RX Review: Updates and Unmet Needs in C3G—The Role of Pegcetacoplan - Episode 3
Understanding Pegcetacoplan in C3G with VALIANT Data
In part 3 of this 5-part HCPLive RX Review, experts discuss VALIANT data supporting pegcetacoplan’s approval and how they compare to iptacopan.
The July 2025 US Food and Drug Administration approval of pegcetacoplan (Empaveli) brought not only new hope for patients with C3 glomerulopathy (C3G), but also a new set of clinical questions, particularly around how best to integrate this therapy into current practice.
In episode 3 of this 5-part HCPLive RX Review, Shikha Wadhwani, MD, MS, Anuja Java, MD, and Corey Cavanaugh, DO, discuss the clinical significance of trial data from VALIANT and how these findings may influence treatment sequencing, therapeutic goals, and expectations moving forward.
A major theme in the discussion centers around the 68% reduction in proteinuria observed with pegcetacoplan by week 26 in the VALIANT trial. Both Java and Cavanaugh note that such a dramatic reduction in proteinuria is unprecedented in glomerular disease and highly relevant for both patient counseling and long-term kidney health. The group also references the trial's biopsy data, which showed elimination of C3 deposits in approximately 70% of patients, suggesting true disease modification beyond hemodynamic or anti-inflammatory effects.
The group emphasizes that proteinuria remains one of the strongest predictors of kidney survival in C3G, pointing out that this level of reduction, combined with histologic improvement, signals a shift from merely slowing disease to truly altering its trajectory. Compared with findings from the iptacopan program, the experts note both agents offer clinically meaningful benefit, though pegcetacoplan may show slightly higher magnitude of response in some metrics.
The group also raises practical considerations around treatment strategy, questioning whether clinicians should begin with the newer, targeted complement inhibitors, or reserve them after trialing traditional off-label options like steroids and mycophenolate. As the real-world use of these agents expands, they anticipate evolving practice patterns will help clarify these decisions.
Our Panelists:
- Shikha Wadhwani, MD, MS, is an associate professor of Medicine and the vice chair of Clinical Research at the University of Texas Medical Branch. Wadhwani, who is the co-host of HCPLive’s Kidney Compass podcast and member of our advisory board, serves as the moderator for this conversation.
- Anuja Java, MD, is an associate professor and transplant nephrologist at Washington University School of Medicine in St. Louis and director of Kidney Transplantation at John Cochran VA Medical Center in St. Louis.
- Corey Cavanaugh, DO, is a staff nephrologist at the Cleveland Clinic.
Relevant disclosures for Wadhwani include Otsuka Pharmaceuticals, GSK, Calliditas, and Travere Therapeutics. Relevant disclosures for Java include Alexion, AstraZeneca, Novartis, Dianthus Therapeutics, Aurinia Pharmaceuticals Inc., Apellis and UptoDate. Relevant disclosures for Cavanaugh include Vera Therapeutics and Travere Therapeutics.
References:
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 4, 2025. https://investors.apellis.com/news-releases/news-release-details/fda-approves-apellis-empavelir-pegcetacoplan-first-c3g-and
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
US Food and Drug Administration. Fabhalta approved for complement 3 glomerulopathy. U.S. Food and Drug Administration. Published March 20, 2025. Accessed August 4, 2025. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-first-treatment-adults-complement-3-glomerulopathy-rare-kidney-disease-reduce
