FDA Approves First Ever Targeted C3 Therapy for PNH

The US Food and Drug Administration (FDA) has approved pegcetacoplan (EMPAVELI) for adults with paroxysmal nocturnal hemoglobinuria (PNH) who are treatment naïve and patients switching from the C5 inhibitors eculizumab (Soliris) and ravulizumab (Ultomiris).

The treatment, developed by Apellis Pharmaceuticals, represents the first and only targeted C3 therapy to garner FDA approval.

The Study

The approval is based on data from the head-to-head phase 3 PEGASUS study, in which the treatment demonstrated superiority in comparison with eculizumab for the change from baseline in hemoglobin level at week 16 with an adjusted mean increase of 3.84 g/dL of hemoglobin (P <0.0001).

Pegcetacoplan also met non-inferiority when compared to eculizumab for the endpoint of transfusion avoidance, with 85% of patients treated with the study drug deemed transfusion free over 16 weeks, compared to 15% of eculizumab-treated patients.

The Treatment

“EMPAVELI has the potential to improve the lives of patients with PNH by increasing hemoglobin and reducing blood transfusion requirements,” said Olga Frankfurt, M.D., PEGASUS study investigator and associate professor in the department of medicine, division of hematology and oncology, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, in a statement. “Through my work as an investigator on the PEGASUS study, I was excited to see EMPAVELI providing broad control of PNH."

The approval does come with a boxed warning from the FDA stating pegcetacoplan could increase the risk of meningococcal and other serious infections caused by encapsulated bacteria that could become rapidly life threatening or fatal if not identified or treated early.