Pegcetacoplan Sustains Proteinuria Reductions in C3G, IC-MPGN at 52 Weeks

Extended data from the phase 3 VALIANT trial support the sustained efficacy and safety of pegcetacoplan (Empaveli) in patients with C3 glomerulopathy (C3G) or idiopathic immune-complex membranoproliferative glomerulonephritis (IC-MPGN), including adolescents and adults with native or transplanted kidneys.

Presented at the 62nd European Renal Association (ERA 2025) Congress, the 52-week results show continued proteinuria reduction and eGFR stabilization in both treatment-naïve and crossover groups, reinforcing the 26-week data presented at the American Society of Nephrology’s 2024 Scientific Sessions.

“The one-year Phase 3 results are very compelling, confirming EMPAVELI’s sustained benefits across key markers of disease,” said presenting investigator Fadi Fakhouri, MD, PhD, co-lead principal investigator for the VALIANT study and a professor of nephrology at CHUV Lausanne, Switzerland. “Given the high risk of kidney failure, treatment efficacy is incredibly important to C3G and primary IC-MPGN patients, many of whom are in the prime of their lives. These data further underscore the potential of EMPAVELI to make a meaningful difference for patients.”

The trial included a 26-week randomized controlled period where 63 patients received pegcetacoplan and 61 received placebo. All patients then entered a 26-week open-label period with pegcetacoplan 1080 mg administered subcutaneously twice weekly. In total, 93.7% in the pegcetacoplan group and 90.2% in the placebo group completed the full 52-week course.

At week 52, patients treated with pegcetacoplan throughout showed durable proteinuria reductions, with a mean decrease in urine protein-to-creatinine ratio (UPCR) of 67.2% (95% CI, –75.8 to –55.4). Those who switched from placebo to pegcetacoplan during the OLP experienced comparable benefit, with a 51.3% (95% CI, –62.1 to –37.5) reduction in UPCR by week 52.

Additionally, kidney function remained stable throughout for the continuous pegcetacoplan group (LS mean change in eGFR: –1.2 mL/min/1.73 m² at week 26, –3.7 mL/min/1.73 m² at week 52). Investigators also pointed out participants who switched from placebo to pegcetacoplan showed initial eGFR decline of –7.9 mL/min/1.73 m² at week 26 followed by stabilization during the open-label period, with a decline of –4.7 mL/min/1.73 m² observed at week 52.

Safety data suggested pegcetacoplan was generally well tolerated, with treatment-emergent adverse events (TEAEs) occurring in 77.0% of continuous treatment patients and 73.7% of crossover patients. Investigators noted TEAEs were mild or moderate, and infusion-related events decreased with continued therapy. Of note, no deaths or allograft losses were reported, according to investigators.

For more on pegcetacoplan’s long-term potential in C3G and IC-MPGN, and how these results could shift treatment strategies, check out our full interview with Fakhouri from ERA 2025.

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

References:

1. Fakhouri F, Ariceta G, Bomback A, et al. Pegcetacoplan for C3G and primary (idiopathic) IC-MPGN: 52-week results from the phase 3 VALIANT trial show sustained efficacy. Presented at: 62nd European Renal Association Congress. June 04 – 07, 2025. Vienna, Austria.

2. Appellis Pharmaceuticals. Apellis and Sobi Announce EMPAVELI® (pegcetacoplan) Showed Sustained Efficacy at One Year in Phase 3 Study for C3G and Primary IC-MPGN | Apellis Pharmaceuticals, Inc. Apellis Pharmaceuticals, Inc. Published June 6, 2025. Accessed June 6, 2025. https://investors.apellis.com/news-releases/news-release-details/apellis-and-sobi-announce-empavelir-pegcetacoplan-showed