Abstract: SA-PO800
Pegcetacoplan for Post-transplant Recurrent C3 Glomerulopathy (C3G) or Immune Complex Membranoproliferative Glomerulonephritis (IC-MPGN) in NOBLE: 52-Week Patient Evolution
Session Information
- C3G, TMA, MGRS, Amyloidosis, and More
October 26, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Java, Anuja, Washington University in St Louis School of Medicine, St Louis, Missouri, United States
- Bomback, Andrew S., Columbia University Irving Medical Center, New York, New York, United States
- Kavanagh, David, Newcastle University, Newcastle upon Tyne, Tyne and Wear, United Kingdom
- Remuzzi, Giuseppe, Istituto di Ricerche Farmacologiche Mario Negri, Bergamo, Italy
- Sunder-Plassmann, Gere, Medizinische Universitat Wien, Vienna, Austria
- Kanellis, John, Monash Medical Centre, Clayton, Victoria, Australia
- Daina, Erica, Istituto di Ricerche Farmacologiche Mario Negri, Bergamo, Italy
- Walker, Patrick D., Arkana Laboratories, Little Rock, Arkansas, United States
- Wang, Zhongshen, Apellis Pharmaceuticals Inc, Waltham, Massachusetts, United States
- Ahmad, Zurish, Apellis Pharmaceuticals Inc, Waltham, Massachusetts, United States
- Fakhouri, Fadi, Centre Hospitalier Universitaire Vaudois, Lausanne, Vaud, Switzerland
Background
Pegcetacoplan (Peg; targeted C3/C3b inhibitor) may prevent kidney damage in C3G and primary IC-MPGN. NOBLE (NCT04572854) randomized 13 patients with post-transplant recurrent C3G or primary IC-MPGN. At week 12, Peg was well tolerated and showed improvements in histologic, clinical, and biomarker parameters of disease.
Methods
We conducted a post-hoc analysis of 9 NOBLE patients treated with subcutaneous Peg 1080 mg twice weekly plus standard of care for 52 weeks; of these, treatment completers had >80% compliance (n=7).
Results
At week 52, 5/9 (55.6%) patients had reduced C3c staining (p=0.0423 vs baseline). 7/9 (77.8%) had decreased activity score compared to baseline and 2/8 (25%) had absent electron microscopy deposits at week-52 biopsy. Patients with >1 g/g proteinuria at baseline had a median 56.4% decrease in proteinuria (Table). 7/9 (77.8%) patients had stable/improved estimated glomerular filtration rate, and 8/9 (88.9%) had both increased serum C3 and decreased sC5b-9. No meningitis cases, graft losses, or deaths were reported. Non-serious rejection episodes were reported for 2/9 (22.2%) patients. 1 patient (11.1%) discontinued for serious adverse event of weight loss.
Conclusion
By inhibiting the breakdown of C3, Peg achieved meaningful histology improvements for 8/9 (88.9%) patients while also improving disease parameters, increasing serum C3, and decreasing plasma sC5b-9. The Phase 3 VALIANT (NCT05067127) trial will further evaluate the safety and efficacy of Peg in patients with native kidney or post-transplant C3G or primary IC-MPGN.