FDA approves pegcetacoplan as first treatment for C3 glomerulopathy or IC-MPGN

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 aged 12 years and older. According to a press release from the manufacturer, the rare kidney diseases impact 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, multi-center study that evaluated efficacy and safety in 124 patients. Patients were randomized 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 endpoint of the study was the log transformed ratio of urine protein-to-creatinine ratio (UPCR) at Week 26 compared to baseline.

In the largest single trial conducted in these patient populations (those with C3G or IC-MPGN), pegcetacoplan demonstrated a 68% (P < 0.0001) reduction in proteinuria, stabilization of kidney function, and substantial clearance of C3 deposits as measured by C3 staining, compared to placebo. The positive results were consistent across adolescent and adult patients with C3G and primary IC-MPGN, and in C3G patients with post-transplant disease recurrence.

Specifically, pegcetacoplan-treated patients achieved stabilization of kidney function compared to placebo (nominal P = 0.03) as measured by estimated glomerular filtration rate (eGFR). A majority of pegcetacoplan-treated patients achieved a reduction in C3 staining intensity (nominal P < 0.0001) compared to placebo. Seventy-one percent of pegcetacoplan-treated patients achieved 0 C3 staining intensity, 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, 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 suffer from kidney failure within 5 to 10 years of diagnosis, requiring a burdensome kidney transplant or lifelong dialysis therapy. Further, roughly 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, co-founder 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 C3 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. Apellis Pharmaceuticals. Press release. July 28, 2025. Accessed July 29, 2025. https://investors.apellis.com/news-releases/news-release-details/fda-approves-apellis-empavelir-pegcetacoplan-first-c3g-and