May 14, 2020
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Study shows dose-dependent efficacy of emixustat in Stargardt disease

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The results of a phase 2 multicenter trial showed dose-dependent RPE65 inhibition efficacy of emixustat in patients with macular atrophy secondary to Stargardt disease. The 10 mg dose showed near-complete suppression of the rod b-wave recovery rate after photobleaching and was therefore selected for an ongoing phase 3 trial.

“Stargardt disease is the most common form of juvenile macular degeneration, characterized by deposition of toxic bisretinoids at the level of RPE. It is a rare disease for which no approved therapies are available,” Jeff Gregory, MD, said in a presentation at the virtual Association for Research in Vision and Ophthalmology meeting.

Emixustat is an orally administered once-daily small molecule that modulates the visual cycle, the chemical pathway thorough which vitamin A is recycled in the retina. By inhibiting RPE65, it reduces the availability of 11-cis-retinal, a precursor of toxic bisretinoids. In the study, which involved 23 subjects, the efficacy of emixustat at three different doses was evaluated by measuring the speed of recovery of rod b-wave after photobleaching on ERG, which depends on the availability of 11-cis-retinal and is therefore an indirect measure of RPE65 inhibition.

“Subjects treated with 10 mg showed near-complete suppression of the rod b-wave recovery rate post-photobleaching, with a median of 96.7%, whereas those treated with 5 mg showed moderate suppression with a median of 68%. No effect was observed for the 2.5 mg group, with a median of 12.2%,” Gregory said.

These results informed dose selection for an ongoing 24-month phase 3 trial of daily emixustat 10 mg vs. placebo for the treatment of macular atrophy secondary to Stargardt disease. The study will evaluate if emixustat reduces progression of macular atrophy on fundus autofluorescence. Secondary endpoints include changes in visual function parameters, other imaging parameters and quality of life. More than 189 subjects aged 16 years or older have been enrolled at 29 sites in 11 countries and randomly assigned 2:1 to receive emixustat 10 mg or placebo once a day for 24 months. Topline results are expected in the third quarter of 2022, Gregory said. – by Michela Cimberle

 

Reference:

Gregory J, et al. Randomized clinical trial evaluating the pharmacodynamics of emixustat in subjects with macular atrophy secondary to Stargardt disease. Presented at: Association for Research in Vision and Ophthalmology annual meeting; May 6, 2020 (virtual meeting).

Disclosure: Gregory reports he is an employee of Acucela and has a personal financial interest in the product mentioned.