a loading dose followed by weight-based maintenance dosing every 8 weeks for a total treatment duration of 106 weeks.

The primary endpoints are change from baseline in proteinuria (UPCR) at week 34 and change in eGFR at week 106, assessed at the interim and final analyses, respectively. Key secondary endpoints include ≥50% reduction in UPCR at week 34, change in UPCR at week 10, time to sustained ≥30% decline in eGFR, and time to first composite kidney event through week 106.

The safety profile observed in the trial was consistent with the known profile of ravulizumab, with no new safety concerns identified.

AstraZeneca indicated it plans to seek accelerated approval in key markets and will present full data from the trial at an upcoming medical meeting.

Phase 2 data previously presented at Kidney Week 2023 showed greater proteinuria reduction with ravulizumab (40.3%) compared with placebo (10.9%) at 26 weeks, with a treatment effect of 33.1% (90% CI, 14.7-47.5; P = .0012). Ravulizumab is currently approved by the US Food and Drug Administration for the treatment of paroxysmal nocturnal hemoglobinuria in patients aged ≥1 month, as well as several other complement-mediated conditions.

References

1. Ultomiris demonstrated statistically significant and clinically meaningful reduction of proteinuria in adults with immunoglobulin A nephropathy in I CAN Phase III trial. Astrazeneca.com. Published April 21, 2026. Accessed April 21, 2026. https://www.astrazeneca.com/media-centre/press-releases/2026/i-can-phiii-interim-analysis-met-primary-endpoint.html

2. Valentine A. I CAN - ALXN1210-IgAN-320 Study. Igan.org. Published September 4, 2024. Accessed April 21, 2026. https://igan.org/clinical-trial/alxn1210-igan-320-study