ReviewAmerican journal of ophthalmology2024
Drug Approval for the Treatment of Geographic Atrophy: How We Got Here and Where We Need to Go.
Review in American journal of ophthalmology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
57 citing papers in PubMed, 1 synthesis or guideline pooled it.
- 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.Frontiers in pharmacology · 2024Pooled it
- Longitudinal Prediction of Retinal Sensitivity Based on Disease Progression Quantified From Optical Coherence Tomography in Geographic Atrophy.Investigative ophthalmology & visual science · 2026Trial
- Exploring Trial Endpoints in Geographic Atrophy Based on Localized Functional Changes in Microperimetry and AI-Quantified OCT Biomarkers.Investigative ophthalmology & visual science · 2026Trial
- Supramolecular Nrf2-activating peptide nanotherapeutics enable deep retinal penetration and RPE targeting for dry age-related macular degeneration.Materials today. Bio · 2026Article
- [Pioneering trials in ophthalmology-From clinical trials to guideline treatment].Die Ophthalmologie · 2026Article
- Insights into the modulation of age-related macular degeneration: Molecular and systems-level perspectives.Acta ophthalmologica · 2026Article
- αB-crystallin elastin-like polypeptides for sustained ocular drug delivery.Drug delivery and translational research · 2026Article
- A Novel Pixel-Based Spatial Modeling Framework for Mapping At-Risk Retina in Geographic Atrophy Progression.Ophthalmology science · 2026Article
- Phage Display as a Promising Platform for Peptide Drug Discovery.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Pharmacological Characterization of a Novel Complement C3 Inhibitor Antibody Fragment.Ophthalmology and therapy · 2026Article
- Association of Antibiotic Use and New-Onset ICD Coding of Geographic Atrophy.Investigative ophthalmology & visual science · 2026Article
- Deep Learning-Based Automated Segmentation and Quantification of the Ellipsoid Zone and the RPE-Bruch's Membrane Complex in Healthy Subjects and in Geographic Atrophy.Diagnostics (Basel, Switzerland) · 2026Article
- AAV NRF2 gene therapy preserves retinal structure and function in rodent models of oxidative damage.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Complement-Modulating Mechanisms of Ginkgo biloba Extract in Dry AMD: Insights From Molecular Docking and Dynamics Simulations.Translational vision science & technology · 2026Article
- Clinical characteristics and progression rates of geographic atrophy in an Asian population from Singapore.Eye (London, England) · 2026Article
- Complement Inhibition in Geographic Atrophy: Clinical Evidence for Pegcetacoplan and Avacincaptad Pegol.Cureus · 2026Review
- Targeting Neuroinflammation and Oxidative Stress to Slow Neurodegeneration in the Visual System.Journal of clinical medicine · 2026Review
- Simultaneous Segmentation of Geographic Atrophy in Longitudinally Acquired Fundus Autofluorescence Images.Ophthalmology science · 2026Article
- Automated OCT-tailored and same-visit biomarker-targeted microperimetry in geographic atrophy.Scientific reports · 2026Article
- Systemic inflammation triggers local complement production in the mouse retina and RPE.Journal of neuroinflammation · 2026Article
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
purposeTo discuss the clinical trial results leading to the US Food and Drug Administration (FDA) approval of anti-complement therapies for geographic atrophy (GA), perspectives on functional data from the GA clinical trials, and how lessons from the FDA approval may guide future directions for basic and clinical research in AMD.
designSelected literature review with analysis and perspective
methodsWe performed a targeted review of publicly available data from the clinical trials of pegcetacoplan and avacincaptad for the treatment of GA, as well as scientific literature on the natural history of GA and the genetics and basic science of complement in AMD.
resultsThe approval of pegcetacoplan and avacincaptad was based on an anatomic endpoint of a reduction in the rate of GA expansion over time. However, functional data from 2 phase 3 clinical trials for each drug demonstrated no visual benefit to patients in the treatment groups. Review of the genetics of AMD and the basic science of the role for complement in AMD provides only modest support for targeting complement as treatment for GA expansion, and alternative molecular targets for GA treatment are therefore discussed. Reasons for the disconnect between anatomic and functional outcomes in the clinical trials of anti-complement therapies are discussed, providing insight to guide the configuration of future clinical studies for GA.
conclusionAlthough avacincaptad and pegcetacoplan are our first FDA-approved treatments for GA, results from the clinical trials failed to show any functional improvement after 1 and 2 years, respectively, calling into question whether the drugs represent a "clinically relevant outcome." To improve the chances of more impactful therapies in the future, we provide basic-science rationale for pursuing non-complement targets; emphasize the importance of ongoing clinical research that more closely pins anatomic features of GA to functional outcomes; and provide suggestions for clinical endpoints for future clinical trials on GA.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.