Abstract: SA-PO0679
Pharmacokinetic (PK), Pharmacodynamic (PD), and Exposure-Response (E-R) Analysis of Pegcetacoplan in C3 Glomerulopathy (C3G) and Primary Immune-Complex Membranoproliferative Glomerulonephritis (pIC-MPGN)
Session Information
- Glomerular Diseases: Clinical, Outcomes, and Therapeutics Research - Other
October 24, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Keshavarz, Ali, Apellis Pharmaceuticals Inc, Waltham, Massachusetts, United States
- Kaufmann, Priska, Swedish Orphan Biovitrum AB publ, Stockholm, Stockholm County, Sweden
- Khankin, Eli, Apellis Pharmaceuticals Inc, Waltham, Massachusetts, United States
- Melnick, Joel, Apellis Pharmaceuticals Inc, Waltham, Massachusetts, United States
- Wachtel, Derek, Apellis Pharmaceuticals Inc, Waltham, Massachusetts, United States
- Voruganti, Shiva, Apellis Pharmaceuticals Inc, Waltham, Massachusetts, United States
Background
C3G and pIC-MPGN comprise dysregulated C3 activation and progressive renal injury. Pegcetacoplan (C3/C3b inhibitor) showed clinical benefit, but PK, PD, and E-R relationships are not well defined.
Methods
Data from two phase 2 and one phase 3 randomized C3G/pIC-MPGN studies were analyzed. Population PK and pegcetacoplan/C3 target-mediated drug disposition models (data from 14 clinical studies) and E-R models (data from 3 nephrology studies) were developed to assess relationships among exposure, complement biomarkers, urine protein-to-creatinine ratio (UPCR), and safety.
Results
Pegcetacoplan reached steady-state exposure at weeks 4–8 with consistent concentrations across subgroups. Adolescent weight-adjusted regimens achieved exposures and clinically meaningful UPCR reductions similar to adults (Fig A). Pegcetacoplan led to sustained complement inhibition within 4 weeks, with >95% free C3 suppression across the dosing interval, indicating maximal target engagement. Free C3 returned to baseline within 4 weeks of discontinuation (B). Patient subgroups achieved consistent UPCR reductions. No intrinsic or extrinsic factors, including baseline eGFR or UPCR, had a clinically meaningful impact on exposure or response (C–F). Immunogenicity had no impact on PK, PD, efficacy, or safety. Pegcetacoplan was not associated with adverse safety outcomes within observed exposure and treatment-duration ranges.
Conclusion
At indicated doses for patients ≥12 years, pegcetacoplan provides consistent exposure, rapid, sustained complement inhibition, and clinically meaningful and safe proteinuria reduction. This supports a fixed-dose adult regimen of 1080 mg twice weekly and weight-adjusted adolescent regimen without adjustment for renal function or proteinuria.
Funding
- Commercial Support – Apellis Pharmaceuticals, Inc and Sobi (Swedish Orphan Biovitrum AB)