The US Food and Drug Administration (FDA) has granted accelerated approval to ravulizumab-cwvz (Ultomiris) to reduce proteinuria in adults with primary immunoglobulin A nephropathy (IgAN) at risk for disease progression, introducing the first C5 complement inhibitor approved for this indication, AstraZeneca announced in a press release.
The approval was based on reductions in proteinuria observed in the phase 3 I CAN trial. Whether ravulizumab slows kidney function decline in patients with IgAN has not been established.
The ongoing I CAN trial is a global, randomized, double-blind, placebo-controlled study designed to enroll approximately 510 adults with IgAN at risk for disease progression. Participants receiving stable standard-of-care treatment for at least 3 months were randomly assigned 1:1 to intravenous ravulizumab or placebo for 106 weeks.
The trial's primary end points are change from baseline in proteinuria, measured by 24-hour urine protein-to-creatinine ratio (UPCR) at week 34, and change in estimated glomerular filtration rate (eGFR) at week 106.
In a prespecified interim analysis, ravulizumab reduced UPCR by 46.6% from baseline at week 34, compared with 5.6% in the placebo group, yielding a placebo-adjusted treatment effect of 43.4%.
Reductions were observed as early as week 10, when UPCR decreased by 36.7% with ravulizumab compared with 8.5% with placebo. According to the company, the treatment effect was consistent across patient subgroups.
The most frequently reported adverse events with ravulizumab were upper respiratory tract infection (11.3%), nasopharyngitis (9.2%), and infusion-related reactions (8.4%). Corresponding common events in the placebo group included upper respiratory tract infection (10.2%), nasopharyngitis (9.0%), and hypertension (6.6%). AstraZeneca reported no new safety concerns in the interim analysis.
Ravulizumab carries a boxed warning for serious meningococcal infections, including potentially fatal infections, noted in the FDA prescribing information. The agency also noted meningococcal vaccination should be completed or updated at least 2 weeks before treatment initiation unless delaying therapy poses greater risks. Patients may remain susceptible to infection despite vaccination and require monitoring for early signs and symptoms.
Treatment is administered intravenously using weight-based dosing, beginning with a loading dose followed by maintenance dosing every 8 weeks.
The approval followed FDA Priority Review. Continued approval may depend on verification of clinical benefit through the ongoing I CAN trial, which will assess changes in eGFR at week 106. Additional trial findings are scheduled for presentation at the American Society of Nephrology's Kidney Week on October 23.
Sources: AstraZeneca, FDA