AstraZeneca’s Ultomiris achieved a 43% placebo‑adjusted reduction in proteinuria in the Phase III I CAN trial for IgA nephropathy, supporting its potential as a disease‑modifying therapy with consistent safety and broad clinical benefit.
Written By: Shaik Yasmeen, PharmD
Reviewed By: Pharmacally Editorial Team
AstraZeneca reported positive interim Phase III results from the global I CAN trial evaluating Ultomiris (ravulizumab) in adults with immunoglobulin A nephropathy (IgAN), demonstrating a placebo-adjusted 43.4% reduction in proteinuria at week 34.
The findings, presented at the 63rd European Renal Association (ERA) Congress in Glasgow, support the potential of the long-acting C5 inhibitor as a disease-modifying therapy for patients at risk of progression.
Significant and Rapid Proteinuria Reduction
Ultomiris met the trial’s primary endpoint, reducing 24-hour urine protein-creatinine ratio (UPCR) by 46.6% from baseline compared with 5.6% for placebo, resulting in a statistically significant placebo-adjusted treatment effect of 43.4% (95% CI: 33.5%-51.8%; p<0.0001).
The treatment effect emerged rapidly, with a 36.7% reduction in UPCR at week 10 versus 8.5% for placebo, and was sustained through week 34. Benefits were consistent across patient subgroups, including those with differing baseline characteristics and disease severity.
Jonathan Barratt, MD, Mayer Professor of Renal Medicine at the University of Leicester and an I CAN investigator, said the findings demonstrate that targeting terminal complement activation, a key driver of inflammation and kidney function decline in IgAN, can produce rapid and meaningful reductions in proteinuria, supporting the potential of Ultomiris as a disease-modifying treatment.
Targeting a Key Driver of Disease Progression
IgA nephropathy is a progressive kidney disease caused by the deposition of abnormal IgA-containing immune complexes that trigger complement-mediated inflammation and kidney damage. Ultomiris, the longest-acting C5 inhibitor available, blocks terminal complement activation to reduce ongoing injury and potentially slow disease progression.
Safety Profile Remains Consistent
The safety findings were consistent with the established profile of Ultomiris, with no new safety concerns identified. The most common adverse events among Ultomiris-treated patients were upper respiratory tract infection (11.3%), nasopharyngitis (9.2%), and infusion-related reactions (8.4%).
In the placebo arm, the most common adverse events were upper respiratory tract infection (10.2%), nasopharyngitis (9.0%), and hypertension (6.6%). Overall, treatment was generally well tolerated.
Trial Design and Next Steps
The Phase III I CAN trial (NCT06291376) enrolled approximately 510 adults with IgAN across 28 countries who remained at risk of disease progression despite stable standard-of-care therapy. Participants were randomized 1:1 to receive Ultomiris or placebo, administered every eight weeks following a loading dose.
The study’s dual primary endpoints are change in proteinuria at week 34 and change in estimated glomerular filtration rate (eGFR) at week 106. Key secondary endpoints include at least a 50% reduction in proteinuria, change in UPCR at week 10, sustained eGFR decline, and composite kidney outcomes.
Gianluca Pirozzi, Senior Vice President and Head of Development, Regulatory and Safety at Alexion, AstraZeneca Rare Disease, said the data highlight meaningful benefit across patient subgroups, including those at higher risk of progression. AstraZeneca plans regulatory submissions in key markets based on the interim results while continuing the study toward its final eGFR analysis.
Clinical Implications
The interim Phase III data show that Ultomiris delivers rapid, sustained, and clinically meaningful reductions in proteinuria with a favorable safety profile. If the ongoing trial confirms long-term preservation of kidney function, Ultomiris could become an important new treatment option for patients with IgA nephropathy.
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About the Writer
Shaikh Yasmeen (LinkedIn) is a Pharm.D graduate with interests in clinical pharmacy, pharmacovigilance, and medical writing. She has gained experience through hospital clinical postings, patient case reviews, case presentations, and literature evaluation. Passionate about evidence-based healthcare, she is committed to creating accurate and engaging medical content while continuously expanding her professional knowledge.