Apellis Pharmaceuticals and Sobi announced positive results from the Phase 3 VALIANT study, showcasing the efficacy of pegcetacoplan in treating C3 glomerulopathy (C3G) and primary immune complex membranoproliferative glomerulonephritis (IC-MPGN). The data, presented at the American Society of Nephrology (ASN) Kidney Week, highlighted significant improvements in key disease markers.
Significant Proteinuria Reduction
Patients treated with pegcetacoplan experienced a statistically significant 68.1% reduction in proteinuria (p<0.0001) compared to placebo at Week 26, when added to standard of care. This reduction was observed as early as Week 4 and sustained throughout the six-month treatment period. The consistency of this effect across various subgroups, including adolescent and adult patients, C3G and IC-MPGN patients, and those with native and post-transplant kidneys, underscores the broad applicability of pegcetacoplan.
Stabilization of eGFR and Reduction in C3c Staining
Pegcetacoplan also demonstrated 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 (nominal p value=0.03) over six months.
Furthermore, a significant proportion of patients treated with pegcetacoplan exhibited a marked reduction in C3c staining intensity, a key indicator of disease activity. Specifically:
- 74.3% of pegcetacoplan-treated patients 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 patients in the pegcetacoplan group achieved zero C3c staining intensity, indicating complete clearance of C3c deposits.
Secondary Endpoint Results and Safety Profile
In addition to the primary outcomes, pegcetacoplan demonstrated statistically significant improvements in key secondary endpoints, including a composite renal endpoint combining proteinuria reduction and eGFR stabilization, as well as a proteinuria reduction of at least 50% compared to baseline. There was also a numerical improvement in the C3G histologic index activity score.
The safety profile of pegcetacoplan was favorable and consistent with previous findings. During the 26-week treatment period, the 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. Notably, there were no cases of meningococcal meningitis or serious infections attributed to encapsulated bacteria.
Regulatory Plans and Future Outlook
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.
These results suggest that pegcetacoplan has the potential to significantly improve the lives of patients with C3G and IC-MPGN by directly targeting C3, the underlying cause of these diseases.
