Key Takeaways

• At the American Society of Retina Specialists (ASRS) 2024 Annual Meeting, researchers from around the world presented results from clinical studies aiming at reducing the burden of AMD treatment.
• Studies addressed identifying the best candidates for treatment, gene therapies that promise to reduce or eliminate need for injections and testing novel drugs with mechanisms of action that use different pathways than currently available medications.

Current treatments for age-related macular degeneration (AMD) have proven effective and safe. However, these lifelong therapies involve frequent eye injections. At the American Society of Retina Specialists (ASRS) 2024 Annual Meeting, researchers from around the world presented results from clinical studies aimed at reducing the burden of AMD treatment by:

• Identifying patients at a higher risk for degeneration and vision loss who will be more likely to respond to treatment
• Developing gene therapies that promise to drastically reduce or eliminate the need for injections
• Testing novel drugs with mechanisms of action that use different pathways than currently available medications, offering patients more options and longer-lasting treatments

Who to Treat

Anti–vascular endothelial growth factor (anti-VEGF) therapies shook the wet AMD treatment scene when they were introduced in the early 2000s. However, patients with the advanced form of dry AMD involving geographic atrophy (GA) have had less luck. Pegcetacoplan and avacincaptad pegol, complement inhibitors that target the humoral arm of the immune system, represent the only US Food and Drug Administration (FDA)–approved treatments for GA. Unfortunately, these drugs slow the progression of the disease but do not restore vision; in fact, vision continues to decline. 

Researchers are therefore developing tools to help clinicians identify GA lesions that are more likely to grow and reach the fovea, part of the retina at the back of human eyes responsible for sharp, central vision, as these are the lesions most likely to cause vision loss. “Potential predictors of rapid growth rates guide us clinically and allow patients to make more informed decisions about whether to pursue treatments that require frequent interventions,” Lisa Olmos de Koo, MD, an ophthalmologist at the University of Washington Eye Institute at Harborview, Seattle, told Medscape Medical News.

The Promise of Gene Therapy

The one-and-done promise of gene therapy could rattle the field once again. Trials presented at ASRS24 showed a drastic reduction (from 85% to 95%) in the number of anti-VEGF and complement treatments needed following gene therapy injection, improving patient vision while relieving them from the stress of monthly injections. 

But researchers are still debating the optimal corticosteroid regimen that is required for reducing the inflammatory response associated with the administration of gene therapies, especially those that use viruses to introduce the genetic material. The main controversy is whether systemic immunosuppression is necessary or if local therapies, such as topical and eye injection administration, can suffice. Results presented at the meeting suggest that local therapies alone can be effective, potentially reducing the need for systemic immunosuppression.

Currently, gene therapy clinical trials are designed for patients who have failed standard therapy or require frequent injections. “Once we figure out possible long-term side effects and how to deal with inflammation, [gene therapy] could reach many more patients,” Olmos de Koo said.

New Approaches Enter Pipeline

While gene therapy brings excitement to the field, it might not be for everyone, experts agreed at ASRS24. New agents are being evaluated to offer a broader range of treatment options with longer-lasting efficacy. Results from early-phase trials presented at the meeting show favorable safety and efficacy signals, especially for geographic atrophy. “Finally, after a long time, we have a lot of exciting drugs for geographic atrophy in the pipeline that seem to be safe, with many studies also showing a functional outcome in addition to anatomical outcome,” Dimitra Skondra, MD, PhD told Medscape Medical News. Examples are AVD-104, a sialic acid–coated nanoparticle developed by Aviceda Therapeutics designed to target both arms of the immune system (current treatments just target the humoral arm), and ONL1204, a novel agent designed to inhibit the activation of a protein that is activated and upregulated in geographic atrophy and is implicated in multiple cell death and inflammatory pathways. “We need to be cautiously optimistic,” Skondra said. “Larger studies will tell us if these signals are real. But it’s a very exciting time. I’m happy to see different mechanisms of action besides the complement because we can attack the disease from multiple fronts.”

Edited by Miriam Kaplan, PhD

Source: Manuela Callari, August 1, 2024; see source article