AstraZeneca’s Alexion has announced positive high level results from a prespecified interim analysis of the I CAN phase III trial. The study found that Ultomiris (ravulizumab) met its primary endpoint, showing a statistically significant and clinically meaningful reduction in proteinuria at week 34. This trial focused on adults with immunoglobulin A nephropathy (IgAN) who are at high risk of disease progression.

Rapid clinical impact and disease modification

The data revealed that Ultomiris delivered a rapid reduction in proteinuria as early as week 10. By inhibiting the terminal C5 complement, the therapy targets a central driver of kidney inflammation. This mechanism suggests that Ultomiris could act as a disease modifying treatment for IgAN, a condition that often leads to chronic kidney disease and eventual kidney failure. While the proteinuria results are a major milestone, the trial will continue until week 106 to measure the final primary endpoint of estimated glomerular filtration rate (eGFR).

Expert and executive perspectives

Jonathan Barratt, MD, a trial investigator from the University of Leicester, noted the significant burden of the disease:

“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. 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.”

Marc Dunoyer, CEO of Alexion, AstraZeneca Rare Disease, highlighted the potential for regulatory action:

“These positive data demonstrate that C5 complement inhibition with Ultomiris results in a rapid and clinically meaningful reduction in proteinuria as early as week 10 and underscores its potential as a disease-modifying approach in IgAN. We look forward to filing these data with regulatory authorities in key regions, while in parallel, advancing this Phase III trial towards completion.”

Safety and market landscape

The safety profile in the I CAN trial remained consistent with previous studies of Ultomiris, with no new safety concerns identified. IgAN is a significant global health issue, with over 560,000 people diagnosed across the US, EU5, and Japan. AstraZeneca intends to pursue accelerated approval in major markets based on these interim results and will present the detailed findings at an upcoming medical conference.