Details on 5 Cases of Complications From Syfovre Injections | AAO 2023

The Wolfe Eye Clinic in Iowa paused use of Syfovre (pegcetacoplan), the recently approved treatment for geographic atrophy, after five patients developed complications that halted further treatment with the drug, according to a presentation one of its retina specialists gave at the annual meeting of American Academy of Ophthalmology (AAO) in San Francisco.

One of the patients experienced hemorrhagic occlusive vasculitis-type inflammation and continues to have no light perception — clinical terminology for blindness — in the treated eye, reported William J. Johnson, M.D., a retinal fellow at the Wolfe Eye Clinic, which has 24 locations in Iowa.

Johnson, who spoke Friday during a session on devoted to late-breaking research, said Wolfe Clinic retina specialists administered 129 injections of Syfovre in 96 eyes of 84 patients between March 2023 and mid-July 2023, when it paused the use of Syfovre injections because of the complications.

“The retina division of the Wolfe Eye Clinic administers 65,000 injections annually and has participated in 18 clinical trials related to geographic atrophy and this was atypical compared to our collective experience,” said Johnson.

The FDA approved Syfovre in February 2023, and it hit the market shortly afterward as the first FDA-approved drug for geographic atrophy, an advanced form of “dry” age-related macular degeneration that can cause blindness.

Safety concerns about Syfovre surfaced in July 2023 when a research and safety committee of the American Society of Retina Specialists issued a warning about six cases of retinal vasculitis. Two of the cases that Johnson discussed at the AAO meeting were among those six. The drug’s maker, Apellis Pharmaceutical, issued a press release approximately two weeks later about seven cases and possibly another.

In early October 2023,members of a retina specialist group in Northern California reported in the journal JAMA Ophthalmology that 16 (29%) of the 55 patients that hey had treated with Syfovre had developed floaters.

Related: Floaters Are a Common Side Effect of Syfovre, A New Treatment for Geographic Atrophy, Case Series Finds

Here are some of the details of the five cases Johnson presented at the AAO meeting. He provided a few more details in a subsequent phone conversation:

• An 80-year-old man who developed silicone oil droplet complications experienced symptomatic floaters. There was no objective change in vision or inflammation, but the patient decided not to have any further treatments. Other patients have experienced silicone oil droplet complications but not with floaters that caused them to stop treatment.
• A 72-year-old woman developed intermediate and anterior (front of the eye) uveitis following her first injection with Syfovre. Her vision returned to its baseline level after intensive topical steroid treatment.
• An 86-year-old woman developed uveitis after her second Syfovre injection. Her condition improved initially with steroid drops but then worsened. She was treated with antibiotics and steroid injections in the eye but did not improve. After more intense steroid treatment was started, her vision slowly improved over 10 weeks and returned to being just below baseline. Johnson said there was some debate about how this case should be classified, with Wolfe specialists seeing some findings as evidence pointing to preexisting branch retinal vein occlusion but others seeing them as evidence of hemorrhagic vasculitis without occlusion.
• A 72-year-old woman presented with vision loss seven weeks after a Syfovre injection. Her vision improved after three monthly treatments with Vabysmo (faricimab), an anti-vascular endothelial growth factor (VEGF) used to treat neovascular, or wet, AMD. She had converted from dry to wet AMD, and Johnson said such cases were seen in clinical trials of Syfovre and are a known complication. Her vision improved with the Vabysmo treatments but never fully recovered and remained below her baseline level.

The fifth case was the patient who experience no light perception in his treated eye. Johnson said he was a 96-year-old man who presented nine days after his first injection with decreased vision, pain, elevated pressure in the eye, and vasculitis. He was initially treated with antibiotics, steroids and topical eye hypertensives. That treatment was followed by stronger steroids and then by anti-VEGF therapy. Johnson said the baseline vision of the treated eye was 20/60.

In his concluding remarks, Johnson shifted gears from the granularity of the individual cases to advise takng a cautious approach when prescribing new medications.

“The allure of novel therapies for diseases with significant morbidity can be immense for both patients and physicians and this [geographic atrophy] remains a severe disease for which arrest[ing] progression would be ideal,” he said

Johnson added: “Because modern trials seem unlikely or unable to elucidate all complications, it seems that there’s some prudence in presenting novel therapies that are recently approved with caution given the uncertainty related to emergent side effects.”

Johnson also noted the difference between the anti-VEGF therapy and Syfovre and another recently approved for geographic atrophy treatment, Izervay (avacincaptad pegol), which like Syfovre inhibits complement, a branch of the immune system that seems to play a role in causing geographic atrophy. Anti-VEGF is likely to preserve vision now with the risks coming later, he said, whereas complement inhibition may provide benefit later, but the risks appear to occur in the period soon after treatment, he said.