Apellis Pharmaceuticals, Inc. announced that the U.S. Food and Drug Administration (FDA) has approved EMPAVELI^® (pegcetacoplan) as the first treatment for C3 glomerulopathy (C3G) or primary immune complex membranoproliferative glomerulonephritis (IC-MPGN) in patients 12 years of age and older, to reduce proteinuria. C3G and primary IC-MPGN are rare kidney diseases, affecting 5,000 people in the United States.¹

“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, M.D., MSA, FASN, lead principal investigator for the VALIANT study, professor of internal medicine and pediatrics and director of pediatric nephrology, University of Iowa Stead Family Children's Hospital. “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.”

In the Phase 3 VALIANT study, EMPAVELI demonstrated an unprecedented 68% reduction in proteinuria, stabilization of kidney function, and substantial clearance of C3 deposits as measured by C3 staining, compared to placebo. The positive results were consistent across adolescent and adult patients with C3G and primary IC-MPGN, and in C3G patients with post-transplant disease recurrence.

“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. In the largest pivotal study of these diseases, EMPAVELI demonstrated its potential to preserve kidney function by controlling all three key markers of disease,” said Cedric Francois, M.D., Ph.D., co-founder and chief executive officer, Apellis. “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.”

“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, chief executive officer, NephCure. “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.”

The approval of EMPAVELI is based on positive six-month results from the VALIANT study, demonstrating benefits across all three key markers of disease:

• Proteinuria reduction: The study met its primary endpoint, demonstrating a statistically significant 68% (p<0.0001) proteinuria reduction in EMPAVELI-treated patients compared to placebo.
• Stabilization of kidney function: EMPAVELI-treated patients achieved stabilization of kidney function compared to placebo (nominal p=0.03) as measured by estimated glomerular filtration rate (eGFR).
• Reduction of C3 staining: A majority of EMPAVELI-treated patients achieved a reduction in C3 staining intensity (nominal p<0.0001) compared to placebo. 71% of EMPAVELI-treated patients achieved zero C3 staining intensity, demonstrating complete clearance of C3 deposits. 

The safety profile of EMPAVELI is well-established, with >2,200 patient years across all approved indications. The most common adverse reactions in the VALIANT study (≥10%) were infusion site reactions, pyrexia, nasopharyngitis, influenza, cough, and nausea.