Pegcetacoplan for post-transplant recurrent c3 glomerulopathy (C3G) or immune complex membranoproliferative glomerulonephritis (IC-MPGN) in noble: 52-week patient evolution.

Abstract

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. Method(s): 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). Result(s): 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(s): 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.