Key Takeaways
- FDA Approval for Rare Kidney Diseases: Empaveli (pegcetacoplan) is now the first FDA-approved treatment for with C3 glomerulopathy (C3G) and primary immune complex membranoproliferative glomerulonephritis (IC-MPGN) in patients aged 12 years and older, marking a major milestone in nephrology care.
- Strong Clinical Results in VALIANT Trial: The Phase III VALIANT trial showed a 68% reduction in proteinuria, stabilization of kidney function and 71% complete clearance of C3 deposits with Empaveli treatment.
- High Unmet Need in C3G and IC-MPGN: These rare kidney diseases affect approximately 5,000 people in the United States and up to 8,000 in Europe, with high rates of progression to kidney failure and post-transplant recurrence.
The FDA has approved Apellis Pharmaceuticals’ Empaveli (pegcetacoplan) as the first treatment for C3 glomerulopathy (C3G) and primary immune complex membranoproliferative glomerulonephritis (IC-MPGN) in patients aged 12 years and older to reduce proteinuria. According to the company, the approval was based on six-month data from the Phase III VALIANT trial (NCT05067127), in which Empaveli demonstrated high rates of proteinuria reduction, stabilization of kidney function, and a significant reduction in C3 deposits.1
What did VALIANT Trial Results Show about Empaveli’s Efficacy?
“I’m excited to now have a highly effective therapy for a broad range of patients living with C3G and primary IC-MPGN,” said Carla Nester, MD, MSA, FASN, VALIANT trial lead principal investigator, professor of internal medicine and pediatrics, director of pediatric nephrology, University of Iowa Stead Family Children's Hospital, in a press release. “With standard of care, patients living with these rare and severe diseases frequently progress to kidney failure, necessitating lifelong dialysis and/or a kidney transplant. Given the urgent need, particularly in children, the approval of Empaveli marks a pivotal moment in the treatment of rare kidney diseases.”
VALIANT Trial Design and Endpoints
- The randomized, placebo-controlled, double-blinded, multi-center VALIANT trial evaluated the safety and efficacy of Empaveli in 124 patients with C3G or primary IC-MPGN.
- Patients were randomly assigned to receive Empaveli or placebo twice weekly for a duration of 26 weeks.
- At the end of the 26-week controlled period, patients were eligible to enter a 26-week open-label phase, during which all patients received Empaveli.
- The primary endpoint of the trial was the log transformed ratio of urine protein-to-creatinine ratio at week 26 compared to baseline.
- Key secondary endpoints included, but weren’t limited to, the proportion of patients who meet the criteria for achieving a stable or improved estimated glomerular filtration rate (eGFR), change from baseline in eGFR, and the proportion of patients with evaluable renal biopsies showing decreases in C3 staining on renal biopsy from baseline.1,2
Key Findings
- Results showed that the trial met its primary endpoint, with Empaveli achieving a statistically significant 68% reduction in proteinuria compared to placebo (p<0.0001), indicating strong efficacy in lowering protein levels in the urine.
- Patients treated with Empaveli experienced stabilization of kidney function, as measured by eGFR (nominal p=0.03).
- The treatment led to a significant reduction in C3 staining intensity, with 71% of patients showing complete clearance of C3 deposits (p<0.0001).
- Common adverse events included infusion site reactions, pyrexia, nasopharyngitis, influenza, cough, and nausea.
- According to Apellis, the safety profile of Empaveli is well established across multiple approved indications.1
Company and Advocacy Perspectives
“Empaveli has the potential to be truly transformational for patients with C3G and primary IC-MPGN, who until now have had very few treatment options,” said Cedric Francois, MD, PhD, co-founder, CEO, Apellis, in the press release. “Empaveli demonstrated its potential to preserve kidney function by controlling all three key markers of disease. In the largest pivotal study of these diseases. As Apellis’ third approval in four years, this milestone underscores the unique ability of targeting C3 to improve patients’ lives. We are deeply grateful to everyone who made this approval possible and look forward to building on this momentum as we advance pivotal studies of Empaveli in other rare kidney diseases.”
According to Apellis, an estimated 50% of people living with C3G and primary IC-MPGN will suffer from kidney failure within five to 10 years of diagnosis. Furthermore, around 90% of patients who have undergone a kidney transplant are expected to see the disease return. These conditions are estimated to impact about 5,000 individuals in the United States and as many as 8,000 across Europe.1
“The approval of Empaveli is a historic milestone for people living with C3G and primary IC-MPGN, many of whom are adolescents or young adults,” said Josh Tarnoff, CEO, NephCure, in the press release. “We recognize Apellis’ commitment to these patients and their families, and to the research and innovation that will bring this life-changing treatment into the hands of patients that need it most.”
References
FDA Approves Apellis’ EMPAVELI® (pegcetacoplan) as the First C3G and Primary IC-MPGN Treatment for Patients 12 and Older. Apellis. July 28, 2025. Accessed July 31, 2025. https://investors.apellis.com/news-releases/news-release-details/fda-approves-apellis-empavelir-pegcetacoplan-first-c3g-and
Phase III Study Assessing the Efficacy and Safety of Pegcetacoplan in Patients With C3 Glomerulopathy or Immune-Complex Membranoproliferative Glomerulonephritis (VALIANT). Clinicaltrials.gov. Accessed July 31, 2025. https://www.clinicaltrials.gov/study/NCT05067127
