FDA Approves Pegcetacoplan for Rare Kidney Diseases C3G, Primary IC-MPGN in Patients 12 and Older

Today, the FDA approved pegcetacoplan (Empaveli; Apellis Pharmaceuticals) as the first treatment for patients 12 years and older with C3 glomerulopathy (C3G) and primary immune complex membranoproliferative glomerulonephritis (IC-MPGN), 2 rare and severe kidney diseases.1

Estimated to affect 5000 people in the US and up to 8000 in Europe, C3G and primary IC-MPGN are debilitating kidney diseases that can lead to kidney failure.2 About 50% of people living with these diseases progress to kidney failure within 5 to 10 years of diagnosis, requiring a kidney transplant or lifelong dialysis. Also, approximately 90% of patients who previously received a kidney transplant experience disease recurrence. Excessive C3 complement (C3c) deposits are a key indicator of disease activity, as they can lead to kidney inflammation, damage, and failure.

Pegcetacoplan is a C3-targeted therapy that is designed to regulate excessive activation of the complement cascade, a part of the body’s immune system that contributes to the onset and progression of many serious diseases. It is already approved by the FDA for treating paroxysmal nocturnal hemoglobinuria and is under investigation for additional rare diseases across hematology and nephrology.

“I’m excited to now have a highly effective therapy for a broad range of patients living with C3G and primary IC-MPGN,” Carla Nester, MD, MSA, FASN, lead principal investigator of the VALIANT trial (NCT05067127) and director of pediatric nephrology at the University of Iowa Stead Family Children's Hospital, said in a press release.1 “...Given the urgent need, particularly in children, the approval of EMPAVELI marks a pivotal moment in the treatment of rare kidney diseases.”

The FDA approved pegcetacoplan (Empaveli; Apellis Pharmaceuticals) as the first treatment for patients 12 years and older with the rare, severe kidney diseases C3 glomerulopathy (C3G) and primary immune complex membranoproliferative glomerulonephritis (IC-MPGN). | Image Credit: Tada Images - stock.adobe.com

The approval was supported by positive results from the phase 3 VALIANT trial at week 26.3 This randomized, placebo-controlled, double-blinded, multicenter study evaluated the efficacy and safety of pegcetacoplan in 124 patients 12 years or older with C3G or primary IC-MPGN. The primary end point was the log-transformed ratio of urine protein to creatinine ratio (UPCR) at week 26 compared with baseline.

Patients were randomized to receive either pegcetacoplan or a placebo twice weekly for 26 weeks. Of the study population, 63 received pegcetacoplan and 61 received a placebo. After the blinded phase, all patients had the opportunity to proceed to a 26-week open-label phase, where they all received pegcetacoplan.

The trial met its primary end point, with patients receiving pegcetacoplan demonstrating a 68% UPCR reduction compared with placebo at week 26 (P < .0001). Patients treated with pegcetacoplan also achieved stabilization of kidney function (nominal P = .03), as measured by estimated glomerular filtration rate. Additionally, a substantial number of patients treated with pegcetacoplan achieved a reduction in C3c staining intensity (nominal P < .0001), with 71% showing complete clearance compared with the placebo group.

The researchers highlighted that the benefits of pegcetacoplan were consistent among patients with C3G and primary IC-MPGN, across adolescents and adults, and in those with either native or posttransplant kidney disease.2 Lastly, they noted that pegcetacoplan’s favorable safety and tolerability profile aligned with previously reported data.

“EMPAVELI demonstrated clinically meaningful benefits across all 3 key markers of disease – unprecedented proteinuria reductions, stabilization of kidney function, and substantial clearance of C3c staining,” Bradley P. Dixon, MD, FASH, professor of pediatrics and medicine at the University of Colorado School of Medicine and VALIANT coinvestigator, said in a press release.2 “…As a disease-modifying therapy, EMPAVELI has the potential to make a life-changing difference for patients…”

References

1. FDA approves Apellis' EMPAVELI (pegcetacoplan) as the first C3G and primary IC-MPGN treatment for patients 12 and older. News release. Apellis. 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. Apellis announces FDA acceptance and priority review of the supplemental new drug application for EMPAVELI (pegcetacoplan) for C3G and primary IC-MPGN. News release. Apellis. April 1, 2025. Accessed July 28, 2025. https://investors.apellis.com/news-releases/news-release-details/apellis-announces-fda-acceptance-and-priority-review
3. Phase III study assessing the efficacy and safety of pegcetacoplan in patients with C3 glomerulopathy or immune-complex membranoproliferative glomerulonephritis (VALIANT). ClinicalTrials.gov. Updated March 13, 2025. Accessed July 28, 2025. https://www.clinicaltrials.gov/study/NCT05067127