Positive high-level results from a prespecified interim analysis of the I CAN Phase III trial showed that Ultomiris (ravulizumab) met its primary endpoint, demonstrating a statistically significant and clinically meaningful reduction of proteinuria, based on 24-hour urine protein creatinine ratio (UPCR), at week 34 in adults with immunoglobulin A nephropathy (IgAN) who are at risk of disease progression. The primary endpoint of change from baseline in estimated glomerular filtration rate (eGFR) will be measured at week 106.

IgAN is a rare, inflammatory disease of the kidneys that can lead to chronic kidney disease (CKD) and progress to end-stage kidney disease (ESKD). It begins when the body develops abnormal IgA proteins resulting in immune complexes that are deposited in the kidneys causing damage. The deposition of these complexes activates the complement system, leading to terminal complement-driven inflammation. This results in damage and loss of essential parts of the kidney, including cells in the glomeruli, the part of the kidneys that filters and cleans the blood. Over time, this damage impacts the ability of the kidneys to function properly.1

More than 560,000 people are diagnosed with IgAN in the US, EU5 and Japan, of which more than 60 percent are eligible for IgAN treatment.2-5

Jonathan Barratt, MD, Mayer Professor of Renal Medicine, University of Leicester, United Kingdom, and I CAN trial investigator, said: "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, Chief Executive Officer, Alexion, AstraZeneca Rare Disease, said: "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."

The safety profile observed in this trial was consistent with the known profile of Ultomiris, with no new safety concerns identified.

The company will seek accelerated approval in key markets and will present these results at a forthcoming medical meeting.