Apellis issues update on rare events associated with eye injection; cause still unknown

Apellis Pharmaceuticals says it has conducted a review of the rare but sight-threatening adverse events reported in real-world treatment with the company's newly approved pegcetacoplan injection for geographic atrophy — but can't seem to pinpoint a cause.

The drug in question, branded Syfovre, was approved by the FDA back in May, making it the first and only approved treatment for geographic atrophy (GA), a leading cause of blindness. GA is an advanced form of age-related macular degeneration. It is a progressive and irreversible disease caused by the growth of lesions, which destroy the retinal cells responsible for vision. By targeting C3, Apellis' Syfovre is designed to provide comprehensive control of the complement cascade, part of the body’s immune system.

Signs of trouble started in early July when the American Society of Retina Specialists (ASRS) received its first report of retinal vasculitis, an inflammation of the retinal vessels that could lead to blindness. Over the next week, the ASRS Research and Safety in Therapeutics (ReST) committee received six more reports. The committee contact Apellis and also released communication regarding the events to its members.

Apellis launched its own investigation, spearheaded by an internal safety committee and external retina/uveitis specialists. The Massachusetts-based biopharma confirmed seven events of retinal vasculitis (4 occlusive, 3 non-occlusive). Two of these events followed injections in April, two in May, and three in June.

The investigation included a review of the Syfovre manufacturing process and drug product quality, and the safety data from the company’s phase 3 clinical trials. Apellis found no indication that drug product or manufacturing issues contributed to the events, and no new safety findings in the clinical trials upon secondary review.

According to Apellis, as of July 29, 2023, more than 68,000 vials of Syfovre have been distributed since FDA approval, as well as 23,000 injections as part of clinical trials — making the reaction extremely rare. Nevertheless, Apellis says it will continue to work closely with the retina community and investigate potential contributing factors and plans to continue to provide updates.