Pegcetacoplan Offers Potential Benefit in Post-Transplant C3G, IC-MPGN


The phase 2 NOBLE trial shows pegcetacoplan reduces disease activity in post-transplant C3G and IC-MPGN, with benefits persisting through the 40-week double-blind period.

Fadi Fakhouri, MD, PhD | Credit: University of Lausanne

Fadi Fakhouri, MD, PhD
Credit: University of Lausanne

A phase 2 trial suggests use of pegcetacoplan in patients with post-transplant recurrence of C3 glomerulopathy (C3G) and primary immune complex membranoproliferative glomerulonephritis (IC-MPGN) has returned positive results.

The 1-year results of the NOBLE trial, which were presented at the 61st European Renal Association Congress (ERA 24), build on previous 12-week data from the trial and indicate the benefits observed with pegcetacoplan among this patient population persisted through the 40-week double blind portion of the trial.1

“It is exciting to see that treatment with pegcetacoplan rapidly reduced disease activity in only 12 weeks, and the effects were sustained over the long term,” said lead investigator Fadi Fakhouri, MD, PhD, a professor of nephrology at Lausanne University Hospital.2 “Post-transplant C3G and IC-MPGN patients are likely to experience disease recurrence, putting them at risk of needing another kidney transplant or dialysis. There is a huge need for a treatment that targets the cause of these diseases, and I am very encouraged by these unprecedented results.”

The first randomized controlled trial of pegcetacoplan compared to standard of care in kidney transplant recipients with recurrent C3G or IC-MPGN, NOBLE randomized 22 patients in a 3:1 ratio to subcutaneous pegcetacoplan 1080 mg twice weekly or placebo therapy, with both arms receiving standard of care on top of the assigned therapy. Primary results of the 12-week, double-blind portion of the trial, which were presented at the American Society of Nephrology Kidney Week 2023, 80% of patients treated with pegcetacoplan showed a reduction in C3c staining by 1 or more orders of magnitude of intensity from baseline and 40% of patients showed 0 staining intensity.1,3

Outcomes of interest for the 40-week open-label portion of the study were the proportion of patients with a reduction in C3c staining at Week 52 and changes in C3G histologic index activity score from baseline to Week 52 on kidney biopsy, and evolutions of eGFR, UPCR, serum C3, and sC5b-9 over time. Of note, reduction in C3c staining was defined as 2 or more orders of magnitude.1

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 revealed the following:1

  • 64% of patients showed a reduction in C3c staining by 2 or more orders of magnitude of intensity from baseline
  • 55% of patients including the IC-MPGN patients, showed 0 C3c staining intensity
  • 64% had 0 inflammation according to the activity score of the C3G histologic index

Further analysis suggested 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.1

Analysis of safety and tolerability demonstrated 15.4% of patients had less than 80% compliance with study drug. Additionally, 84.6% patients experienced treatment-emergent adverse events, with the majority being mild or moderate (7/11, 63.6%) in nature, which investigators noted was consistent with previously reported results. Investigators pointed out no meningitis cases, graft losses, or deaths were reported.1

“The NOBLE data further indicate that pegcetacoplan is treating the underlying cause of these diseases by directly targeting C3,” said Caroline Baumal, MD, chief medical officer of Apellis.2 “Our ongoing Phase 3 VALIANT study evaluates the potential of pegcetacoplan in all patients with these rare kidney diseases, and we look forward to sharing the topline results later this year.”


  1. 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.
  2. 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.
  3. Apellis Pharmaceuticals, Inc. Apellis to present positive phase 2 noble results of Pegcetacoplan in post-transplant recurrence of primary IC-MPGN and C3G at Kidney Week. Apellis Pharmaceuticals, Inc. October 17, 2023. Accessed May 26, 2024.
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