RX Review: Updates and Unmet Needs in C3G—The Role of Pegcetacoplan - Episode 1
A New Era for C3G Treatment with Pegcetacoplan
In part 1 of this 5-part HCPLive RX Review, experts discuss the current therapeutic landscape for C3G following 2 notable FDA approvals.
The July 2025 US Food and Drug Administration (FDA) approval of pegcetacoplan (Empaveli) for the treatment of C3 glomerulopathy (C3G) and primary immune complex membranoproliferative glomerulonephritis (IC-MPGN) marks a potential watershed moment in nephrology.
Buoyed by results from pivotal trials and representing one of the first targeted complement inhibitors approved for this indication, pegcetacoplan is poised to transform care for patients with these rare, progressive glomerular diseases—many of whom previously faced limited, non-specific treatment options and high risk of disease recurrence after transplant.
In this first episode of a 5-part HCPLive RX Review, moderator Shikha Wadhwani, MD, MS, is joined by Anuja Java, MD, and Corey Cavanaugh, DO, to explore the evolving therapeutic landscape for C3G and the implications of this long-awaited approval.
The discussion opens with reflections on how far the field has come. Historically, patients with C3G, a rare, complement-mediated kidney disease affecting both children and adults, have faced limited treatment options, largely comprising off-label immunosuppressants with inconsistent efficacy and significant side effects. Cavanaugh notes the previous “guessing game” of treatment, often focused on prolonging kidney function until transplant became inevitable.
Now, the approvals of pegcetacoplan and iptacopan represent the first disease-modifying options for C3G, shifting the treatment approach from symptom management to addressing the root cause.
Java emphasizes that this shift is especially impactful in the transplant setting, where recurrence of C3G post-transplant has long been a major challenge. While the inclusion of transplant patients in recent trials is promising, many unanswered questions remain, particularly around prophylactic use, timing of therapy, duration, and monitoring.
The panel agrees this is a pivotal time in the management of rare kidney diseases. For the first time, clinicians can offer patients real hope for preserving kidney function and potentially preventing or delaying transplant.
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
