Apellis Pharmaceuticals and Sobi announced positive results from the Phase 3 VALIANT study, showcasing the potential of systemic pegcetacoplan in treating patients with 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 Kidney Week, highlighted a statistically significant 68.1% reduction in proteinuria among pegcetacoplan-treated patients compared to placebo at Week 26 (p<0.0001). This reduction was observed as early as Week 4 and sustained throughout the six-month treatment period.
Key Findings from the VALIANT Study
The VALIANT study demonstrated that pegcetacoplan not only reduced proteinuria but also stabilized estimated glomerular filtration rate (eGFR), a critical measure of kidney function. Patients treated with pegcetacoplan showed a +6.3mL/min/1.73m2 difference in eGFR over six months compared to placebo. Furthermore, a substantial proportion of patients treated with pegcetacoplan experienced a significant reduction in C3c staining intensity, a key indicator of disease activity.
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 only 11.8% in the placebo group. This translates to 27-fold higher odds of achieving this reduction with pegcetacoplan. Notably, 71.4% of pegcetacoplan-treated patients achieved zero C3c staining intensity, indicating complete clearance of C3c deposits.
Pegcetacoplan also demonstrated 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 drug also showed a numerical improvement in the C3G histologic index activity score.
Safety and Tolerability
During the 26-week randomized, controlled treatment period, pegcetacoplan exhibited 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 reported cases of meningococcal meningitis or serious infections attributed to encapsulated bacteria.
Regulatory Plans and Future Directions
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 (FDA) in early 2025. Sobi intends to submit a marketing application with the European Medicines Agency (EMA) in 2025.
