Safety and Efficacy of AGN-241622 for Presbyopia: Results From a First-in-Human, Phase 1/2, Randomized, Vehicle-Controlled Study.

PURPOSE: Evaluate safety and efficacy of AGN-241622 ophthalmic solution in healthy individuals and individuals with presbyopia.

METHODS

This vehicle-controlled, participant- and investigator-masked, randomized phase 1/2 study enrolled healthy individuals and individuals with presbyopia, aged 40-65 years, at 10 sites in the US from 30 July 2020 to 05 Dec 2022 (NCT04403763). Stage 1 cohorts were randomized (3:1) sequentially to receive AGN-241622 (0.01%, 0.03%, or 0.1% ophthalmical solution) or vehicle once in the left eye. Stage 2a cohorts were randomized (3:1) sequentially to receive AGN-241622 (0.01%, 0.03%, or 0.1%) or vehicle daily in both eyes for 14 days. Safety included treatment-emergent adverse events (TEAEs). Efficacy included change in pupil diameter and high-contrast, binocular distance-corrected near visual acuity.

RESULTS

A total of 80 participants were randomized to AGN-241622 (n = 61) or vehicle (n = 19), and 76 completed the study; baseline characteristics were well balanced. All TEAEs were of mild severity. All but 1 TEAE (not related to AGN-241622) resolved. In Stage 1, the most frequently reported ocular TEAE was increased lacrimation (AGN-241622 0.01% [n = 4], AGN-241622 0.03% [n = 1], and vehicle [n = 1]). In Stage 2a, there were 2 TEAEs of mild severity (dermatitis) in 1 participant who received AGN-241622 0.1% that led to discontinuation, which resolved and was unrelated to AGN-241622. Modest efficacy in pupil reduction and vision improvement was also observed.

CONCLUSIONS

AGN-241622 ophthalmic solution was well tolerated, and modest efficacy was observed in binocular distance-corrected near visual acuity in presbyopic participants with the drug concentrations assessed in this study.