RX Review: Updates and Unmet Needs in C3G—The Role of Pegcetacoplan - Episode 5
Unmet Needs and Unanswered Questions in C3G
In the final segment of this 5-part HCPLive RX Review, experts discuss real-world barriers to implementing new C3G therapies and lingering unmet needs.
In the final installment of this HCPLive RX Review, Shikha Wadhwani, MD, MS, Anuja Java, MD, and Corey Cavanaugh, DO, reflect on the promise and challenges of integrating FDA-approved therapies like pegcetacoplan and iptacopan into clinical practice for patients with C3 glomerulopathy (C3G) and immune complex–mediated membranoproliferative glomerulonephritis (IC-MPGN).
While both approvals mark a major step forward, the panel is candid about the real-world barriers that still stand in the way, with access to therapy chief among them. Cavanaugh emphasizes the logistical and financial hurdles in securing these high-cost drugs, even for young patients who may urgently need them. He anticipates that larger academic centers and designated centers of excellence will play a crucial role in helping regional providers navigate these complexities and secure timely treatment.
Java shares the same enthusiasm about having disease-targeted options but flags the persistent frustrations of insurance denials, even for long-established complement inhibitors. Both she and Cavanaugh express ongoing uncertainty about how to apply trial findings to the diverse patient populations seen in practice, especially those with atypical presentations or no clear genetic or functional complement driver. They also grapple with how best to manage transplant patients, many of whom may be on anti-C5 therapy already and raise questions about whether upstream inhibition might offer better long-term outcomes.
The discussion also touches on the lack of predictive tools to determine who will respond to therapy, who will progress, and when and how often repeat biopsies should be performed in seemingly stable patients.
As Wadhwani notes in closing, nephrologists are entering a new era in C3G marked by momentum, collaboration, and the opportunity to finally align pathophysiology with treatment. The panel agrees the key now is to ensure that the promise of clinical trial data translates into equitable, durable outcomes for patients across practice settings.
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
