As reported on PharmaBiz, AstraZeneca has announced that the US Food and Drug Administration (FDA) has accepted for review a supplemental Biologics License Application (sBLA) for ravulizumab (Ultomiris) for the treatment of adults with immunoglobulin A nephropathy (IgAN), a rare and progressive kidney disorder. The application has been granted Priority Review status, indicating that regulators believe the therapy could represent a meaningful advancement over current treatment options. A regulatory decision is expected in the fourth quarter of 2026.
IgAN is characterized by the accumulation of abnormal immunoglobulin A (IgA) immune complexes in the kidneys, leading to inflammation and gradual damage to glomeruli, the structures responsible for filtering blood. Over time, this process can impair renal function and may progress to chronic kidney disease or end-stage kidney failure. In the United States, more than 200,000 individuals are estimated to be affected by the condition.
The submission is supported by findings from a prespecified interim analysis of the Phase III I CAN trial, recently presented at the 2026 European Renal Association Congress. In this study, ravulizumab demonstrated a substantial reduction in proteinuria — a key indicator of kidney damage. Patients receiving the therapy experienced an approximate 46% reduction in urine protein-to-creatinine ratio from baseline at 34 weeks, compared with a modest reduction of about 6% in the placebo group. This translated into a placebo-adjusted decrease of over 40%.
Notably, improvements in proteinuria were observed early in the treatment course, emerging within the first 10 weeks and persisting through the duration of the interim analysis period. The therapeutic effect appeared consistent across different patient populations, regardless of demographic or disease characteristics. Longer-term outcomes, including changes in estimated glomerular filtration rate (eGFR), are still being evaluated, with final analysis planned at 106 weeks.
Ravulizumab targets the complement system, specifically inhibiting the C5 protein involved in the terminal complement cascade. This mechanism is particularly relevant in IgAN, where complement activation contributes to inflammation and progressive kidney injury. If approved, ravulizumab would become the first C5 inhibitor indicated for this condition, potentially introducing a new disease-modifying approach.
The safety profile observed in the trial was consistent with previous studies of the drug, and no new safety concerns were identified. The treatment was generally well tolerated among participants.
Experts note that despite available therapies, many patients with IgAN continue to experience disease progression, highlighting the need for more effective interventions. AstraZeneca’s rare disease unit, Alexion, emphasized that complement inhibition could play a key role in addressing underlying disease mechanisms rather than only managing symptoms.
The FDA’s Priority Review designation is reserved for therapies that may significantly improve treatment, diagnosis, or prevention of serious conditions. As such, the upcoming regulatory decision will be closely watched by clinicians and researchers in nephrology, given the ongoing unmet need for innovative treatments in IgAN.
