FDA Accepts Pegcetacoplan (Empaveli) sNDA for C3G, IC-MPGN

Apellis Pharmaceuticals has announced that the US Food and Drug Administration (FDA) has accepted and granted Priority Review designation to the supplemental New Drug Application (sNDA) for pegcetacoplan (Empaveli) for C3 glomerulopathy (C3G) and primary immune complex membranoproliferative glomerulonephritis (IC-MPGN).1

According to an April 1, 2025, press release from the company, the sNDA submission 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. With the sNDA acceptance, a Prescription Drug User Fee Act (PDUFA) target action date of July 28, 2025, has been assigned.1

“EMPAVELI demonstrated clinically meaningful benefits across all three key markers of disease – unprecedented proteinuria reductions, stabilization of kidney function, and substantial clearance of C3c staining,” said Bradley Dixon, MD, a professor of pediatrics and medicine at the University of Colorado School of Medicine and co-investigator of the VALIANT study.1 “Efficacy is critically important when treating C3G and IC-MPGN given the high risk of progression to kidney failure. As a disease-modifying therapy, EMPAVELI has the potential to make a life-changing difference for patients, if approved.”

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 currently approved for the treatment of paroxysmal nocturnal hemoglobinuria as EMPAVELI®/Aspaveli®.1

A phase 3, multicenter, randomized, placebo-controlled, double-blind clinical trial, VALIANT was launched to assess the safety and efficacy of systemic pegcetacoplan among patients ≥ 12 years of age with C3G and primary IC-MPGN. In total, the trial randomly assigned 124 patients in a 1:1 ratio to receive 1080 mg of pegcetacoplan or placebo twice weekly for 26 weeks.1,2

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).1,2

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.1

According to the release, positive results were consistent across patients with C3G and IC-MPGN, adolescents and adults, and native and post-transplant kidney disease. In the trial, pegcetacoplan showed favorable safety and tolerability, consistent with its established profile.1

“This milestone represents a significant step toward our goal of bringing EMPAVELI to people living with C3G and primary IC-MPGN, regardless of their disease type, age, or transplant status,” said Cedric Francois, MD, PhD, chief executive officer and co-founder at Apellis.1 “We look forward to working with the FDA to make this treatment available to patients in need as quickly as possible.”

References

1. Apellis. Apellis Announces FDA Acceptance and Priority Review of the Supplemental New Drug Application for EMPAVELI® (pegcetacoplan) for C3G and Primary IC-MPGN. April 1, 2025. Accessed April 1, 2025. https://investors.apellis.com/news-releases/news-release-details/apellis-announces-fda-acceptance-and-priority-review

2. Campbell P. VALIANT: Pegcetacoplan Offers Benefit for UPCR, eGFR, C3 Staining in C3G, IC-MPGN. HCPLive. October 26, 2024. Accessed April 1, 2025. https://www.hcplive.com/view/valiant-pegcetacoplan-offers-benefit-for-upcr-egfr-c3-staining-in-c3g-ic-mpgn