Pegcetacoplan (Empaveli; Apellis Pharmaceuticals) is indicated for patients 12 years or older to reduce proteinuria.
FDA approves pegcetacoplan as first treatment for C3 glomerulopathy or IC-MPGN | Image credit: Contemporary Pediatrics
On July 28, 2025, pegcetacoplan (Empaveli; Apellis Pharmaceuticals) became the first treatment for C3 glomerulopathy (C3G) or primary immune complex membranoproliferative glomerulonephritis (IC-MPGN) when the FDA granted approval for patients 12 years or older. According to a press release from the manufacturer, the rare kidney diseases affect approximately 5000 people in the United States. The C3 therapy is approved to reduce proteinuria.
Approval was based on data from the phase 3 VALIANT study (NCT05067127), a randomized, placebo-controlled, double-blinded, multicenter study that evaluated efficacy and safety in 124 patients. Patients were randomly assigned to receive pegcetacoplan or placebo twice weekly for 26 weeks. Following this 26-week randomized, controlled period, patients were able to proceed to a 26-week open-label phase in which all patients received pegcetacoplan. The primary end point of the study was the log-transformed ratio of urine protein to creatinine ratio (UPCR) at week 26 compared with baseline.
In the largest single trial conducted in these patient populations (those with C3G or IC-MPGN), pegcetacoplan demonstrated a 68% (P < .0001) reduction in proteinuria, stabilization of kidney function, and substantial clearance of C3 deposits as measured by C3 staining compared with placebo. The positive results were consistent across adolescent and adult patients with C3G and primary IC-MPGN and in those with C3G with posttransplant disease recurrence.
Specifically, pegcetacoplan-treated patients achieved stabilization of kidney function compared with placebo (nominal P = .03) as measured by estimated glomerular filtration rate. A majority of pegcetacoplan-treated patients achieved a reduction in C3 staining intensity (nominal P < .0001) compared with placebo. Seventy-one percent of pegcetacoplan-treated patients achieved C3 staining intensity of 0, demonstrating complete clearance of C3 deposits.
“I’m excited to now have a highly effective therapy for a broad range of patients living with C3G and primary IC-MPGN,” said Carla Nester, MD, MSA, FASN, professor of internal medicine and pediatrics and director of pediatric nephrology at the University of Iowa Stead Family Children's Hospital and VALIANT lead principal investigator.
"With standard of care, patients living with these rare and severe diseases frequently progress to kidney failure, necessitating lifelong dialysis and/or a kidney transplant. Given the urgent need, particularly in children, the approval of Empaveli marks a pivotal moment in the treatment of rare kidney diseases," said Nester in a statement.
According to Apellis, approximately 50% of people living with C3G and primary IC-MPGN experience kidney failure within 5 to 10 years of diagnosis, requiring a burdensome kidney transplant or lifelong dialysis therapy. Further, approximately 90% of patients who previously received a kidney transplant will experience disease recurrence.
"[Pegcetacoplan] has the potential to be truly transformational for patients with C3G and primary IC-MPGN, who until now have had very few treatment options," said Cedric Francois, MD, PhD, cofounder and CEO of Apellis, in a statement. "In the largest pivotal study of these diseases, [pegcetacoplan] demonstrated its potential to preserve kidney function by controlling all 3 key markers of disease."
The most common adverse reactions in the VALIANT study (≥ 10%) were infusion site reactions, pyrexia, nasopharyngitis, influenza, cough, and nausea. Pegcetacoplan also comes with a boxed warning for serious infections caused by encapsulated bacteria.
Pegcetacoplan is now approved for C3G or IC-MPGN in the United States, joining other indications for paroxysmal nocturnal hemoglobinuria in the United States, European Union, and other countries. The therapy is also under investigation for other rare diseases.
Reference
FDA approves Apellis’ EMPAVELI (pegcetacoplan) as the first C3G and primary IC-MPGN treatment for patients 12 and older. Press release. Apellis Pharmaceuticals. July 28, 2025. Accessed July 29, 2025. https://investors.apellis.com/news-releases/news-release-details/fda-approves-apellis-empavelir-pegcetacoplan-first-c3g-and
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