Safety and Efficacy of AGN-190584 in Individuals With Presbyopia: The GEMINI 1 Phase 3 Randomized Clinical Trial

Abstract

Importance: AGN-190584 (Allergan, an AbbVie company) is an optimized topical formulation of pilocarpine hydrochloride, 1.25%, designed for managing presbyopia and enhanced with a proprietary vehicle.

Objective: To evaluate the efficacy and safety of pilocarpine hydrochloride, 1.25%, in individuals with presbyopia.

Design, setting, and participants: This vehicle-controlled, participant- and investigator-masked, randomized, phase 3 clinical study, GEMINI 1, enrolled individuals with presbyopia, aged 40 to 55 years, at 36 sites in the United States from December 21, 2018, to October 31, 2019. Analysis took place between February 2020 and December 2021.

Interventions: AGN-190584 or the AGN-190584 formulation vehicle was administered bilaterally, once daily for 30 days.

Main outcomes and measures: The proportion of participants with improvement of 3 or more lines in mesopic, high-contrast, binocular distance-corrected near visual acuity (DCNVA) at hours 3 and 6 on day 30 were the primary and key secondary efficacy end points, respectively. Safety measures included adverse events.

Results: Of 323 participants who were randomized, 235 (72.8%) were female and 292 (90.4%) were White. The mean (SD) age was 49.6 (3.5) years, and the baseline mean (SD) mesopic DCNVA was 29.2 (6.3) letters. A total of 163 individuals were randomized to AGN-190584 and 160 were randomized to vehicle. GEMINI 1 met its primary and key secondary efficacy end points. On day 30, hour 3, the percentage of participants with improvement of 3 or more lines in mesopic DCNVA was 30.7% (50 of 163) in the AGN-190584 group and 8.1% (13 of 160) in the vehicle group (difference, 22.5% [95% CI, 14.3%-30.8%]; adjusted P < .001). At hour 6, those percentages were 18.4% (30 of 163) and 8.8% (14 of 160), respectively (difference, 9.7% [95% CI, 2.3%-17.0%]; adjusted P = .01). At hour 8, the between-group difference in 3 or more lines of mesopic DCNVA gains was not statistically significant, but clinically relevant prespecified outcome measures demonstrated AGN-190584 superiority to vehicle in least-squares mean (SE) mesopic DCNVA change from baseline at hour 8 (5.4 [0.51] vs 3.6 [0.52] letters; P = .009) and photopic distance-corrected intermediate visual acuity at hour 8 (3.9 [0.44] vs 2.4 [0.45] letters; P = .01) and hour 10 (3.5 [0.46] vs 1.7 [0.47] letters; P = .004). No participants with mesopic DCNVA improvement of 3 or more lines at hour 3 had losses of more than 5 letters in mesopic, high-contrast, binocular-corrected distance visual acuity. The onset of effect was at 15 minutes. AGN-190584 demonstrated an acceptable safety and tolerability profile.

Conclusions and relevance: AGN-190584 demonstrated superiority over vehicle in mesopic DCNVA on day 30, hours 3 and 6, with an acceptable safety profile. AGN-190584 is a safe and efficacious topical therapy for presbyopia through 30 days.

Trial registration: ClinicalTrials.gov Identifier: NCT03804268.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Waring reported personal fees from Allergan (an AbbVie company) during the conduct of the study and outside the submitted work. Dr Price reported grants from AbbVie, Alcon, Aerie Pharmaceuticals, Kala Pharmaceuticals, Allergan (an AbbVie company), and EyePoint; ownership interests in Staar Surgical, RxSight, and Strathspey Crown; and personal fees from Haag-Streit and Gebauer outside the submitted work. Dr Wirta has consulted for Allergan (an AbbVie company) and Eyenovia and has received grant support from Aerpio, Allergan (an AbbVie company), Annexon, Dompe, Eyenovia, Mallinckrodt, Nicox, Novaliq, Novartis, SilkTech, and Santen. Dr McCabe reported personal fees from Allergan (an AbbVie company) during the conduct of the study; personal fees from Bausch and Lomb, Alcon, Visus, Surface Pharma, Johnson and Johnson Vision, and Zeiss outside the submitted work. Drs Gore and Robinson reported a patent to 10,610,518 on presbyopia treatments issued. Ms Safyan and Drs Guo, Gore, Liu, and Robinson are full-time employees of AbbVie Inc and may hold AbbVie stock. No other disclosures were reported.

Figures

Figure 1.. Participant Disposition

The adverse events leading to study discontinuation were bradycardia (n = 1) and dyschromatopsia and bilateral visual field defect (n = 1) in the AGN-190584 group and corneal abrasion (n = 1) and headache and migraine (n = 1) in the vehicle group. aParticipants could fail screening owing to multiple reasons.

Figure 2.. High-Contrast, Binocular Visual Outcomes at Day 30

Mesopic and photopic conditions were defined as lighting 10 to 11 lux and 251 lux or more, respectively, measured at the target. DCIVA indicates distance-corrected intermediate visual acuity; DCNVA, distance-corrected near visual acuity. aP < .05.