Ultomiris granted Priority Review in the US as treatment for adults with immunoglobulin A nephropathy

Based on I CAN Phase III trial results from prespecified interim analysis in which Ultomiris demonstrated 43.4% reduction in proteinuria vs placebo at 34 weeks

If approved, Ultomiris would be the first C5 complement inhibitor available for this rare kidney disease

Alexion, AstraZeneca Rare Disease’s supplemental Biologics License Application (sBLA) for Ultomiris (ravulizumab) has been accepted and granted Priority Review by the US Food and Drug Administration (FDA) for the treatment of adults with immunoglobulin A nephropathy (IgAN).

The FDA grants Priority Review to applications for medicines that, if approved, would offer significant improvements over available treatment options by demonstrating safety or efficacy improvements, preventing serious conditions or enhancing patient compliance. The Prescription Drug User Fee Act (PDUFA) date, the FDA action date for its regulatory decision, is anticipated during the fourth quarter of 2026.

IgAN is a rare, inflammatory disease of the kidneys that can lead to chronic kidney disease and progress to end-stage kidney disease. 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 217,000 people are diagnosed with IgAN in the US.²

Marc Dunoyer, Chief Executive Officer, Alexion, said: “Despite available treatments, people living with IgAN often progress to end-stage kidney disease, underscoring the urgent need for new disease-modifying approaches. Building on our pioneering leadership in complement science, this Priority Review reflects the strength of the interim analysis data from the I CAN trial and the potential of Ultomiris as the first C5 complement inhibitor to address terminal complement-driven inflammation in IgAN.”

The sBLA is based on results from a prespecified interim analysis of the I CAN Phase III trial, which were recently presented at the 2026 European Renal Association (ERA) Congress.³

In the trial, Ultomiris demonstrated a 46.6% reduction in 24-hour urine protein creatinine ratio (UPCR) from baseline (95% confidence interval [CI]: 39.0%, 53.2%) at week 34, compared to 5.6% (95% CI: -4.9%, 15.0%) in patients receiving placebo, resulting in a placebo-adjusted treatment effect of 43.4% (95% CI: 33.5%, 51.8%; p less than 0.0001).³

The reduction in proteinuria was rapid, observed as early as week 10 with Ultomiris (36.7% [95% CI: 30.2%, 42.6%]) and sustained through 34 weeks, compared to placebo (8.5% [95% CI: 0.5%, 15.8%]). These results were consistent across patient subgroups, reflecting diverse demographic and baseline clinical characteristics and disease severity.³ The trial’s primary endpoint of change from baseline in estimated glomerular filtration rate (eGFR) will be measured at week 106.⁴

The safety profile observed in the I CAN trial was consistent with the known profile of Ultomiris and was generally well tolerated, with no new safety concerns identified.³

Notes

Immunoglobulin A Nephropathy (IgAN)
Immunoglobulin A nephropathy (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, resulting in chronic kidney disease that can progress to end-stage kidney disease.¹

The signs and symptoms of IgAN can include blood in the urine (haematuria), foamy urine (proteinuria), swelling in hands and feet (oedema) and high blood pressure (hypertension).⁵ Most people with IgAN do not experience symptoms in the early stages of the disease, and therefore, it often goes undetected until it has progressed. At diagnosis, irreversible kidney damage may have already occurred.^6,7 Approximately half of people with IgAN who have elevated protein levels in urine or reduced kidney function are at-risk of progression to ESKD, or kidney failure, within 10 years of diagnosis.⁸

I CAN (ALXN1210-IgAN-320)
I CAN (ALXN1210-IgAN-320) is a global, Phase III, randomised, double-blind, placebo-controlled trial evaluating the efficacy and safety of Ultomiris in adults with immunoglobulin A nephropathy (IgAN) who are at risk of disease progression. Participants were on stable concomitant IgAN treatment(s) consistent with standard of care for at least three months prior to screening.⁴

Participants were randomised 1:1 to receive either Ultomiris or placebo, administered intravenously for a total of 106 weeks. Patients in the treatment arm received a loading dose of Ultomiris on Day 1, followed by regular weight-based maintenance dosing of Ultomiris beginning on Day 15 and then every eight weeks through the 106-week blinded treatment period. Patients who completed the randomised control period had the option to enter an open-label access period.⁴

