Apellis Receives Negative Opinion for Pegcetacoplan for GA in the EU; Plans to Seek Re-Examination of Application

Apellis Pharmaceuticals announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has adopted a negative opinion on the marketing authorization application (MAA) of intravitreal pegcetacoplan for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD). As previously announced, this opinion was expected based on a negative trend vote following an oral explanation meeting in December 2023.

Apellis' Syfovre (pegcetacoplan) was approved by the FDA in February 2023 making it the first treatment cleared in the US for GA. That approval was based on results from the phase 3 OAKS and DERBY studies. However, in July, a notification from the ASRS Research and Safety in Therapeutics (ReST) Committee alerted members to rare cases of retinal vasculitis that occurred after the first injection of Syfovre. Apellis has since identified a potential cause of the rare events of retinal vasculitis, noting that 'internal structural variations' were identified in the specific 19-gauge by 1½ inch filter needle included in certain injection kits.

In an overview posted on the European Medicines Agency website last week, the CHMP stated the benefits of Syfovre did not outweigh the potential risks. 

"Although the studies showed that Syfovre slowed the growth of geographic atrophy lesions, this did not lead to clinically meaningful benefits for patients. It was noted that benefits of a treatment should impact patients’ everyday functioning, and this was not demonstrated in the studies. In terms of safety, regular injections into the eye carry a significant risk of adverse events, including the development of other forms of AMD or inflammation in the eye, that could further worsen vision. Therefore, the Agency’s opinion was that the benefits of Syfovre did not outweigh its risks and it recommended refusing marketing authorisation," the CHMP noted. 

Apellis said it plans to seek immediate re-examination of its application.

“We are very disappointed in this outcome on behalf of the millions of Europeans with GA who currently have no treatment options for this irreversible form of blindness,” Jeffrey Eisele, PhD, chief development officer, Apellis, said in a company news release. “We plan to promptly initiate the re-examination of our application and address CHMP questions, with the goal of bringing this first-ever potential treatment to the GA community in Europe.”

The MAA is based on results from the phase 3 OAKS and DERBY studies at 24 months, which were published in The Lancet. Treatment with both every-other-month and monthly pegcetacoplan reduced GA lesion growth with increasing treatment effects over time and showed a well-demonstrated safety profile, according to Apellis. Additionally, pegcetacoplan preserved visual function longer in multiple post hoc phase 3 analyses that have been presented at medical congresses.