FDA Approves Empaveli for Two Rare Kidney Diseases

The FDA has approved a new indication for Empaveli (pegcetacoplan) injection to treat adults and children aged 12 years and older with C3 glomerulopathy (C3G) or primary immune-complex membranoproliferative glomerulonephritis (IC-MPGN), two rare kidney diseases that can cause kidney failure.

This will be the first medication approved for children with C3G and the first medication approved for the treatment of adults and children with primary IC-MPGN.

These two diseases are caused by abnormal overactivity of the complement system, a part of the immune system, leading to buildup of immune deposits in the glomeruli, the parts of the kidneys that filter out waste and excess water. These deposits can cause kidney inflammation and damage. Approximately one-half of patients with C3G and primary IC-MPGN develop kidney failure within five to 10 years of diagnosis, requiring a kidney transplant or lifelong dialysis. The diseases are estimated to affect 5,000 people in the United States and up to 8,000 in Europe.

Carla Nester, M.D.

“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,” Carla Nester, M.D., lead principal investigator for the VALIANT study, professor of internal medicine and pediatrics and director of pediatric nephrology at the University of Iowa Stead Family Children's Hospital, said in a news release.

Developed by Apellis Pharmaceuticals, Empaveli works by inhibiting part of the complement system. It is a targeted C3 therapy designed to regulate excessive activation of the complement cascade, part of the body’s immune system, which can lead to the onset and progression of many serious diseases.

Empaveli is already approved to treat adults with paroxysmal nocturnal hemoglobinuria (PNH), an acquired blood disorder that can destroy the complement system. This can lead to the destruction of red blood cells within blood vessels, the spleen, and the liver, as well as blood clots and anemia. The list price is about $505,000 per year, according to a company spokesperson. Apellis offers a trial of 8 weeks of Empaveli at no cost, as well as a copay program for commercially insured patients and a patient assistance program.

The FDA’s new approval in kidney diseases is based on results from the phase 3 VALIANT study, in which Empaveli demonstrated a 68% reduction in proteinuria (an abnormal amount of protein in the urine), stabilization of kidney function, and substantial clearance of C3 deposits as measured by C3 staining, compared with 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.

In this trial, 124 patients 12 years and older were randomly assigned to Empaveli or placebo administered twice weekly as a subcutaneous (under the skin) infusion for 26 weeks. After the 26 weeks, patients were able to participate in an open-label study for another 26 weeks. The most common adverse reactions in the VALIANT study were infusion site reactions, pyrexia, nasopharyngitis, influenza, cough, and nausea.

Empaveli is available only through a restricted program under a REMS program because of the risk of serious infections caused by encapsulated bacteria. Patients considering treatment with Empaveli are required to be vaccinated against infections caused by encapsulated bacteria (Streptococcus pneumoniae and Neisseria meningitidis serogroups A, C, W, Y, and B), according to current Advisory Committee on Immunization Practices (ACIP) recommendations. Empaveli can increase the risk of these infections.