The TEASE-1 trial evaluated oral gildeuretinol acetate (ALK-001, a deuterated vitamin A) at 14 mg/day or 24 mg/day vs. placebo over 24 months in 50 randomized participants (aged 18–60) with ABCA4-related Stargardt disease (STGD1) who had well-demarcated retinal atrophy on fundus autofluorescence (FAF). An additional 54 natural history (NH) cases were included in the primary analysis.
Retinal atrophic lesion growth was 0.182 mm/yr with gildeuretinol vs. 0.232 mm/yr in the untreated group (placebo + NH), a mean difference of −0.050 mm/yr (95% CI, −0.072 to −0.027; P <.001), representing a 21.6% relative reduction. In the prespecified sensitivity analysis limited to randomized participants only, the reduction was 14.9% (−0.036 mm/yr; 95% CI, −0.062 to −0.009; P = .008). No treatment-related serious AEs, liver function abnormalities, night blindness, or dark adaptation difficulties were reported.
- The primary analysis pooled randomized participants with non-randomized natural history cases, which may introduce selection bias; the sensitivity analysis restricted to randomized participants showed a smaller, though still significant, effect. - Small sample size (n=50 randomized) limits precision and subgroup analyses. - Clinical relevance of the FAF lesion growth endpoint as a surrogate for vision loss remains uncertain.
Gildeuretinol acetate reduced the rate of retinal atrophic lesion growth by ~15–22% over 2 years in STGD1, with a favorable safety profile—no serious drug-related events or visual side effects were observed. Clinicians should await further trials confirming whether this imaging endpoint translates to preserved vision before adopting this agent.
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