Pegcetacoplan is a targeted C3 therapy that is intended to regulate excessive activation of the complement cascade.
New study findings from Sobi and Apellis Pharmaceuticals Inc announced positive topline results from the phase 3 VALIANT (NCT05067127) study that assessed systemic pegcetacoplan (Empaveli, Apellis Pharmaceuticals Inc) among individuals with C3 glomerulopathy (C3G) or primary immune complex membranoproliferative glomerulonephritis (IC-MPGN).1
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"Today's announcement further strengthens our belief in pegcetacoplan's potential to meet the critical needs of patients with these severe and life-threatening kidney conditions," Lydia Abad-Franch, MD, head of R&D of medical affairs and chief medical officer at Sobi, said in a news release. "We remain committed to progressing pegcetacoplan's development and expanding its reach, driven by our steadfast mission to transform the lives of those affected by rare diseases."1
C3G and primary IC-MPGN are kidney diseases that could result in kidney failure. The diseases effect nearly 5000 US individuals and around 50% of individuals with C3G and IC-MPGN experience kidney failure within the first 5 to 10 years of the diagnosis. Additionally, two-thirds of individuals that received a kidney transplant will face disease recurrence. Both diseases occur when the complement cascade is overactive which causes excessive breakdown of the C3 protein, leading to kidney inflammation, damage, and failure. Study authors noted that symptoms for C3G and IC-MPGN are similar, including blood in the urine, dark foamy urine caused by the presence of protein, edema, high blood pressure, and decreased urine output. However, there are no current treatments that aid the underlying cause of the diseases.1,2
Pegcetacoplan, a targeted C3 therapy could offer treatment to aid C3G and IC-MPGN as it is intended to regulate excessive activation of the complement cascade, according to study authors.1
"As a clinician, I'm thrilled by these groundbreaking results, which show that pegcetacoplan has the potential to significantly improve the lives of patients with C3G and IC-MPGN, regardless of disease type, age, and transplant status," Carla Nester, MD, MSA, FASN, lead principal investigator for the VALIANT study and Jean E. Robillard MD, professor of paediatric nephrology at the University of Iowa Stead Family Children's Hospital, said in a news release. "Currently, many patients living with these rare diseases will eventually require a kidney transplant or lifelong dialysis, so there is an urgent need for a treatment that targets the underlying cause of these diseases. These positive data are a major advance for the rare kidney disease community."1
The randomized, placebo controlled, double-blinded, multi-center VALIANT phase 3 study assessed the efficacy and safety of pegcetacoplan among 124 individuals 12 years and older with C3G or primary IC-MPGN. The study authors noted that the individuals were randomly assigned to receive 1080 mg of pegcetacoplan or a placebo twice weekly for 26 weeks. After the 26 weeks all individuals were permitted to receive pegcetacoplan.1
Trial Name: Phase III Study Assessing the Efficacy and Safety of Pegcetacoplan in Patients With C3 Glomerulopathy or Immune-Complex Membranoproliferative Glomerulonephritis (VALIANT)
ClinicalTrials.gov ID: NCT05067127
Sponsor: Apellis Pharmaceuticals Inc
Completion Date: December 2024
The study authors noted that the study met its primary endpoint, displaying a significant and clinically meaningful 68% proteinuria reduction in C3G and IC-MPGN among individuals that were treated with pegcetacoplan compared to the placebo as well as background therapy at 26 weeks. The secondary end point displayed at least 50% proteinuria reduction compared to baseline in addition to minimal significance on the histological endpoint of reduction in C3c staining on kidney biopsy and stabilization of kidney function as measured by stimated glomerular filtration rate compared to placebo, according to study authors.1
The positive results remained consistent across all subgroups, including adolescents and adult individuals withC3G and IC-MPGN, as well as individuals with native and post-transplant kidneys, according to study authors.1
According to the study authors, the safety and tolerability of pegcetacoplan observed in the VALIANT study was consistent to its established profile. Additionally, rates of adverse events (AEs) and serious AEs which lead to study drug discontinuation were similar among pegcetacoplan and the placebo.1
"These results exceeded our already high expectations. Pegcetacoplan is the first investigational therapy to show such a strong reduction in proteinuria in C3G and IC-MPGN with supportive data across multiple measures of disease activity," Jeffrey Eisele, PhD, chief development officer at Apellis, said in a news release. "Building on pegcetacoplan's approval in PNH, we look forward to sharing these data with the FDA and working quickly to bring this treatment to patients with these debilitating kidney diseases."1
