Gildeuretinol acetate looks good for Stargardt disease

Treatment with gildeuretinol acetate capsules helps slow the growth of retinal atrophic lesions in individuals with Stargardt disease, according to the phase II TEASE-1 trial.

TEASE-1 included patients ages 12 years and above who had a clinically diagnosed Stargardt disease with well-demarcated area(s) of significantly reduced autofluorescence, supported with at least one ABCA4 disease-causing or likely disease-causing variant.

A total of 50 patients (mean age 44.3 years, 56 percent female) were randomly assigned to receive gildeuretinol acetate at 14 or 24 mg (n=30) or placebo (n=10) for 24 months or placebo for 12 months followed by gildeuretinol for 12 months (crossover group, n=10). A natural history group including 54 patients were included.

The primary endpoint was the growth rate of well-delineated and homogeneous areas of retinal atrophic lesions over 24 months of treatment, as measured using fundus autofluorescence imaging. Treatment-emergent adverse events (AEs), serious AEs, and clinical laboratory assessments were also performed.

The growth rate of retinal atrophic lesions was 0.182 mm/year with gildeuretinol acetate vs 0.232 mm/year in the combined placebo and natural history groups, corresponding to a mean difference of −0.050 mm/year (95 percent confidence interval [CI], −0.072 to −0.027; p<0.001) or a relative reduction of 21.6 percent.

The result was replicated in a sensitivity analysis restricted to randomized participants. The growth rate of retinal atrophic lesions was significantly reduced with gildeuretinol acetate vs placebo (0.206 vs 0.242 mm/year; mean difference, −0.036 mm/year, 95 percent CI, −0.062 to −0.009; p=0.008), with a 14.9-percent relative reduction.

In terms of safety, the majority of AEs were mild or moderate and equally distributed between groups. None of the patients had treatment-related serious AEs, clinically significant liver function abnormalities, or self-reported night blindness or dark adaption difficulties.