Pilocarpine Hydrochloride Formulation Safe, Efficacious in Presbyopia Treatment

New findings showed the topical formulation of pilocarpine hydrochloride, 1.25% (AGN-190584) improved near vision and mesopic, high-contrast distance-corrected near visual acuity (DCNVA) in individuals with presbyopia.

Study data show the agent applied bilaterally once daily had statistically superior effects compared to vehicle in increasing the proportion of patients with improvement of 3 lines or more in mesopic DCNVA at hours 3 and 6 on day 30.

“Overall, AGN-190584 demonstrated an acceptable safety profile and did not impair distance vision; the overall benefit-risk supports the use of AGN-190584 for presbyopia management, and AGN-190584 recently became the first FDA-approved pharmacologic therapy for presbyopia,” wrote study author Michael R. Robinson, MD, Allergan, an AbbVie company.

The phase 3 GEMINI 1 study compared the efficacy and safety of AGN-190584 and vehicle in individuals with presbyopia. It enrolled patients with presbyopia, aged 40 - 55 years, at 36 sites in the US from December 2018 - October 2019, with analyses between February 2020 - December 2021.

The key inclusion criteria included:

• complaints of poor near vision impacting daily activities
• photopic, high-contrast corrected distance visual activity (CDVA) of 20/25 of better bilaterally
• mesopic, high-contrast distance-corrected near visual acuity (DCNVA, measured at 40 cm) of 20/40 to 20/100
• Photopic, near visual acuity correctable to 20.40 or better bilaterally
• Willingness to wear monofocal correction to achieve photopic, binocular CDVA of 20/32 or better

Individuals were randomized 1:1 to AGN-190584 or the AGN-190584 vehicle and the agent was administered bilaterally, once-daily for 30 days. The primary efficacy endpoint consisted of the proportion of patients gaining 3 or more lines in mesopic, high-contrast, binocular DCNVA on day 30, hour 3 with key secondary endpoints at hours 6 on day 30.

A total of 323 participants were randomized to AGN-190584 (n = 163) or vehicle (n = 160). Data show the mean age was 49.6 years and the baseline mean mesopic DCNVA was 29.2 letters.

Investigators observed the proportion of patients with an improvement of 3 or more lines of mesopic, high-contrast, binocular DCNVA was higher with AGN-190584 than vehicle on day 30 from hours 0.25 to 6 (P <.05).

On day 30, hour 3, data show the percentage of individuals with improvement of 3 or more lines in mesopic DCNVA was 30.7% (50 of 163) in the AGN-190584 group, compared to 8.1% in the vehicle group (difference, 22.5% [95% CI, 14.3% - 30.8%]; P <.001).

Then, at hour 6, 18.4% (30 of 163) and 8.8% (14 of 160) of participants had improvements of 3 or more lines with AGN-19058 and vehicle, respectively (difference, 9.7% [95% CI, 2.3% - 17.0%]; adjusted P = .01). The peak efficacy was observed at hour 1, when 41.6% (67 of 161) of participants treated with AGN-190584 had DCNVA improvement of 3 lines or more.

In a post-hoc analysis, no participants with DCNVA improvement of 3 lines or more had a loss of more than 5 letters in mesopic, high-contrast, binocular CDVA on day 30, hour 3.  A rapid onset of action (15 minutes) and duration of effect (≥6 hours) of AGN-190584 were maintained through day 30.

Overall, 35.0% (57 of 163) and 23.3% (37 of 159) of participants in the AGN-190584 and vehicle groups, respectively reported ≥1 treatment emergent adverse events, with mild headache being the most common.

The study, “Safety and Efficacy of AGN-190584 in Individuals With Presbyopia The GEMINI 1 Phase 3 Randomized Clinical Trial,” was published in JAMA Ophthalmology.