Full results from the Phase 3 VALIANT trial reveal that pegcetacoplan (Empaveli) provides clinically meaningful benefits for patients suffering from C3 glomerulopathy (C3G) and primary immune complex membranoproliferative glomerulonephritis (IC-MPGN). The study, presented at the American Society of Nephrology's Kidney Week 2024, positions pegcetacoplan as the first agent to demonstrate significant improvements in proteinuria, C3c staining, and eGFR stabilization in this patient population.
The VALIANT trial, the largest study conducted in C3G and IC-MPGN, randomized 124 patients in a 1:1 ratio to receive either 1080 mg of pegcetacoplan or placebo twice weekly for 26 weeks. The study included both adolescent and adult patients with native and post-transplant kidneys.
Significant Reduction in Proteinuria
The primary endpoint analysis showed a substantial reduction in proteinuria, with the mean change in urine protein to creatinine ratio (UPCR) at week 26 being -67.3% (95% CI, -74.9% to -57.5%) in the pegcetacoplan group compared to 3.2% (95% CI, -8.3% to 16.2%) in the placebo group. This corresponds to a relative reduction of 68.3% (95% CI, -76.3% to -57.7%; P <.0001).
Impact on C3c Staining
Secondary endpoint analysis revealed that a reduction of C3c renal biopsy staining of 2 or more orders of magnitude was observed in 74.3% of the pegcetacoplan group compared to only 11.8% in the placebo group (Odds Ratio, 27.4; 95% CI, 6.5 to 115.9; nominal P <.0001).
Stabilization of eGFR
Researchers also found that the adjusted mean change in estimated glomerular filtration rate (eGFR) favored the pegcetacoplan group, with a mean change of -1.6 (95% CI, -6.0 to 2.8) mL/min/1.73m² with pegcetacoplan compared to -7.9 (95% CI, -11.7 to -4.2) mL/min/1.73m² with placebo (mean difference, 6.3; 95% CI, 0.5 to 12.1; nominal P = .0322).
Favorable Safety Profile
The frequency and severity of treatment-emergent adverse events were similar between both study arms. Four serious infections occurred during the trial, with three in the pegcetacoplan group; however, none were attributed to encapsulated bacteria. One death occurred in the pegcetacoplan arm due to COVID-19 pneumonia but was considered unrelated to the treatment.
According to Carla M. Nester, MD, the Jean E. Robillard Chair in Pediatric Nephrology and the director of the Pediatric Glomerular Disease Clinic at the University of Iowa, "The results were consistent across patients with different characteristics. In addition, pegcetacoplan demonstrated favorable safety across native and post-transplant populations."
