Apellis Pharmaceuticals and Sobi announced positive results from the Phase 3 VALIANT study, showcasing the potential of pegcetacoplan in treating C3 glomerulopathy (C3G) and primary immune complex membranoproliferative glomerulonephritis (IC-MPGN), rare and debilitating kidney diseases. The data, presented at the American Society of Nephrology (ASN) Kidney Week, highlight significant improvements in key disease markers.
The VALIANT study (NCT05067127) is the largest pivotal trial conducted in C3G and IC-MPGN, including both adolescent and adult patients with native and post-transplant kidneys. The randomized, placebo-controlled, double-blinded, multi-center study evaluated the efficacy and safety of pegcetacoplan in 124 patients aged 12 years and older. Participants received either pegcetacoplan or placebo twice weekly for 26 weeks, in addition to standard of care therapy.
Significant Proteinuria Reduction
Pegcetacoplan-treated patients experienced a statistically significant 68.1% reduction in proteinuria (p<0.0001) compared to placebo at Week 26, as measured by the log-transformed ratio of urine protein-to-creatinine ratio (uPCR). 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 Kidney Function
Treatment with pegcetacoplan led to the stabilization of estimated glomerular filtration rate (eGFR), a critical measure of kidney function. Patients on pegcetacoplan showed a +6.3mL/min/1.73m2 difference in eGFR compared to placebo over six months (nominal p value=0.03).
Reduction in C3c Deposits
Excessive C3c deposits are a key indicator of disease activity, contributing to kidney inflammation, damage, and failure. The VALIANT study demonstrated that pegcetacoplan significantly reduced C3c staining intensity:
- 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
During the 26-week treatment period, pegcetacoplan demonstrated a favorable safety and tolerability profile, consistent with previous findings. The rates of treatment-emergent adverse events (AEs) were similar between the pegcetacoplan (84.1%) and placebo (93.4%) groups. Serious AEs (9.5% vs. 9.8%), severe AEs (4.8% vs. 6.6%), and AEs leading to study discontinuation (1.6% vs. 1.6%) were also comparable. Notably, 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 (FDA) in early 2025. Sobi intends to submit a marketing application with the European Medicines Agency (EMA) in 2025.
About C3G and IC-MPGN
C3G and primary IC-MPGN are rare kidney diseases that can lead to kidney failure, often requiring kidney transplant or lifelong dialysis. Approximately 50% of individuals with these conditions experience kidney failure within 5 to 10 years of diagnosis. These diseases are estimated to affect 5,000 people in the United States and up to 8,000 in Europe.
Expert Commentary
"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.
