Alexion Receives FDA Priority Review for Ultomiris as a Potential First C5 Complement Inhibitor Treatment for Adults with IgAN

Alexion Receives FDA Priority Review for Ultomiris as a Potential First C5 Complement Inhibitor Treatment for Adults with IgAN

(IN BRIEF) Alexion, AstraZeneca Rare Disease, has secured FDA acceptance and Priority Review for its supplemental Biologics License Application for Ultomiris as a potential treatment for adults with immunoglobulin A nephropathy, a rare inflammatory kidney disease that can progress to chronic kidney disease and end-stage kidney disease. The application is supported by interim Phase III I CAN trial data showing that Ultomiris achieved a statistically significant and clinically meaningful reduction in proteinuria compared with placebo at week 34, with reductions observed as early as week 10 and maintained through the interim analysis period. If approved, Ultomiris would become the first C5 complement inhibitor available for IgAN, positioning the therapy as a potential disease-modifying option targeting terminal complement-driven inflammation. The FDA’s regulatory decision is expected in the fourth quarter of 2026, while the trial’s longer-term kidney function endpoint based on estimated glomerular filtration rate will be measured at week 106.

(PRESS RELEASE) CAMBRIDGE, 15-Jun-2026 — /EuropaWire/ — Alexion, AstraZeneca Rare Disease, has received acceptance and Priority Review from the US Food and Drug Administration for its supplemental Biologics License Application seeking approval of Ultomiris (ravulizumab) as a treatment for adults with immunoglobulin A nephropathy, a rare kidney disease also known as IgAN.

The FDA grants Priority Review to medicine applications that may provide meaningful improvements over existing treatment options, including advances in safety, efficacy, prevention of serious conditions or patient adherence. The regulatory decision target date under the Prescription Drug User Fee Act is expected in the fourth quarter of 2026.

If approved, Ultomiris would become the first C5 complement inhibitor available for adults with IgAN, a serious inflammatory kidney disease that can lead to chronic kidney disease and may progress to end-stage kidney disease. IgAN develops when abnormal IgA proteins form immune complexes that are deposited in the kidneys, triggering damage. These deposits can activate the complement system and lead to terminal complement-driven inflammation, damaging essential kidney structures, including cells in the glomeruli, which filter and clean the blood. Over time, this damage can reduce kidney function and contribute to long-term disease progression. More than 217,000 people in the US are diagnosed with IgAN.

Marc Dunoyer, Chief Executive Officer of Alexion, said that many people living with IgAN continue to face the risk of progression to end-stage kidney disease despite existing therapies, highlighting the need for additional disease-modifying treatment options. He said the Priority Review reflects the strength of interim data from the I CAN Phase III trial and supports the potential role of Ultomiris in targeting terminal complement-driven inflammation in IgAN.

The sBLA is supported by findings from a prespecified interim analysis of the global Phase III I CAN trial, which were recently presented at the 2026 European Renal Association Congress.

In the trial, Ultomiris showed a 46.6% reduction from baseline in 24-hour urine protein creatinine ratio at week 34, compared with a 5.6% reduction among patients receiving placebo. This resulted in a placebo-adjusted treatment effect of 43.4%, with a 95% confidence interval of 33.5% to 51.8% and a p-value of less than 0.0001.

Proteinuria reduction was observed rapidly, beginning as early as week 10, when patients treated with Ultomiris showed a 36.7% reduction compared with 8.5% in the placebo group. The effect was sustained through week 34 and was consistent across patient subgroups, including individuals with different demographic characteristics, baseline clinical profiles and levels of disease severity. The trial’s primary endpoint measuring change from baseline in estimated glomerular filtration rate will be assessed at week 106.

The safety findings from the I CAN trial were consistent with the established safety profile of Ultomiris. The treatment was generally well tolerated, and no new safety concerns were identified.

Notes

Immunoglobulin A nephropathy is a rare inflammatory kidney disease that may lead to chronic kidney disease and, in some patients, end-stage kidney disease. It is caused by the formation of abnormal IgA proteins that create immune complexes, which accumulate in the kidneys and trigger damage. When these deposits activate the complement system, inflammation can develop through the terminal complement pathway, affecting the glomeruli and reducing the kidneys’ ability to filter blood effectively.

Signs and symptoms of IgAN may include blood in the urine, foamy urine caused by proteinuria, swelling in the hands and feet and high blood pressure. However, many people with the disease experience no symptoms in the early stages, meaning IgAN may go undetected until kidney damage has already occurred. Around half of patients with elevated protein in the urine or reduced kidney function at diagnosis are at risk of progressing to end-stage kidney disease or kidney failure within 10 years.

I CAN, also known as ALXN1210-IgAN-320, is a global Phase III, randomised, double-blind, placebo-controlled trial assessing the efficacy and safety of Ultomiris in adults with IgAN who are considered at risk of disease progression. Participants were receiving stable IgAN treatments aligned with standard of care for at least three months before screening.

Participants were randomised to receive either Ultomiris or placebo through intravenous administration over a 106-week period. Patients assigned to Ultomiris received a loading dose on Day 1, followed by weight-based maintenance dosing beginning on Day 15 and continuing every eight weeks during the blinded treatment period. Patients completing the randomised control period had the option to enter an open-label access period.

The trial’s primary endpoints are change from baseline in proteinuria, based on 24-hour urine protein creatinine ratio at week 34, and change from baseline in estimated glomerular filtration rate at week 106. Secondary measures include the proportion of patients achieving at least a 50% reduction in 24-hour UPCR from baseline at week 34, change in proteinuria at week 10, time to sustained eGFR decline of at least 30% through week 106 and time to the first composite kidney event through week 106. The study was designed to enrol approximately 510 participants across 28 countries in North America, South America, Europe, Asia and Australia.

Ultomiris, or ravulizumab, is a long-acting C5 complement inhibitor designed to provide immediate, complete and sustained inhibition of the terminal complement pathway. It works by inhibiting the C5 protein in the complement cascade, a part of the immune system that can become overactive and contribute to attacks on healthy cells when uncontrolled. After an initial loading dose, Ultomiris is administered intravenously every eight weeks in adults, while paediatric dosing may take place every four or eight weeks depending on body weight.

Ultomiris is approved in the US, European Union, Japan and other markets for certain adults with paroxysmal nocturnal haemoglobinuria and is also approved for certain children with PNH in the US, EU and other countries. It is also approved in multiple markets for certain adults and children with atypical haemolytic uraemic syndrome, as well as for certain adults with generalised myasthenia gravis and neuromyelitis optica spectrum disorder. The therapy is being evaluated in additional indications as part of a broader development programme.

Alexion, AstraZeneca Rare Disease, focuses on developing and delivering medicines for patients and families affected by rare diseases and severe medical conditions. With more than three decades of experience in rare disease, Alexion was among the first companies to translate complement biology into medicines and continues to expand its pipeline across disease areas with significant unmet need. As part of AstraZeneca, Alexion is broadening its international presence to reach more rare disease patients worldwide. The organisation is headquartered in Boston, US.

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SOURCE: AstraZeneca