FDA Approves Pegcetacoplan as First Treatment for Rare Kidney Diseases

The U.S. Food and Drug Administration (FDA) has granted approval for pegcetacoplan (Empaveli), a groundbreaking therapy developed by Apellis Pharmaceuticals, to treat patients aged 12 and older suffering from two severe and rare kidney diseases: C3 glomerulopathy (C3G) and primary immune complex membranoproliferative glomerulonephritis (IC-MPGN). This approval, announced on July 28, 2025, represents a significant advancement in the treatment options available for these debilitating conditions, which affect an estimated 5,000 individuals in the United States and up to 8,000 in Europe.

C3G and primary IC-MPGN are characterized by kidney inflammation and damage, often culminating in kidney failure. Approximately 50% of affected individuals progress to end-stage renal disease within 5 to 10 years of diagnosis, necessitating either kidney transplantation or lifelong dialysis. Furthermore, studies indicate that about 90% of kidney transplant recipients experience disease recurrence, underscoring the urgent need for effective treatment options (National Institute of Diabetes and Digestive and Kidney Diseases, 2023).

Pegcetacoplan functions by targeting excessive activation of the complement system, specifically the C3 complement component, which plays a crucial role in the immune response. By regulating this cascade, pegcetacoplan is designed to mitigate the kidney inflammation and damage associated with these diseases. The therapy was previously approved for treating paroxysmal nocturnal hemoglobinuria and is currently under investigation for additional rare diseases in the fields of hematology and nephrology.

The approval of pegcetacoplan was supported by the results of the phase 3 VALIANT trial, a randomized, placebo-controlled study involving 124 patients diagnosed with C3G or primary IC-MPGN. According to Dr. Carla Nester, MD, MSA, FASN, the lead principal investigator of the VALIANT trial and director of pediatric nephrology at the University of Iowa Stead Family Children's Hospital, the trial demonstrated a remarkable 68% reduction in urine protein to creatinine ratio (UPCR) in patients treated with pegcetacoplan compared to those receiving a placebo at the 26-week mark (Nester et al., 2025).

Patients in the pegcetacoplan group also showed stabilization of kidney function, measured by estimated glomerular filtration rate (eGFR), and significant reductions in C3c staining intensity, with 71% achieving complete clearance compared to the placebo group. Dr. Bradley P. Dixon, MD, FASH, a professor of pediatrics and medicine at the University of Colorado School of Medicine and a co-investigator of the VALIANT trial, highlighted that pegcetacoplan offers clinically meaningful benefits by addressing key markers of the disease (Dixon et al., 2025).

The FDA's approval of pegcetacoplan comes at a critical time for patients with these rare kidney diseases, providing much-needed hope for improved management and outcomes. The favorable safety profile of pegcetacoplan aligns with previously reported data, marking it as a potentially life-changing therapy for individuals affected by C3G and primary IC-MPGN.

As the medical community anticipates the broader implications of this approval, experts are optimistic about the future of treatment options for rare kidney diseases. The ongoing research and development in this area may pave the way for additional therapies that could further enhance patient care and outcomes in this vulnerable population.