Entering A New Era of C3G Care with Pegcetacoplan, with Carla Nester, MD

Pegcetacoplan’s FDA approval marks a major milestone in the treatment of C3 glomerulopathy (C3G) and immune complex membranoproliferative glomerulonephritis (IC-MPGN), particularly in populations with high unmet need, including transplant recipients and pediatric patients.

In this interview with HCPLive, Carla Nester, MD, the Jean E. Robillard Chair in Pediatric Nephrology and the director of the Pediatric Glomerular Disease Clinic at the University of Iowa, emphasizes how transformational it is to now have 2 approved complement inhibitors—pegcetacoplan, a C3 inhibitor, and iptacopan, a factor B inhibitor—targeting the core enzymes of the alternative pathway.

As a study investigator on the VALIANT trial supporting pegcetacoplan’s approval, Nester points to the 68% reduction in proteinuria and lack of encapsulated bacterial infections, a common concern with complement inhibitors, seen in the trial.

“The fact that we could achieve such a substantial primary endpoint in this study is, from a clinician standpoint, a pretty amazing finding and obviously very satisfying for the approval of this drug,” Nester said, describing its association with long-term kidney function decline.

In comparing the 2 currently-available therapies, Nester says a number of patient/provider preferences may influence treatment decisions, including the fact that one therapy is oral while the other is subcutaneous, their different dosing regimens, and perceptions about the phase 2 data for each drug.

Looking ahead, Nester emphasizes the importance of continued monitoring of long-term kidney outcomes and real-world safety beyond the current 52-week data: “Not to be complacent about the fact that we now have a treating agent, but I can get excited about what's next, and the first thing for me is going to be whether this equates to better renal outcomes over time.”

Additionally, she cites access as a major concern, including getting patients diagnosed earlier, getting them to the right specialists, and ensuring coverage for high-cost therapies. With updated guidelines and expanded awareness, Nester says she hopes these will eventually help move the field toward alternative pathway blockade as a new standard of care.

Editors’ note: Nester reports relevant disclosures with Apellis, Biocryst, Kira, Novartis, Silence Therapeutics, and Biocryst.

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 August 6, 2025. https://investors.apellis.com/news-releases/news-release-details/fda-approves-apellis-empavelir-pegcetacoplan-first-c3g-and

2. Nester CM, Bomback AS, Ariceta G, et al. VALIANT: A Randomized, Multicenter, Double-Blind, Placebo (PBO)-Controlled, Phase 3 Trial of Pegcetacoplan for Patients with Native or Post-transplant Recurrent Glomerulopathy (C3G) or Primary Immune Complex Membranoproliferative Glomerulonephritis (IC-MPGN). Journal of the American Society of Nephrology. 2024;35(10S). doi: 10.1681/asn.2024qdwvz5bg

3. US Food and Drug Administration. Fabhalta approved for complement 3 glomerulopathy. U.S. Food and Drug Administration. Published March 20, 2025. Accessed August 6, 2025. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-first-treatment-adults-complement-3-glomerulopathy-rare-kidney-disease-reduce