The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has reaffirmed its decision to deny marketing authorization for Apellis Pharmaceuticals' intravitreal pegcetacoplan (Syfovre) for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD). This decision follows a re-examination requested by Apellis after the initial negative opinion was issued in June 2024.
The CHMP's primary concern remains that while pegcetacoplan slows the growth of GA lesions, it does not demonstrate clinically meaningful benefits that impact patients' everyday functioning. The agency also raised concerns about the safety profile, noting the risk of adverse events associated with regular intravitreal injections, including potential worsening of vision.
Cedric Francois, MD, PhD, CEO and co-founder of Apellis, expressed disappointment with the decision, stating, "We are deeply disappointed by this outcome, which leaves millions of Europeans with GA without a treatment for this irreversible form of blindness." He also noted the broad support for pegcetacoplan from the European retina community and dissenting votes from some CHMP members.
Frank G. Holz, OAKS and DERBY study investigator and professor at the University of Bonn, Germany, echoed this sentiment, stating, "It is disappointing to know that we will not be able to provide access to this treatment to GA patients in the EU... The Phase 3 data for pegcetacoplan are clinically meaningful and showed the potential to make a difference for EU patients."
Clinical Significance and Context
Geographic atrophy is an advanced form of AMD and a leading cause of blindness, affecting over five million people worldwide. It is characterized by progressive and irreversible vision loss due to the growth of lesions that destroy retinal cells. Currently, there are limited treatment options available in Europe for GA.
Pegcetacoplan is designed to target C3, a protein of the complement system. In the United States, Syfovre (pegcetacoplan injection) is approved for the treatment of GA secondary to AMD. The FDA approval was based on Phase 3 clinical trials that demonstrated a reduction in the growth rate of GA lesions.
CHMP's Rationale
The CHMP acknowledged the unmet medical need for effective GA treatments in the EU. However, the agency concluded that the magnitude of Syfovre's effectiveness did not outweigh the potential risks associated with its use. The CHMP emphasized that a treatment's benefits should translate into tangible improvements in patients' daily lives, which they felt was not adequately demonstrated in the provided studies.
Apellis remains committed to expanding access to pegcetacoplan in the U.S. and other regions globally, focusing on serving unmet patient needs. The company will likely need to reassess its European strategy in light of this decision.
