NEW data from the phase 3 VAILANT trial presented at ERA 2025 Congress, highlighted the potential of pegcetacoplan to modify disease progression in patients with C3 glomerulopathy (C3G) and primary immune complex membranoproliferative glomerulonephritis (IC-MPGN), particularly in those presenting with nephrotic-range proteinuria, a group at high risk of kidney failure.
These rare conditions are driven by uncontrolled activation of complement C3, and current off-label therapies primarily target inflammation rather than the underlying pathology. VALIANT is the first large-scale, randomised trial to test whether direct C3 inhibition with pegcetacoplan could make a meaningful impact.
In this post hoc analysis, patients with a baseline urine protein-to-creatinine ratio (UPCR) ≥3 g/g who received pegcetacoplan achieved a 72.1% reduction in proteinuria at Week 26 versus placebo (p<0.0001). Impressively, two-thirds of patients in the treatment group experienced a ≥50% drop in proteinuria, compared with none in the placebo arm.
Equally compelling were improvements in serum albumin, with 66.7% of pegcetacoplan-treated patients achieving normalisation, and in glomerular C3 staining, where 84.6% showed histological improvement. Kidney function, measured by eGFR, was stabilised in the treatment group with a relative improvement of +16.2 mL/min/1.73 m² compared to placebo.
Safety outcomes were reassuring, with comparable adverse event rates across treatment arms, and no treatment-related deaths or discontinuations.
These results suggest that pegcetacoplan may offer a disease-modifying approach for C3G and IC-MPGN, directly addressing the complement-mediated damage that drives progression. For a patient population historically underserved by available therapies, this marks a potentially significant shift in the treatment landscape.
Reference
Vivarelli M et al. Pegcetacoplan Treatment Effect in Patients With Nephrotic Range Proteinuria: Results From the VALIANT Phase 3 Study in Patients With C3G or Primary (Idiopathic) IC-MPGN. Abstract: 3265. ERA Annual Meeting, 4th-7th June, 2025.
