Ultomiris delivers significant proteinuria reductions in adults with IgAN throughout the I CAN Phase III trial

A prespecified interim analysis of the I CAN Phase III trial assessing Ultomiris (ravulizumab) has returned positive results, with the therapy producing a statistically significant and clinically meaningful decrease in proteinuria from baseline as measured by 24-hour urine protein creatinine ratio at week 34, when placed alongside placebo. Participants were adults living with immunoglobulin A nephropathy considered to be at risk of their condition worsening over time.

At week 34, Ultomiris brought about a 46.6% decrease in 24-hour UPCR from baseline, while those on placebo recorded just 5.6%, producing a placebo-adjusted treatment effect of 43.4%. The response was not slow to emerge, with a 36.7% reduction in proteinuria already visible at week 10 among those receiving Ultomiris, compared to 8.5% in the placebo group, a benefit that carried through to the end of the assessment period. Findings held up when broken down across subgroups representing varied demographic backgrounds, baseline clinical profiles, and degrees of disease severity.

“For patients with IgAN, terminal complement activation is a key driver of inflammation and progressive loss of kidney function, which can frequently result in end-stage kidney disease. These interim results show that by targeting the terminal complement pathway, Ultomiris delivered a rapid and significant reduction in proteinuria supporting its potential as a disease-modifying treatment for people living with this devastating rare disease,” said Jonathan Barratt, MD, Mayer Professor of Renal Medicine at the University of Leicester, United Kingdom, and I CAN trial investigator.

“These interim data demonstrate an early and significant reduction in proteinuria with benefit seen across subgroups, including patients who are at higher risk of disease progression. Results underscore the important role of terminal complement inhibition in treating IgAN and highlight the potential of Ultomiris as a meaningful new treatment to address the unmet needs of this patient population. We look forward to advancing regulatory filings for approval in key markets, based on these interim data,” said Gianluca Pirozzi, Senior Vice President, Head of Development, Regulatory and Safety, Alexion, AstraZeneca Rare Disease.

Throughout the trial, the safety profile of Ultomiris remained consistent with what has previously been established for the therapy, with tolerability generally reported as good and no previously unseen safety concerns coming to light. Among those treated with Ultomiris, the most frequently occurring adverse events were upper respiratory tract infection (11.3%), nasopharyngitis (9.2%) and infusion-related reactions (8.4%). In the placebo group, upper respiratory tract infection (10.2%), nasopharyngitis (9.0%) and hypertension (6.6%) were the most commonly reported.

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Related Topics and Keywords

AstraZeneca, Phase III trial, proteinuria, Ultomiris