FDA Approves Pegcetacoplan for Paroxysmal Nocturnal Hemoglobinuria

FDA

The FDA has approved pegcetacoplan (Empaveli) for the treatment of adults with paroxysmal nocturnal hemoglobinuria who are treatment naïve and those who are switching from the C5 inhibitors eculizumab (Soliris) and ravulizumab (Ultomiris).

The regulatory decision was based on data from the phase 3 PEGASUS study, where the agent met the primary end point of the trial when it demonstrated superiority to 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 <.0001). Moreover, pegcetacoplan was found to have noninferiority to eculizumab on the end point of transfusion avoidance. Specifically, 85% of patients who received pegcetacoplan were transfusion free over 16 weeks compared with 15% of those who received eculizumab.

“As the first, FDA-approved targeted C3 therapy, [pegcetacoplan] has the potential to redefine treatment for adults with PNH, including patients switching from any C5 inhibitor and treatment-naïve patients. Thank you to the clinical trial participants, PNH community, investigators, healthcare professionals, SFJ Pharmaceuticals, and more who helped contribute to this significant milestone,” Cedric Francois, MD, PhD, co-founder and chief executive officer, Apellis, stated in a press release. “This approval represents a major scientific advancement as [pegcetacoplan] ushers in the first new class of complement medicine in almost 15 years. We look forward to exploring the full potential of targeting C3 and continue to advance registrational programs of this therapy across multiple complement-driven diseases with high unmet need.”

Notably, the prescribing information for pegcetacoplan contains a boxed warning in that the agent may increase the risk of meningococcal and other serious infections caused by encapsulated bacteria that may become rapidly life threatening or fatal if not recognized and treated early.

A Risk Evaluation and Mitigation Strategy (REMS) has been given the green light by the regulatory agency for pegcetacoplan. As such, those prescribing the agent must counsel patients about the risk of serious infection, provide patients with the REMS educational materials, and ensure patients are vaccinated against encapsulated bacteria.

The most common serious adverse effect in patients treated with pegcetacoplan was infections (5%). The most common toxicities experienced with pegcetacoplan were injection site reactions (39%), infections (29%), diarrhea (22%), abdominal pain (20%), respiratory tract infection (15%), viral infection (12%), and fatigue (12%). No cases of meningitis and no deaths were reported in patients treated with pegcetacoplan.

Reference

Apellis announces US Food and Drug Administration (FDA) approval of EMPAVELI (pegcetacoplan) for adults with paroxysmal nocturnal hemoglobinuria (PNH). News release. Apellis Pharmaceuticals, Inc. May 14, 2021. Accessed May 14, 2021.