RX Review: Updates and Unmet Needs in C3G—The Role of Pegcetacoplan - Episode 4
Approaching Incident C3G in an Era of Targeted Therapies
In part 4 of this 5-part HCPLive RX Review, experts discuss how the availability of new therapeutic options are changing the treatment paradigm in C3G.
The US Food and Drug Administration approval of pegcetacoplan for C3 glomerulopathy (C3G) signals a significant shift in how clinicians approach this ultra-rare kidney disease. With this and iptacopan now available as targeted therapies, nephrologists face new questions about how best to sequence treatments and tailor strategies to individual patients.
In episode 4 of this 5-part HCPLive RX Review, Shikha Wadhwani, MD, MS, Anuja Java, MD, and Corey Cavanaugh, DO, discuss how these new options are changing the treatment paradigm—and why many clinicians may move away from older, off-label immunosuppressants in favor of frontline targeted therapy.
Java explains her growing preference for initiating treatment with complement inhibitors rather than mycophenolate or prednisone. She notes C3G reflects clear alternative pathway dysregulation for which therapies like pegcetacoplan directly address the root cause. Adding short-term steroids may still be helpful in cases of acute inflammation, but she sees less justification for relying on broad immunosuppression as a first-line approach.
Wadhwani echoes this sentiment, noting that although some patients have responded well to older therapies, heterogeneity in disease course and response makes it difficult to predict who will benefit. With FDA-approved drugs now available and supported by randomized trial data she argues that complement inhibition should be strongly considered up front, with patient preference and shared decision-making guiding final choices.
The panel also tackles the complex issue of treatment duration, which remains an open question. They note that in thrombotic microangiopathy, risk stratification based on genetics and disease severity has helped guide long-term therapy decisions, and a similar framework may eventually emerge in C3G. For now, they suggest that patients with persistent circulating nephritic factors or aggressive disease may require longer-term treatment, while others could potentially taper off therapy with careful monitoring and protocol biopsies.
As more real-world experience accumulates, the panel agrees that treatment personalization and ongoing collaboration will be key to optimizing outcomes in this evolving field.
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
