Abstract: SA-PO0826
Clinical Efficacy of Pegcetacoplan vs. Iptacopan in Patients with C3 Glomerulopathy: Indirect Treatment Comparisons
Session Information
- Glomerular Management: Real-World Lessons and Emerging Therapies
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Dixon, Bradley P., University of Colorado School of Medicine, Aurora, Colorado, United States
- Bomback, Andrew S., Columbia University Irvine Medical Center, New York, New York, United States
- Rich, Carly S, Sobi, Stockholm, Sweden
- Huang, Mingyi, Apellis Pharmaceuticals, Inc., Waltham, Massachusetts, United States
- Wojciechowski, Piotr, Clever Access, Kraków, Poland
- Catillon, Maryaline, Analysis Group Inc., New York, New York, United States
- Caravaca-Fontan, Fernando, Instituto de Investigación Hospital 12 de Octubre (imas12), Madrid, Spain
- Fakhouri, Fadi, Lausanne University Hospital, Lausanne, Switzerland
Background
C3 glomerulopathy (C3G) is a rare complement-mediated kidney disease. In the absence of head-to-head randomized-controlled trials (RCTs), anchored indirect treatment comparisons (ITCs) were conducted to assess the relative efficacy of two complement pathway inhibitors, pegcetacoplan (targetedC3/C3b inhibitor) and iptacopan (factor B inhibitor), in patients with C3G.
Methods
Data were extracted from phase 3 RCTs for pegcetacoplan (VALIANT [NCT05067127]) and iptacopan (APPEAR-C3G [NCT04817618]). A common placebo arm in both trials allowed two anchored ITCs to be performed: Bucher method (primary analysis – preserves randomization) and matching-adjusted indirectcomparison (MAIC; supportive analysis – adjusts for trial differences). Relative efficacy was assessed for keyoutcomes, including urine protein to creatinine ratio (UPCR), estimated glomerular filtration rate (eGFR) and composite renal endpoint (≥50% reduction from baseline in UPCR and ≤15% reduction in eGFR). Results were reported as mean or risk difference with 95% confidence intervals.
Results
The Bucher method demonstrated that pegcetacoplan was associated with a significantly greater reduction in UPCR from baseline compared with iptacopan, along with a significantly greater proportion of patients achieving both UPCR reduction to <1 g/g and by ≥50% and the composite renal endpoint (Figure). The change from baseline in eGFR favoured pegcetacoplan versus iptacopan numerically but with no significant differences. Results from the MAIC were generally consistent across these endpoints.
Conclusion
These two ITCs indicate that pegcetacoplan was superior to iptacopan in lowering proteinuria levels and achieving the composite renal endpoint in patients with C3G. The findings from this analysis may help guide clinicians managing patients with this rare condition.
Funding
- Commercial Support – Sobi and Apellis Pharmaceuticals, Inc.