Carla Nester, MD: Pegcetacoplan in C3 Glomerulopathy and Primary IC-MPGN

Full data from the VALIANT trial are providing nephrologist with the greatest insight yet into the benefit of pegcetacoplan (Empaveli) among patients with C3 glomerulopathy (C3G) and primary immune complex membranoproliferative glomerulonephritis (IC-MPGN).

Presented at the American Society of Nephrology’s Kidney Week 2024, results of the trial position pegcetacoplan, a complement inhibitor from Sobi and Apellis Pharmaceuticals, as the first agent to clinically meaningful benefits for proteinuria, C3c staining, and eGFR stabilization.¹

“The results were consistent across patients with different characteristics,” said corresponding author Carla M. Nester, MD, the Jean E. Robillard Chair in Pediatric Nephrology and the director of the Pediatric Glomerular Disease Clinic at the University of Iowa.² “In addition, pegcetacoplan demonstrated favorable safety across native and post-transplant populations.”

A phase 3 trial, VALIANT randomized 124 patients with in a 1:1 ratio to receive 1080 mg of pegcetacoplan or placebo twice weekly for 26 weeks. According to Sobi and Apellis Pharmaceuticals, who announced topline results from the trial in August 2024, VALIANT is the largest single trial conducted in C3G and IC-MPGN populations and the only study to include adolescent and adult patients, with native and post-transplant kidneys.^1,3

Primary endpoint analysis of the trial indicated the mean change in UPCR at week 26 was -67.3% (95% CI, -74.9% to -57.5%) with pegcetacoplan and 3.2% with placebo (95% CI, -8.3% to 16.2%), which corresponds to a relative reduction of 68.3% (95% CI, -76.3% to -57.7%; P <.0001).¹

Analysis of secondary endpoints suggested reduced C3c renal biopsy staining of 2 or more orders of magnitude was observed in 74.3% of the pegcetacoplan group relative to 11.8% in the placebo (Odds Ratio, 27.4; 95% CI, 6.5 to 115.9; nominal P <.0001). Investigators also found adjusted mean change in eGFR favored the pegcetacoplan group, with a mean change of -1.6 (95% CI, -6.0 to 2.8) mL/min/1.73m² with pegcetacoplan relative to -7.9 (95% CI, -11.7 to -4.2) mL/min/1.73m² with placebo group (mean difference, 6.3; 95% CI, 0.5 to 12.1; nominal P = .0322).¹

According to study investigators, the study’s findings place pegcetacoplan as the first therapy to demonstrate clinically meaningful benefits for proteinuria, C3c staining, and eGFR stabilization in patients with C3G or IC-MPGN.^1,3

Safety data from the trial indicated the frequency and severity of treatment-emergent adverse events was similar between both study arms. A total of 4 serious infections occurred in the trial, with 3 occurring in the pegcetacoplan group, but none were attributed to encapsulated bacteria. Investigators pointed out a single death occurred in the pegcetacoplan arm as the result of COVID-19 pneumonia and was considered unrelated to pegcetacoplan.¹

For more perspective on these results, check out our interview with Nester from the conference floor at Kidney Week 2024:

Relevant disclosures for Nester include Apellis, Biocryst, Kira, Novartis, Silence Therapeutics, and Biocryst.

References:

1. Nester CM, Bomback AS, Ariceta Iraola M, et al. VALIANT: A Randomized, Multicenter, Double-Blind, Placebo (PBO)-Controlled, Phase 3 Trial of Pegcetacoplan for Patients with Native or Post-transplant Recurrent Glomerulopathy (C3G) or Primary Immune Complex Membranoproliferative Glomerulonephritis (IC-MPGN). Presented at American Society of Nephrology Kidney Week 2024. San Diego, CA. October 23-27, 2024.
2. American Society of Nephrology. High-Impact Clinical Trials Generate Promising Results for Improving Kidney Health: Part 2. Newswise. October 26, 2024. Accessed October 26, 2024. https://www.newswise.com/articles/high-impact-clinical-trials-generate-promising-results-for-improving-kidney-health-part-2.
3. Apellis Pharmaceuticals, Inc. Apellis and Sobi announce positive topline results from phase 3 valiant study of Pegcetacoplan in C3G and primary IC-MPGN. Apellis Pharmaceuticals, Inc. August 8, 2024. Accessed October 26, 2024. https://investors.apellis.com/news-releases/news-release-details/apellis-and-sobi-announce-positive-topline-results-phase-3.