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AAO 2024: Geographic Atrophy Breakthroughs or Bust?

The spotlight was on geographic atrophy (GA) at the co-sponsored Macula Society symposium on Day 3 of the 128th Annual Meeting of the American Academy of Ophthalmology (AAO 2024), as some of the brightest minds in retina gathered to dissect the latest FDA-approved breakthroughs in reducing disease progression.

If you’ve been keeping an eye on the news in ophthalmology, you know that the once bleak outlook for GA—an advanced form of age-related macular degeneration (AMD)—has taken a turn with the arrival of two new therapies—pegcetacoplan (Syfovre; Apellis Pharmaceuticals, Waltham, USA) and avacincaptad (Izervay™; Astellas Pharma, Northbrook, USA). However, whispers of adverse events following pegcetacoplan treatment, such as choroidal neovascularization (CNV), endophthalmitis and retinal detachment, have cast a shadow over their excitement. Are the benefits of these drugs worth the risk?1 

During the session’s lively panel discussion, Dr. Judy Kim (USA) moderated a no-holds-barred conversation between a group of experts who shared their experiences, opinions and—unsurprisingly—some sharp disagreements over the clinical utility of these treatments.

Dr. David Brown (USA) was one of the more enthusiastic proponents of the new drugs. “We’ve been doing research on geographic atrophy for 15 years, and we’ve never found anything to slow it down,” he said. He made it clear that while these drugs aren’t perfect, they offer patients something they’ve never had before: the possibility of slowing the disease. “They don’t stop it, they don’t reverse it, but they slow it down,” he added with a kind of pragmatic optimism. For him, the pitch to patients is simple: protect as much vision as possible, even if central visual acuity isn’t affected right away.

But not everyone on the panel shared Dr. Brown’s perspective. Dr. Richard Spaide (USA) was more skeptical, challenging the enthusiasm with his signature dry wit. “The argument for using the drug is that your relative growth rates would be slower,” he began to explain. “If Dan Martin got 5% interest and I got 4%, he’d brag about getting 25% more interest,” likening the supposed benefits of the drugs to comparing marginally different interest rates in bank accounts. 

Dr. Daniel Martin (USA), meanwhile, summed up his reasons for avoiding the treatments in most cases. “The cost-benefit analysis just hasn’t made sense. You do the math—it’ll take almost five years before you’d see a meaningful difference for a typical patient with extrafoveal disease,” he explained. And when presented with the data on efficacy, “most patients are not interested.”

While Dr. Martin and Dr. Spaide stood firm in their reluctance, others like Dr. Clement Chan (USA), who reported rarely using the drugs, described situations where these therapies might still be valuable. “In a clinical setting, when you have a patient that’s already lost severe vision in one eye due to GA and the other eye is approaching the center, they are desperate,” he said, emphasizing that in those cases, any hope of slowing progression, however small, could be worth it.

The conversation took a financial turn when Dr. Spaide suggested, somewhat cheekily, that reimbursement might drive the use of these drugs more than their clinical impact. “You get paid money to do it. And if you give a lot of it, you get a rebate. That’s pretty substantial,” he noted, drawing some laughs—but also a serious rebuttal from Dr. Brown. “There’s some economics, but not much. You don’t get paid for the AC tap. You don’t get paid for the bilateral, for the 50%…is there enough economic benefit to use a drug that I think is not effective? Absolutely not,” he countered, shutting down the suggestion that economic incentives were a major factor.

Throughout the discussion, one thing became clear: there’s no one-size-fits-all approach to treating GA. Dr. Glenn Jaffe (USA), who rarely prescribes these therapies, brought up an important nuance, noting that patients who progress quickly might be better candidates. “If we know someone’s going to progress very quickly, that’s someone I might consider treating,” he said, emphasizing the importance of monitoring growth rates. 

Despite their differences, all panelists agreed on one thing: the need for better ways to monitor and manage GA progression in a real-world setting. Dr. Chan summed it up best: “We’re still in the dark ages of how to monitor this… I think we need to have surrogate measurements… From an anatomical standpoint, maybe AI can help us, because we can’t do all those fine measurements as far as growth rate in the clinical setting.”

Then Dr. Kim presented the panelists with a scenario. If today, one of their eyes has already gone, and their other eye is showing signs of GA, would they choose to treat it with one of these new injections? “Yes. I’m in the clinic with Charlie Wykoff every Wednesday. I’d let him check me on Wednesday afternoon after I see my patient,” Dr. Brown answered enthusiastically. Dr. Martin, however, declined, “I’ll take AREDS…It’s a no for me.”

As the session wrapped up, it was clear that while the therapies available today are a step forward, the journey toward effective treatment for GA is far from over. For now, it’s a game of small wins, close monitoring, and, as Dr. Brown put it, a bit of a “terrible sales pitch.” But hey, even in the retina, some progress is better than none.

Editor’s Note: Reporting for this story took place during the 128th Annual Meeting of the American Academy of Ophthalmology (AAO 2024) from 18-21 October in Chicago, Illinois, USA.

Reference

  1. Minaker S, MacCumber MW, Pieramici DJ, et al. Real-world practice patterns and adverse events of pegcetacoplan injection for geographic atrophy. IOVS. 2024;65(7):2793.
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