Current drug and molecular therapies for the treatment of atrophic age-related macular degeneration: phase I to phase III clinical development

ABSTRACT

Introduction: Age-related macular degeneration (AMD) is the leading cause of vision loss among the elderly. Atrophic AMD, including early, intermediate and geographic atrophy (GA), accounts for ~90% of all cases. It is a multifactorial degeneration characterized by chronic inflammation, oxidative stress and aging components. Although no FDA-approved treatment yet exists for the late stage of atrophic AMD, multiple pathological mechanisms are partially known and several promising therapies are in various stages of development.

Areas covered: Underlying mechanisms that define atrophic AMD will help provide novel therapeutic targets that will address this largely unmet clinical need. The purpose of this paper is to review current promising drugs that are being evaluated in clinical trials. Because no pharmacological treatments are currently available for late stage of atrophic AMD, any new therapy would have extensive market potential.

Expert opinion: The number of AMD patients is predicted to increase to ~30 million worldwide by 2020. In response to this enormous unmet clinical need, new promising therapies are being developed and evaluated in clinical trials. We propose that the assessment of novel interventions will also need to consider the genotypes of participants, as the benefit may be determined by polymorphisms in an individual’s genetic background.

KEYWORDS:

• Atrophic age-related macular degeneration
• geographic atrophy
• complement
• inflammation
• visual cycle modulators
• antioxidants
• toxic by-products
• vascular enhancers
• stem cell therapy
• gene therapy

Article highlights

• We provide insights into understanding atrophic AMD pathogenesis;

• We outline the most recent atrophic AMD drug and molecular treatments that are currently being evaluated in clinical trials;

• We propose that extended release formulations will improve therapeutic outcomes; and

• We discuss the future of genetics-directed identification of new therapeutic targets for atrophic AMD.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

The authors were funded by an unrestricted grant from Research to Prevent Blindness, New York NY.