The primary endpoints are change from baseline in proteinuria based on 24-hour urine protein creatinine ratio (UPCR) at week 34 and change from baseline in estimated glomerular filtration rate (eGFR) at week 106, assessed at the interim analysis and final analysis, respectively. Key secondary endpoints for the final analysis include reduction in 24-hour UPCR more or equal than 50% from baseline at week 34, change from baseline in proteinuria based on 24-hour UPCR at week 10, time to sustained more or equal than 30% eGFR decline up to week 106 and time to first occurrence of composite kidney event up to week 106. The trial was designed to enrol approximately 510 participants from 28 countries across North America, South America, Europe, Asia and Australia.⁴

Ultomiris
Ultomiris (ravulizumab), the longest-acting C5 complement inhibitor, provides immediate, complete and sustained complement inhibition. The medication works by inhibiting the C5 protein in the terminal complement cascade, a part of the body’s immune system. When activated in an uncontrolled manner, the complement cascade over-responds, leading the body to attack its own healthy cells. Following a loading dose, Ultomiris is administered intravenously every eight weeks in adults, or every four or eight weeks in paediatric patients (based on body weight).

Ultomiris is approved in the US, EU, Japan and other countries for the treatment of certain adults with paroxysmal nocturnal haemoglobinuria (PNH) and is also approved for certain children with PNH in the US, EU and other countries.

Ultomiris is also approved in the US, EU, Japan and other countries for the treatment of certain adults and children with atypical haemolytic uraemic syndrome (aHUS).

Additionally, Ultomiris is approved in the US, EU, Japan, China and other countries for the treatment of certain adults with generalised myasthenia gravis (gMG).

Further, Ultomiris is approved in the US, EU, Japan, China and other countries for the treatment of certain adults with neuromyelitis optica spectrum disorder (NMOSD).

Ultomiris is being assessed as a treatment for additional indications as part of a broad development programme.

Alexion
Alexion, AstraZeneca Rare Disease, is focused on serving patients and families affected by rare diseases and devastating conditions through the discovery, development and delivery of life-changing medicines. A pioneering leader in rare disease for more than three decades, Alexion was the first to translate the complex biology of the complement system into transformative medicines, and today it continues to build a diversified pipeline across disease areas with significant unmet need, using an array of innovative modalities. As part of AstraZeneca, Alexion is continually expanding its global geographic footprint to serve more rare disease patients around the world. It is headquartered in Boston, US.

AstraZeneca
AstraZeneca (LSE/STO/NYSE: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Disease, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca’s innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on Social Media @AstraZeneca.

References

1. Cheung CK, et al. The pathogenesis of IgA nephropathy and implications for treatment. Nat Rev Nephrol. 2025;21(1):9-23. doi:10.1038/s41581-024-00885-3. Epub 2024 Sep 4.

2. DeCongelio M, et al. The incidence and prevalence of immunoglobulin A nephropathy in the United States. Clin Nephrol. 2025;103(1):19-25.

3. Barratt J, et al. Ravulizumab in IgA nephropathy: a prespecified interim analysis of a randomized phase 3 trial (I CAN). Presented at European Renal Association (ERA) Congress; 2026 Jun 6; Glasgow, Scotland.

4. ClinicalTrials.gov. A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Ravulizumab in Adult Participants With Immunoglobulin A Nephropathy (IgAN). NCT Identifier: NCT06291376. Available here. Accessed June 2026.

5. Rajasekaran A, et al. IgA Nephropathy: An Interesting Autoimmune Kidney Disease. Am J Med Sci. 2021; 361(2):176–194.

6. Kidney Disease: Improving Global Outcomes (KDIGO) IgAN and IgAV Work Group, et al. KDIGO 2025 Clinical Practice Guideline for the Management of Immunoglobulin A Nephropathy (IgAN) and Immunoglobulin A Vasculitis (IgAV). Kidney Int. 2025; 108(4S): S1-S71.

7. Stamellou E, et al. IgA nephropathy. Nat Rev Dis Primers. 2023;9(1):67. doi:10.1038/s41572-023-00476-9.

8. Wong K, et al. Effects of rare kidney diseases on kidney failure: a longitudinal analysis of the UK National Registry of Rare Kidney Diseases (RaDaR) cohort. Lancet. 2024;403(10433):1279-1289.