The Syfovre Balancing Act. The Retinal Vasculitis Risk Is Real But Research Also Points to Benefits | ASRS 2024

Last year’s annual meeting of the American Society of Retina Specialists (ASRS) was rocked by news that a small but notable number of patients treated with Syfovre (pegacetacoplan), the first-ever, FDA-approved treatment for geographic atrophy, developed retinal vasculitis, a serious complication that can lead to severe, permanent vision loss. The ASRS Research and Safety in Therapeutics Committee provided an almost day-by-day timeline and details on what was then a handful of cases.

At this year’s ASRS meeting in Stockholm, Sweden, this week, Syfovre’s risks and benefits were still a featured topic but the sense of urgency mellowed into the calmer territory more typical of medical conferences: discrepant findings and differing emphasis on risk and benefits but also points of agreement.

The combined results of two real-world evidence studies presented Thursday put the risk of developing retinal vasculitis at about 1 in every 1,330 patients. David Eichenbaum, M.D., a retinal specialist at the Retina Vitreous Associates of Florida in southwest Florida, and a consultant and speaker for Apellis Pharmaceuticals, the marker of Syfovre, put the first at 1 in every 4,000 first injections.

Samuel Minaker, M.D., M.Sc.

“I think it's still a great interest, and so that's why we'll continue to do our real world study to look at this,” said Samuel Minaker, M.D., M.Sc., an assistant professor at the Rush University Medical Center in Chicago and a physician at th eIllinois Retina Associates, who presented findings about the retinal vasculitis from one of the real-world studies. But Minaker said he uses both Syfovre and its rival, Izervay (avacincaptad pegol), to treat geographic atrophy, noting that there might be a trade off with Syfovre being more effective but having more documented risks.

Practice patterns how vary, he said, with some retinal specialists treating patients with Syfovre and others electing not to and possibly referring patients to specialists who do. “Patients just need to be aware that something is available, but it requires some more nuanced discussion because of these additional risks,” he said in an interview after his presentation.

The organizers of the “expert panel” session on Syfovre — the meeting schedule used the generic name, pegcetacoplan, not the brand name, in the title — seemed conscious of striking a balance. Eichenbaum and Sunir J. Garg, M.D., a retina specialist at the Wills Eye Hospital in Philadelphia, presented data supporting Syfovre’s efficacy. Minaker and Janani Singaravelu, M.D., M.S. a vitreoretinal surgery fellow at the Retina Group of Washington, in the Washington, D.C., presented real-world study data that focused on the complications, particularly retinal vasculitis.

Eichenbaum presented data from an open-label extension study of Syfovre showing the efficacy of monthly and every-other-month injections of Syfovre relative to sham treatment. There’s been some debate about the strength of the evidence for Syfovre having a positive effect on vision. Eichenbaum shared results that showing monthly injections of Syfovre reducing the risk of severe visual impairment by 38% relative to the sham treatment although there was only a 12% difference for every-other-month injections. Severe visual impairment was defined as sustained reduction in sight, as measured by two standard eye chart exams (the ETDRS and Snellen charts) for four months or more or without recovery.

Eichenbaum did not present retinal vasculitis data in detail but said after a total of 250,000 injections, it appears that retinal vasculitis occurs after 1 in every 4,000 first injections. One of the points of agreement about Syfovre and retinal vasculitis is that the risk seems limited to the first injections of the drug. “Once patients make it past that first injection it is not something that they need to worry about,” said Minaker.

“As we see the pegcetacoplan risk profile stay stable, we are seeing the clinical utility of pegcetacoplan come into clearer focus,” Eichenbaum summed up for the ASRS audience.

Microperimetry is a test that measure people’s field of vision by asking them whether they can see spots of light. Garg presented data showing that patients who had been treated for 36 months with Syfovre scored better on prespecified microperimetry end points than those who had only been treated for 12 months. In the written summary of his presentation, he said this was the first time a treatment for geographic atrophy had shown a positive visual function benefit according to a prespecified end point.

Minaker’s presentation showed data pulled from the electronic medical records from Retinal Consultants of America, a nationwide group that includes 265 retina specialists and Mid Atlantic Retina, the retinal specialist group based at Wills to which Garg belongs. The review covered the period from Feb.1, 2023, through March 30, 2024 (the FDA approved Syfovre in February 2023). During that period 6,525 patients were treated Syfovre and 32,080 injections were administered. Minaker said it was the largest dataset on the experience with Syfovre so far,

Minaker’s results showed that treatment of 853 of the 8,987 (9.49%) eyes treated with Syfovre was halted during the period of his study. His tally of adverse events included 296 new cases of choroidal neovascularization; 29 cases of mild intraocular inflammation, which he said worked out to 0.4% of all treated patients; and four cases of retinal vasculitis, which Minaker calculated to be a 0.06% per patient risk.

Singaravelu’s study included 1,091 patients treated with Syfovre at the three retina specialist groups that make up the PRISM Vision Group between February 2023 to October 2023. Ocular hypertension (defined as increase in intraocular pressure greater than 10 mmHg from baseline) occurred in 76 patients (5.25%) and was the most common ocular adverse event seen, Singaravelu reported.

Five cases (0.34% of the 1.451 treated eyes) of intraocular inflammation occurred, three of which were anterior uveitis and one a mild nonocclusive case of retinal vasculitis that was treated with topical steroids. The fifth case developed into hemorrhagic occlusive retinal vasculitis nine days after the first injection of Syfovre. Eventually the affected eye was removed (enucleation).