Rare Daily Staff

The U.S. Food and Drug Administration approved Apellis Pharmaceuticals’ Empaveli, the first and only targeted C3 therapy, for treatment of adults with paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, chronic, life-threatening blood disorder caused by an acquired mutation, which leads to uncontrolled complement activation and the destruction of red blood cells through intravascular and extravascular hemolysis. According to a retrospective and a cross-sectional study of patients treated with C5 inhibitors, at least 72 percent had persistently low hemoglobin and at least 36 percent required one or more transfusions a year.

Empaveli is approved for use in adults with PNH, who are treatment naïve as well as patients switching from Alexion Pharmaceuticals’ the C5 inhibitors Soliris and Ultomiris, the current standard of care.

“This approval represents a major scientific advancement as Empaveli ushers in the first new class of complement medicine in almost 15 years,” said Cedric Francois, co-founder and CEO, Apellis. “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.”

The approval also puts Apellis in direct competition with powerhouse rare disease pharmaceutical Alexion, which was recently acquired by AstraZeneca.

The approval of Empaveli is based on results from the head-to-head phase 3 PEGASUS study, which were recently published in the New England Journal of Medicine. In the PEGASUS study, Empaveli met the primary endpoint, demonstrating superiority to Soliris 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). Additionally, Empaveli met non-inferiority compared to Soliris on the endpoint of transfusion avoidance. Eighty five percent of Empaveli-treated patients were transfusion free over 16 weeks versus 15 percent of Soliris-treated patients.

“We are pleased to hear of the FDA’s decision to approve Empaveli, which is an important milestone for patients,” said Janice Frey-Angel, chief executive officer and executive director, Aplastic Anemia and MDS International Foundation. “Many PNH patients are seeking choices in their treatment, so the approval brings new promise for the PNH community.”

Empaveli (pegcetacoplan) is the first and only approved therapy targeting C3, the central protein in the complement cascade. The drug acts proximally in the complement cascade controlling both C3b-mediated extravascular hemolysis and terminal complement-mediated intravascular hemolysis.

The approval of Empaveli carries a boxed warning that it 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 approved by the FDA for Empaveli. Prescribers 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 reaction in patients treated with Empaveli was infections (5 percent). The most common adverse reactions with Empaveli were injection site reactions (39 percent), infections (29 percent), diarrhea (22 percent), abdominal pain (20 percent), respiratory tract infection (15 percent), viral infection (12 percent), and fatigue (12 percent). No cases of meningitis and no deaths were reported in patients treated with Empaveli.

Apellis plans to price the drug at $458,000 per year, a price in line with the annual cost of Ultimoris, its main competitor. Alexion says it has moved at about three quarters of its patients to Ultimoris, as Soliris is set to lose patent protection in two years. The drug is under review by the European Medicines Agency with the potential for a European Commission decision in the second half of 2021.

In October 2020, Apellis and Sobi entered a collaboration to develop and commercialize systemic pegcetacoplan. The companies have global co-development rights for systemic pegcetacoplan, with Apellis retaining exclusive U.S. commercialization rights and worldwide commercial rights for ophthalmological pegcetacoplan, including for geographic atrophy (GA). Sobi has exclusive ex-U.S. commercialization rights for systemic pegcetacoplan.

Photo: Cedric Francois, co-founder and CEO, Apellis

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