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Current and Future Therapeutic Agents for Geographic Atrophy and Practical Considerations for Retinal Specialists
TAKE-HOME MESSAGE
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In this review, the authors highlighted the landscape of current and future therapies for the treatment of patients with geographic atrophy (GA) from age-related macular degeneration (AMD). Current therapies, such as the intravitreal pegcetacoplan injection, target the complement cascade to reduce the inflammatory mediators implicated in GA development; it has been shown to reduce GA progression by 19% to 22% when dosed monthly. Future therapies include oral complement mediator inhibitors, such as danicopan; intravitreal gene therapies, which reduce membrane attack complex activity and cell death; and novel injectable proteins, which directly inhibit immune cell activity.
- Ophthalmologists and those caring for patients with GA from AMD may benefit from a knowledge of therapies currently available and under future development.
abstract
This abstract is available on the publisher's site.
Access this abstract nowPURPOSE OF REVIEW
Geographic atrophy (GA) from age-related macular degeneration (AMD) remains a leading cause of vision loss. The purpose of this review is to summarize currently available intravitreal therapeutics, and discuss pipeline therapeutics that are currently in clinical trials.
RECENT FINDINGS
The FDA approval of pegcetacoplan and avacincaptad pegol, both approved in 2023, represent the first therapeutics to treat GA. These are delivered via intravitreal injections, and have been shown to slow progression of GA. Both drugs have a risk of new onset neovascular age-related macular degeneration (nAMD). Initial indications seem to be that pegcetacoplan therapy has higher risks of inflammation, vasculitis, and nonarteritic ischemic optic neuropathy (NAION) as compared to avacincaptad pegol, but more real-world data will help to clarify this further. Pipeline therapeutics that we discuss include intravitreal gene therapy, oral anticomplement therapy, and intravitreal injections of a novel glycoprotein.
SUMMARY
Both pegcetacoplan and avacincaptad pegol are FDA approved to treat GA. The decision to treat patients is still complex and nuanced, but the approval of two treatments for GA is a tremendous advance in our field. Future therapeutics may further refine our ability to treat patients more effectively and safely.
Additional Info
Disclosure statements are available on the authors' profiles:
Geographic atrophy: current and future therapeutic agents and practical considerations for retinal specialists
Curr Opin Ophthalmol 2024 May 01;35(3)165-169, P Vakharia, D EichenbaumFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Vakharia and Eichenbaum wrote a concise review introducing two new FDA-approved drugs for the treatment of patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD). These new medications, pegcetacoplan (a complement factor C3 inhibitor) and avacincaptad pegol (a complement factor C5 inhibitor), are aimed at slowing the progression of GA by regulating and inhibiting inflammatory reactions in the retina. The discovery of both drugs is a significant achievement in translational research, as preclinical studies have shown the critical role of complement activation in the recapitulation of AMD pathophysiology, which paved the way for the utilization of these medications in clinical practice.
For patients with GA, we can now offer some therapeutic options for the first time, even though these options may not be able to stop or reverse GA progression. Notably, these new treatments are not suitable for all patients with GA, as there may be multiple subtypes of AMD with different prognoses and underlying pathologic pathways. In order to administer these drugs to the right patient, clinically more specific diagnostic techniques, such as optical coherence tomography or optical coherence tomography angiography, which can identify GA subclassifications, would be required in future studies.