What to Know About Syfovre and Izervay for Geographic Atrophy

by Michigan Retina-Vitreous Institute

By Reena Mukamal Feb. 18, 2024 for the American Academy of Ophthalmology

Two new drugs – Syfovre (pegcetacoplan) and Izervay (avacincaptad pegol) – were approved in 2023 for geographic atrophy, a potentially debilitating type of dry age-related macular degeneration (AMD). The disease affects about one million Americans and can lead to significant vision loss.

For years, patients in the early to intermediate stages of dry AMD had a single treatment option — AREDS2 vitamins — to help reduce the risk of progression to advanced AMD. The two new drugs have heightened hope among patients and ophthalmologists alike.

“These drugs represent a scientific step in the right direction. But while these new treatments can slow down the rate of progression of geographic atrophy by a small amount, they have not been shown to have any effect on vision,” said retina specialist and Academy member Rahul N. Khurana, MD. Worse, they may cause unwanted side effects. 

“It’s important to talk with your ophthalmologist about whether their benefits balanced against their treatment burden and safety risks make either of them a good fit for you,” Dr. Khurana said.

If you are considering either of these new drugs, here’s what you need to know.

How do Syfovre and Izervay work?

Geographic atrophy causes regions of cells in the retina to waste away and die resulting in a growing blind spot in the visual field. This makes it difficult to drive, read, and even recognize faces.

Syfovre (Apellis Pharmaceuticals) and Izervay (IVERIC Bio) are injected directly into the eye once per month, or every other month, on an ongoing basis. The drugs calm the immune response to partially prevent damage to retinal cells. The two drugs work similarly, but they target different immune molecules.

How effective are Syfovre and Izervay for geographic atrophy?

In clinical trials, patients received injections monthly or every other month for one year. The drugs showed that they could slow the development of geographic atrophy by about 14% to 20%. Importantly, neither drug has demonstrated the ability to improve eyesight or restore lost vision.

These small improvements should be weighed against the burden of getting monthly injections for an indefinite amount of time – as well as the risk of side effects, some of which can be quite severe, said Dr. Khurana.

Risks and side effects of Syfovre and Izervay

Injections of both Syfovre and Izervay can cause inflammation, bleeding beneath the clear lining of the eye, blurred vision, and a temporary increase in fluid pressure in the eye.

Some patients developed a separate type of macular degeneration, called wet AMD, after taking the drugs. Wet AMD can also lead to vision loss and requires treatment with eye injections of anti-VEGF medication.

Even more concerning, both drugs have had reports of retinal vasculitis, an inflammation that blocks blood flow to the retina and can lead to irreversible blindness. A recent report from the American Society of Retina Specialists and other industry experts described 13 patients that developed this severe complication, including two who needed to have an eye removed.

Apellis, manufacturer of Syfovre, said that the drug’s safety in the real world is similar to what was reported in the clinical trials. The company says the risk of this rare complication is very low, at 0.01% per injection.

But that may not be an accurate number, said Dr. Khurana, explaining that the people who developed retinal vasculitis did so after their first injection.

“It may be more accurate to look at [how frequently this complication happens after] first-time injections rather than among the overall number of injections,” Dr. Khurana said. In either case, “the community is concerned because the inflammation rates are higher and more severe than what we saw in clinical trials.”

Bottom line: Communicate closely with your ophthalmologist

Between heavy celebrity marketing with spokesperson Henry Winkler and the lack of any other treatment for geographic atrophy, patient interest in both Syfovre and Izervay remains high. It’s important to talk with your ophthalmologist about the risks and benefits of these drugs, based on your own personal health history.

If you are being treated with Syfovre and Izervay and experience any of the following side effects, call your ophthalmologist immediately: