Objective:

To evaluate the efficacy of oral gildeuretinol acetate in slowing geographic atrophy progression in patients with age-related macular degeneration.

Approach:

• Study Design: Phase 2/3 SAGA randomized clinical trial involving 198 patients aged 60 years or older with geographic atrophy secondary to age-related macular degeneration.
• Intervention: Patients were assigned 2:1 to receive oral gildeuretinol acetate 14 mg once daily or placebo for 24 months.
• Primary Endpoint: Geographic atrophy lesion growth measured by fundus autofluorescence.
• Secondary Outcomes: Included low-luminance visual acuity (LLVA), best-corrected visual acuity (BCVA), VFQ-25, and FRI Index.

Key Findings:

• Geographic atrophy lesion growth was reduced by 13% with gildeuretinol compared to placebo, but this difference was not statistically significant.
• In a sensitivity analysis, lesion growth was reduced by 15% with gildeuretinol.
• Patients on gildeuretinol experienced less decline in LLVA and better vision-related quality of life.
• Safety findings were similar between treatment groups, with no new safety signals identified.

Interpretation:

The primary endpoint was not met, and secondary findings are considered exploratory.

Limitations:

• Enrollment was curtailed to 198 participants instead of the planned 300 due to the COVID-19 pandemic, which reduced statistical power.
• Approximately 70% of eyes contributed primary outcome data at 24 months.
• Favorable findings from sensitivity analysis and secondary endpoints are hypothesis-generating.

Conclusion:

Oral gildeuretinol acetate did not show statistically significant benefit for the primary endpoint, but exploratory effects support further evaluation in larger trials.

Sources:

• Ophthalmology Retina