Apellis Pharmaceuticals and Sobi have announced positive results from their Phase 3 VALIANT study, evaluating systemic pegcetacoplan in patients with C3 glomerulopathy (C3G) and primary immune complex membranoproliferative glomerulonephritis (IC-MPGN), rare and debilitating kidney diseases. The findings were presented at the American Society of Nephrology Kidney Week.
Significant Proteinuria Reduction
The study demonstrated a statistically significant 68.1% reduction in proteinuria in pegcetacoplan-treated patients compared to placebo at Week 26, in addition to standard of care. This reduction was observed as early as Week 4 and sustained throughout the six-month treatment period. The consistent reduction across various patient subgroups, including adolescent and adult patients, C3G and IC-MPGN patients, and those with native and post-transplant kidneys, underscores the broad applicability of the treatment.
Stabilization of Kidney Function
Patients treated with pegcetacoplan exhibited stabilization of estimated glomerular filtration rate (eGFR), a critical measure of kidney function. The difference between the pegcetacoplan group and the placebo group was +6.3mL/min/1.73m2 over six months, indicating a preservation of kidney function with pegcetacoplan treatment.
Reduction in C3c Deposits
A substantial proportion of patients treated with pegcetacoplan showed a reduction in C3c staining intensity. Excessive C3c deposits are a key indicator of disease activity, contributing to kidney inflammation, damage, and eventual failure. Notably, 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 only 11.8% in the placebo group. Furthermore, 71.4% of pegcetacoplan-treated patients achieved zero C3c staining intensity, demonstrating complete clearance of C3c deposits.
Secondary Endpoints and Safety Profile
Pegcetacoplan also achieved statistical significance on key secondary endpoints, including a composite renal endpoint combining proteinuria reduction and eGFR stabilization, and proteinuria reduction of at least 50% compared to baseline. The treatment also showed a numerical improvement in the C3G histologic index activity score. During the 26-week treatment period, pegcetacoplan demonstrated a favorable safety and tolerability profile, consistent with its established safety record. Rates of treatment-emergent adverse events, serious adverse events, severe adverse events, and adverse events leading to study discontinuation were similar between the pegcetacoplan and placebo groups. Importantly, there were no cases of meningococcal meningitis or serious infections attributed to encapsulated bacteria.
Regulatory Plans
All patients who completed the VALIANT study have now enrolled in the VALE long-term extension study. Apellis plans to submit a supplemental new drug application to the U.S. Food and Drug Administration in early 2025. Sobi plans to submit a marketing application with the European Medicines Agency in 2025.
