Apellis Pharmaceuticals and Sobi presented positive results from the Phase 3 VALIANT study at the American Society of Nephrology (ASN) Kidney Week, highlighting the potential of pegcetacoplan in treating C3 glomerulopathy (C3G) and primary immune complex membranoproliferative glomerulonephritis (IC-MPGN). These rare kidney diseases often lead to kidney failure, with current treatments lacking the ability to target the underlying causes.
The VALIANT study (NCT05067127) is the largest trial conducted in C3G and IC-MPGN, including both adolescent and adult patients with native and post-transplant kidneys. The study randomized 124 participants to receive either pegcetacoplan or placebo twice weekly for 26 weeks, in addition to standard of care therapy. The primary endpoint was the log-transformed ratio of urine protein-to-creatinine ratio (uPCR) at Week 26 compared to baseline.
Significant Proteinuria Reduction
Pegcetacoplan-treated patients experienced a statistically significant 68.1% reduction (p<0.0001) in proteinuria compared to placebo at Week 26. This reduction was observed as early as Week 4 and sustained throughout the six-month treatment period. The effect was consistent across various patient subgroups, including those with C3G and IC-MPGN, adolescent and adult patients, and those with native and post-transplant kidneys.
Stabilization of eGFR and Reduction in C3c Staining
Treatment with pegcetacoplan led to stabilization of estimated glomerular filtration rate (eGFR), a critical measure of kidney function. Patients on pegcetacoplan showed a +6.3mL/min/1.73m2 difference (nominal p value=0.03) over six months compared to placebo.
Furthermore, a significant reduction in C3c staining intensity was observed in pegcetacoplan-treated patients. Excessive C3c deposits are a key indicator of disease activity, contributing to kidney inflammation and damage. Specifically:
- 74.3% of patients in the pegcetacoplan group achieved a reduction in C3c staining intensity by two or more orders of magnitude from baseline, compared to 11.8% in the placebo group (nominal p value <0.0001).
- 71.4% of pegcetacoplan-treated patients achieved zero C3c staining intensity, indicating complete clearance of C3c deposits.
Favorable Safety Profile
Pegcetacoplan demonstrated a favorable safety and tolerability profile during the 26-week randomized, controlled period. Rates of treatment-emergent adverse events (AEs), serious AEs, severe AEs, and AEs leading to study discontinuation were similar between the pegcetacoplan and placebo groups. There were no cases of meningococcal meningitis or serious infections attributed to encapsulated bacteria.
Regulatory Plans
Apellis plans to submit a supplemental new drug application to the U.S. Food and Drug Administration in early 2025. Sobi intends to submit a marketing application with the European Medicines Agency in 2025.
"These unprecedented results represent a potential breakthrough for patients living with C3G and IC-MPGN. Pegcetacoplan is the only treatment to achieve substantial and clinically meaningful effects across all key markers of disease: proteinuria, eGFR stabilization, and C3c staining," said Dr. Carla Nester, lead principal investigator for the VALIANT study.
