A Phase 2a clinical trial of ALK-001 in geographic atrophy

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 DESCRIPTION (provided by applicant): The long-term goal of this work is to develop an oral drug for the prevention of age-related macular degeneration (AMD). AMD is the leading cause of blindness in the United States, with 8 million Americans diagnosed or at risk of irreversibly losing vision, and over 2 million people who already have debilitating vision loss. Currently, there is no FDA-approved preventative treatment for AMD. One of the earliest changes in the retina that precede symptoms of AMD is the formation of toxic vitamin A dimers. ALK-001 is a chemically-modified vitamin A, in which 3 hydrogen atoms have been replaced by 3 deuterium atoms at carbon number 20. Replacing the retina's vitamin A with ALK-001 slows the formation of toxic vitamin A dimers. To date, ALK-001 is the only small molecule designed to prevent the dimerization of vitamin A that has demonstrated functional preservation of visual function in animal models. The central hypothesis of this work is that retarding vitamin A dimerization will slow the development and/or progression of AMD. The specific objective of this application is to further develop ALK-001 and generate clinical data so that phase 3 or 4 confirmatory clinical trials can be designed to assess the extent to which inhibiting the dimerization of vitamin A slows the development and/or progression of AMD. We plan to achieve this goal by completing the following specific aims: AIM 1: Determine the feasibility of manufacturing ALK-001 on a commercial scale. This will be achieved by assessing the limitations of our current synthetic route to determine if it can be used to manufacture ALK- 001 on a commercial scale. AIM 2: Evaluate the effect size of ALK-001 on the progression of geographic atrophy (GA) due to AMD. This will be achieved by performing an 18-month double-masked, placebo-controlled study in 80 subjects with geographic atrophy. An oral drug to prevent the development and/or worsening of AMD would have a tremendous impact on the quality of life of millions of Americans. The dimerization of vitamin A has long been hypothesized to be a major contributor of the development of AMD. However, we lack clinically-amiable strategies to safely prevent its dimerization. This limits our ability to determine the extent to which dimerization participates in the progression of AMD. ALK-001 is a new compound that has been shown to prevent the dimerization of vitamin A without negatively affecting the visual cycle or depriving the photoreceptors of vitamin A, and thus could possibly slow the progression of AMD.