ASRS: Six Cases of Occlusive Retinal Vasculitis Reported After Injection of Apellis’ GA Drug Syfovre

Rare cases of retinal vasculitis have occurred after the first injection of Apellis Pharamceuticals’ recently approved geographic atrophy drug Syfovre (pegcetacoplan injection), according to a notification from the ASRS Research and Safety in Therapeutics (ReST) Committee. The safety concerns, posted online to ASRS members, caused Apellis’s shares to lose about half their value, just 5 months after the targeted C3 therapy became the first FDA approved treatment for GA.

In a notification dated July 15, the ASRS ReST Committee stated that it has received physician reports of intraocular inflammation (IOI) following administration of Syfovre. In addition to cases of mild-moderate IOI, these reports have also included cases of severe IOI, retinal vasculitis, and occlusive retinal vasculitis. To date, the ASRS has received 6 cases of occlusive retinal vasculitis. All events were observed after the first injection of Syfovre, between 7-13 days after drug administration, and with no specific lots implicated.

“The etiology of these events is unclear, and outcomes in these patients are still evolving,” according to the ASRS notification.

In an 8-K form filed with the SEC, Apellis stated that “Upon review with external experts, two of the events were confirmed as occlusive, one was confirmed as non-occlusive, and the remaining three were undetermined based on limited information and lack of imaging.”

In the pivotal phase 3 DERBY and OAKS trials, intraocular inflammation was noted in 2.1% (every other month) to 3.8% (monthly) of Syfovre patients at 24 months. The IOI cases from the trials included 4 cases of infectious endophthalmitis and 4 cases of severe intraocular inflammation, but no cases of retinal vasculitis. Apellis reviewed images and clinical data from all cases of IOI from their clinical trials and no cases of retinal vasculitis were found on secondary review of those patients, ASRS noted.

In a statement to Eyewire+, Apellis said that following the approval in February, the overall real-world safety profile of Syfovre has been consistent with clinical studies.

“There have been rare events of intraocular inflammation (IOI) with retinal vasculitis reported in the real world at an estimated rate of approximately 0.01% per injection. Patient safety is our top priority, and we take any adverse event seriously,” Apellis stated. “All reported events were observed in real-world use between 7-13 days after the first injection. No cases of retinal vasculitis were reported in the pivotal phase 3 studies of Syfovre. We are in the process of thoroughly investigating all cases with external experts, including real-world procedure technique and potential risk factors.”

According to Apellis, about 60,000 vials of Syfovre has been distributed since the February 17, 2023 FDA approval.

In the ASRS note, Apellis stated it is working closely with the ReST committee to follow these cases and plans to keep the retina community updated with available information.

Practioners can report adverse events by clicking on the ASRS found here.