Ultomiris (ravulizumab) reduced proteinuria in IgA nephropathy patients in the Phase III I CAN trial interim analysis, meeting its primary endpoint at week 34.
Written by: Dr. Anuja Badgujar, BDS
Reviewed By: Pharmacally Editorial Team
Ultomiris (ravulizumab) has demonstrated a statistically significant and clinically meaningful reduction in proteinuria in adults with Immunoglobulin A nephropathy (IgAN), based on a prespecified interim analysis of the Phase III I CAN trial.
The study met its primary endpoint at week 34, showing a reduction in proteinuria measured by 24-hour urine protein creatinine ratio (UPCR), while the second primary endpoint evaluating change in estimated glomerular filtration rate (eGFR) will be assessed at week 106.
IgAN is a rare, progressive kidney disease caused by the deposition of IgA-containing immune complexes in the kidneys, leading to complement-mediated inflammation and gradual loss of kidney function. The disease is often asymptomatic in early stages and may be diagnosed after irreversible damage has occurred.
A significant proportion of patients with elevated proteinuria or impaired kidney function are at risk of progressing to end-stage kidney disease within 10 years.
The I CAN (ALXN1210-IgAN-320) trial is a global, Phase III, randomised, double-blind, placebo-controlled study involving approximately 510 patients with IgAN at risk of progression. Participants received either Ultomiris or placebo intravenously over 106 weeks in addition to standard-of-care therapy, with maintenance dosing every eight weeks following an initial loading dose.
The study evaluated proteinuria reduction at week 34 and eGFR change at week 106 as primary endpoints, with secondary measures including early proteinuria reduction and kidney function outcomes. Interim results showed that ravulizumab reduced proteinuria as early as week 10, indicating an early treatment effect.
Ultomiris is a long-acting C5 complement inhibitor that blocks terminal complement activation, a key driver of inflammation in IgAN, thereby targeting an underlying mechanism of disease progression.
Jonathan Barratt, Professor of Renal Medicine at the University of Leicester and trial investigator, stated that many patients with IgAN continue to progress to kidney failure despite current treatments and noted that complement inhibition with ravulizumab may help reduce proteinuria, a key marker of disease progression, with the full clinical impact to be determined at study completion.
Marc Dunoyer, Chief Executive Officer of Alexion, part of AstraZeneca, highlighted the rapid and clinically meaningful reduction in proteinuria observed as early as week 10 and confirmed plans to advance regulatory submissions while continuing the Phase III trial.
The safety profile was consistent with previous studies, with no new safety concerns identified. Ultomiris carries a boxed warning for serious and potentially life-threatening meningococcal infections, requiring appropriate vaccination prior to treatment.
IgAN remains an area of significant unmet need, and these findings support the potential of complement inhibition as a disease-modifying approach, with implications for future regulatory and clinical development strategies.
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About the Writer
Dr. Anuja Badgujar, BDS is a dentist with expertise in US healthcare data and medical data annotation. With four years of experience handling US healthcare datasets, she brings strong domain knowledge and precision to her work. She is also deeply passionate about medical writing, with a focus on translating complex medical information into clear and structured content.