FDA-approved treatments for geographic atrophy help patients and open the door for future research
By Leah Sherwood
In the past, geographic atrophy (GA), the advanced stage of dry age-related macular degeneration (AMD), left both patients and retina specialists without treatment options. Characterized by a slow, relentless loss of vision, it progresses through the gradual degeneration of retinal cells, leading to permanent central visual acuity loss and significantly impacting daily activities such as reading and recognizing faces.
However, in February 2023, the US Food and Drug Administration approved pegcetacoplan (Syfovre®) for the treatment of GA.1 This approval was followed by that of avacincaptad pegol (Izervay™) in August 2023.2
Both pegcetacoplan and avacincaptad pegol are complement inhibitors, targeting key drivers of inflammation and cell death in GA, with the goal of slowing disease progression and preserving vision in patients with GA.3
“The FDA-approved complement inhibitors are the first treatments for the late form of dry AMD—GA—that, until now, had no treatment,” said Peter K. Kaiser, MD, a professor of ophthalmology at the Cole Eye Institute and the Case Western Reserve School of Medicine in Cleveland, Ohio. “GA is a relentlessly progressive disease that we, as retina specialists, watched helplessly the march toward loss of vision in our patients. We now have a way to slow this march.”
Part of the reason it has taken so long to identify a therapy for dry AMD is the lack of suitable animal models for research,4,5 Mitul Mehta, MD, MS, a clinical associate professor of ophthalmology at the University of California, Irvine, explained. Dry AMD primarily affects older individuals, but commonly used animal models like mice or primates were not suitable for studying this disease.
“One of the big problems from the research side of it was that there’s no animal model because animals don’t live long enough to develop AMD—for the most part. Certainly not primates, and mice don’t have maculas,” Dr. Mehta said.
Another issue was the emergence of the “blockbuster” anti-VEGF drugs for wet AMD, which is more acute and sudden in onset compared with dry AMD, according to Dr. Mehta.
“For years, dry AMD took a backseat to wet AMD because there were no treatments,” Dr. Mehta said. “Now, with these approvals, the field is finally getting the attention it deserves.”
The approval of complement inhibitors has also had an impact on retinal research more broadly. “It’s dramatically increased funding and interest in this area,” Dr. Kaiser said. “We’re seeing more innovation and collaboration than ever before.”
Dr. Mehta echoed this sentiment, noting the significance of these therapies after decades of stagnation.
“This is a major step forward,” he said. “We finally have tools to intervene and slow the progression of this disease. It’s not a cure, and it doesn’t restore vision, but it’s a critical starting point.”
Managing Patient Expectations
Despite these advances, clinicians need to clearly communicate to patients about the limitations of current treatments, Dr. Mehta noted.
“Our goal is to maximize your visual acuity and your ability to do things you want to do,” Dr. Mehta said.
Dr. Kaiser said that in his own practice, he uses serial OCT imaging to illustrate the progressive nature of GA to his patients.
“The progressive nature is easy for patients to understand as they notice the slow change in vision over time,” he said. “What starts as missing letters while reading progresses to larger and larger areas of missing vision. I show the progression on serial OCT images to illustrate the progressive nature in their own eyes.”
Dr. Mehta, who serves as the co-founder and chief medical officer at Eyedaptic, has been at the forefront of adaptive technologies, such as augmented reality glasses, to help patients with GA maintain their independence as their disease progresses.
“These glasses can improve vision by several lines on an eye chart,” he explained. “It’s not just about slowing the disease; it’s about helping people live better, more independent lives.”
Barriers to Access
Dr. Mehta pointed out that the demographics of the disease and the method of delivery of the available treatments can create barriers to access for patients.
“GA predominantly affects older adults, many of whom already face mobility and health issues,” he said. “For some patients, the logistics of getting to and from appointments are a major hurdle.”
This challenge is further compounded by the frequency of the required injections, Dr. Kaiser noted.
“The fixed and frequent need for injections is very difficult for patients and their caregivers,” he said. “It’s a significant commitment, and not everyone is willing or able to adhere to the treatment schedule. This is the hardest part—to continue the therapy and slow the progressive loss of vision. It is a hard concept for patients to understand that they are better off with the injections than they would have been. It is our job to reinforce this idea.”
In addition to their frequency, the location of the injections adds to the patients’ concerns, at least at first, according to Dr. Mehta.
“Right now, you have to inject a needle into the eye,” he said. “I try to make it comfortable for them.”
Addressing these barriers to access will require innovation in drug delivery methods, Dr. Mehta noted.
“There’s hope that future treatments might involve less frequent dosing or even noninvasive options like eye drops or oral medications,” he said.
Dr. Mehta noted that there are approximately 40 companies working on therapies to treat dry AMD currently, some of which will hopefully treat the disease before it affects the central vision. He added, “That’s the goal, right? To prevent it from affecting the central vision.”
Opening the Door to Innovation
There is significant potential to enhance the effectiveness of current treatments, Dr. Kaiser said, such as “a treatment that slows progression at a rate better than the 20% we see with the current FDA-approved complement inhibitors.”
According to Dr. Kaiser, the FDA regulatory approvals have jump-started therapeutic advancements in the field.
“The FDA’s approval of these therapies has opened the door for innovation in the dry AMD space,” Dr. Kaiser said. “We’re now seeing advancements in areas like lipid metabolism, other complement pathway targets, neuroprotection, oxidative stress reduction, and even optogenetics. Many of these approaches are already in phase 3 trials.”
Gene therapy is the therapeutic area Dr. Mehta is most excited about, but he acknowledges its limitations.
“The only issue is that the genetic target is not obvious, because it’s not very clear [that a] gene causes macular degeneration,” he explained.
Another promising area, Dr. Mehta added, is artificial intelligence (AI).
“AI is helping us analyze genetic data and identify new therapeutic targets,” he said. “It’s a powerful tool that could accelerate the development of more effective treatments.”
Leah Sherwood is a science writer in Los Angeles.
References
- FDA approves SYFOVRE™ (pegcetacoplan injection) as the first and only treatment for geographic atrophy (GA), a leading cause of blindness. Apellis. February 17, 2023. Accessed February 2, 2025. https://investors.apellis.com/news-releases/news-release-details/fda-approves-syfovretm-pegcetacoplan-injection-first-and-only?utm_source=chatgpt.com
- Iveric Bio receives U.S. FDA approval for IZERVAY™ (avacincaptad pegol intravitreal solution), a new treatment for geographic atrophy. Astellas. August 8, 2023. Accessed February 2, 2025. https://www.astellas.com/en/news/28281
- Wang H, Zheng J, Zhang Q, et al. Efficacy and safety of complement inhibitors in patients with geographic atrophy associated with age-related macular degeneration: a network meta-analysis of randomized controlled trials. Front Pharmacol. 2024;15:1410172. doi:10.3389/fphar.2024.1410172
- Pennesi ME, Neuringer M, Courtney RJ. Animal models of age-related macular degeneration. Mol Aspects Med. 2012;33(4):487-509. doi:10.1016/j.mam.2012.06.003
- Ramkumar HL, Zhang J, Chan CC. Retinal ultrastructure of murine models of dry age-related macular degeneration (AMD). Prog Retin Eye Res. 2010;29(3):169-90. doi:10.1016/j.preteyeres.2010.02.002
