In a recent press release, AstraZeneca reported that Ultomiris (ravulizumab) has shown a statistically significant and clinically meaningful reduction in proteinuria in adults with immunoglobulin A nephropathy (IgAN), according to results from a prespecified interim analysis of the Phase III I CAN trial. The findings signal potential for terminal complement inhibition as a disease‑modifying strategy in a condition with limited treatment options and a high risk of progression to kidney failure.

The interim analysis demonstrated that patients receiving Ultomiris experienced a significant decrease in proteinuria at week 34, as measured by 24‑hour urine protein creatinine ratio (UPCR), compared with placebo. Notably, reductions were observed early in the treatment course, with improvements detected as soon as week 10. Proteinuria reduction is widely recognized as a key prognostic marker in IgAN, with sustained elevations associated with accelerated loss of kidney function.

While reduction in proteinuria was the primary endpoint for this interim analysis, the study’s second primary endpoint—change in estimated glomerular filtration rate (eGFR)—will be evaluated at week 106, following completion of the full two‑year blinded treatment period.

Targeting complement-driven kidney injury

IgAN is a rare, immune‑mediated kidney disease marked by the deposition of abnormal IgA‑containing immune complexes in the glomeruli. These deposits trigger activation of the complement system, particularly the terminal complement pathway, leading to persistent inflammation and progressive damage to kidney structures. Over time, this injury can result in chronic kidney disease and, in many patients, eventual end‑stage kidney disease requiring dialysis or transplantation.

More than half a million people are estimated to be living with IgAN across the United States, major European markets, and Japan, with a substantial proportion considered eligible for disease‑targeted therapies. Despite advances in supportive care, including optimized blood pressure control and renin–angiotensin system blockade, many patients continue to experience progressive loss of renal function.

Ultomiris is a long‑acting monoclonal antibody designed to inhibit C5, a key component of the terminal complement cascade. By blocking this pathway, the therapy aims to reduce complement‑mediated inflammation and tissue injury—mechanisms believed to play a central role in IgAN progression.

Expert and company perspectives

Commenting on the results, Jonathan Barratt, MD, Mayer Professor of Renal Medicine at the University of Leicester and an investigator in the I CAN trial, noted that many patients with IgAN still progress to kidney failure despite current management strategies. He emphasized that the interim data support terminal complement inhibition as a promising approach for reducing proteinuria, with the potential to meaningfully affect long‑term outcomes once full study results are available.

Marc Dunoyer, Chief Executive Officer of Alexion, AstraZeneca Rare Disease, highlighted the rapid onset of effect seen with Ultomiris and described the proteinuria reduction as both clinically relevant and supportive of a disease‑modifying role in IgAN. The company plans to submit the data to regulatory authorities in key regions and to continue advancing the trial toward completion.

Safety and next steps

The safety profile observed in the I CAN trial was consistent with the established safety experience of Ultomiris across its approved indications. No new safety signals were identified during the interim analysis.

Alexion has indicated its intention to pursue accelerated approval pathways where appropriate and to present the full interim findings at an upcoming scientific meeting. If confirmed in longer‑term analyses, these results could position Ultomiris as one of the first therapies to directly target complement‑driven pathology in IgAN, potentially reshaping the treatment landscape for this progressive kidney disease.

The I CAN trial remains ongoing, with final analyses expected after completion of the 106‑week treatment period.