FDA Approves Pegcetacoplan (Empaveli) for C3 Glomerulopathy, IC-MPGN

The US Food and Drug Administration has approved Apellis Pharmaceuticals’ pegcetacoplan (Empaveli) for the treatment of C3 glomerulopathy (C3G) and primary immune complex membranoproliferative glomerulonephritis (IC-MPGN) in patients aged 12 years and older.

Announced on July 28, 2025, the decision is supported by positive 26-week results from the phase 3 VALIANT trial, the largest single trial conducted in patients with C3G and IC-MPGN and the only study to include adolescent and adult patients with native and post-transplant kidneys. The approval indicates the agent for adults and adolescents with C3G or primary IC-MPGN, and post-transplant C3G disease recurrence.

“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, lead principal investigator for the VALIANT study, professor of internal medicine and pediatrics and director of pediatric nephrology, University of Iowa Stead Family Children's Hospital. “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.”

A targeted C3 therapy designed to regulate excessive activation of the complement cascade, pegcetacoplan is being investigated for the treatment of rare diseases across hematology and nephrology. It is approved for the treatment of paroxysmal nocturnal hemoglobinuria and most recently for the treatment of C3G and IC-MPGN.

"This is fabulous news for people living with C3GN and immune complex MPGN, who have had virtually no proven therapies to preserve their kidney function to date. This is a major step forward - and offers major hope - for these patients, including those who have had recurrent C3GN post-transplantation," said HCPLive advisory board member Brendon Neuen, MBBS, PhD, a senior research fellow with the George Institute for Global Health and director of the Kidney Trials Unit with Royal North Shore Hospital. "More broadly, it demonstrates that we can conduct trials to identify better treatments - even for ultra-rare kidney diseases - by harnessing global networks, empowering patients, and collaborating with sponsors and regulatory agencies."

Pegcetacoplan’s safety and efficacy for this indication was assessed in the phase 3, multicenter, randomized, placebo-controlled, double-blind VALIANT trial, which enrolled 124 patients ≥ 12 years of age with C3G and primary IC-MPGN and enrolled them in a 1:1 ratio to receive 1080 mg of pegcetacoplan or placebo twice weekly for 26 weeks.

Data presented at the American Society of Nephrology’s Kidney Week 2024 showed the study met its primary endpoint for log-transformed ratio of urine protein-to-creatinine ratio (UPCR) at week 26 compared with baseline. The mean change in UPCR at week 26 was -67.3% (95% CI, -74.9% to -57.5%) with pegcetacoplan and 3.2% with placebo (95% CI, -8.3% to 16.2%), corresponding to a relative reduction of 68.3% (95% CI, -76.3% to -57.7%; P <.0001).

Additionally, results showed pegcetacoplan-treated patients achieved stabilization of kidney function (nominal P = .03) as measured by eGFR, and a substantial proportion of pegcetacoplan-treated patients achieved a reduction in C3c staining intensity (nominal P <.0001). In total, 71% of pegcetacoplan-treated patients showed complete clearance of C3c staining compared to placebo.

At the European Renal Association (ERA) Congress 2025, 52-week data from the phase 3 VALIANT trial demonstrated sustained efficacy of pegcetacoplan in patients with C3G or IC-MPGN. Patients treated continuously showed a 67.2% mean reduction in UPCR and minimal eGFR decline (–3.7 mL/min/1.73 m²) and those who switched from placebo achieved a 51.3% UPCR reduction and eGFR stabilization. Safety data indicated pegcetacoplan was well tolerated, with treatment-emergent adverse events occuring in in 77.0% of continuous and 73.7% of crossover patients. Investigators noted most of these events were mild or moderate, with no deaths or allograft losses occurring in the trial.

“EMPAVELI has the potential to be truly transformational for patients with C3G and primary IC-MPGN, who until now have had very few treatment options. In the largest pivotal study of these diseases, EMPAVELI demonstrated its potential to preserve kidney function by controlling all three key markers of disease,” said Cedric Francois, MD, PhD, co-founder and chief executive officer, Apellis. “As Apellis’ third approval in four years, this milestone underscores the unique ability of targeting C3 to improve patients’ lives. We are deeply grateful to everyone who made this approval possible and look forward to building on this momentum as we advance pivotal studies of EMPAVELI in other rare kidney diseases.”

References

1. Apellis Pharmaceuticals. FDA Approves Apellis’ EMPAVELI® (pegcetacoplan) as the First C3G and Primary IC-MPGN Treatment for Patients 12 and Older | Apellis Pharmaceuticals, Inc. Apellis Pharmaceuticals, Inc. Published July 28, 2025. Accessed July 28, 2025. https://investors.apellis.com/news-releases/news-release-details/fda-approves-apellis-empavelir-pegcetacoplan-first-c3g-and

2. Brooks A. FDA Accepts Pegcetacoplan (Empaveli) sNDA for C3G, IC-MPGN. HCPLive. April 1, 2025. Accessed July 28, 2025. https://www.hcplive.com/view/fda-accepts-pegcetacoplan-empaveli-snda-c3g-ic-mpgn