Fadi Fakhouri, MD, PhD: Pegcetacoplan in Post-Transplant C3 Glomerulopathy and IC-MPGN

New data from the NOBLE trial is providing insight into the safety and efficacy profile of pegcetacoplan among kidney transplant recipients with recurrent C3 glomerulopathy (C3G) and primary immune complex membranoproliferative glomerulonephritis (IC-MPGN).

Presented at the 61st European Renal Association Congress by Fadi Fakhouri, MD, PhD, a professor of nephrology at Lausanne University Hospital, the NOBLE trial randomized 22 patients in a 3:1 ratio to subcutaneous pegcetacoplan 1080 mg twice weekly or placebo therapy, with both arms receiving standard care in addition to the assigned therapy. Outcomes of interest for the 40-week open-label portion of the study included the proportion of patients with a reduction in C3c staining at week 52, changes in C3G histologic index activity score from baseline to week 52 on kidney biopsy, and evolutions of eGFR, urine protein-to-creatinine ratio (UPCR), serum C3, and sC5b-9 over time.

Primary results of the 12-week, double-blind portion of the trial showed that 80% of patients treated with pegcetacoplan experienced a reduction in C3c staining by 1 or more orders of magnitude of intensity from baseline, and 40% of patients showed 0 staining intensity. Overall, 11 of the 13 patients who completed NOBLE through week 52 were included in the ERA 24 analysis.

Among the 11 patients in the pegcetacoplan arm with available data at week 52, results indicated 64% showed a reduction in C3c staining by 2 or more orders of magnitude of intensity from baseline, 55%, including IC-MPGN patients, showed 0 C3c staining intensity, and 64% had 0 inflammation according to the activity score of the C3G histologic index. Further analysis suggested that eGFR remained stable or improved in 75% of patients, and reductions in proteinuria were observed among those with a UPCR of 1000 mg/g or greater at baseline.

An analysis of safety and tolerability demonstrated that 15.4% of patients had less than 80% compliance with the study drug. Additionally, 84.6% of patients experienced treatment-emergent adverse events, with the majority (63.6%) being mild or moderate in nature, which investigators noted was consistent with previously reported results. Investigators also pointed out that no cases of meningitis, graft losses, or deaths were reported.

For more on the trial, check out our interview with Fakhouri:

Relevant disclosures of interest for Fakhouri include Alexion, Apellis, Roche, Novartis, and Vifor.

References:

Fakhouri F, Bomback A, Kavanagh D, et al. Pegcetacoplan maintains early improvements seen in post-transplant recurrent C3G and IC-MPGN: 1-year results from the Phase II NOBLE trial. Abstract presented at 61st European Renal Association Congress. Stockholm, Sweden. May 23-26, 2024.

Apellis Pharmaceuticals, Inc. Positive one-year data from phase 2 study of Pegcetacoplan in post-transplant recurrence of C3G and IC-MPGN presented as late-breaker at ERA Congress. Apellis Pharmaceuticals, Inc. May 24, 2024. Accessed May 26, 2024. https://investors.apellis.com/news-releases/news-release-details/positive-one-year-data-phase-2-study-pegcetacoplan-post.