Allergan, an AbbVie company, announced the Phase 3 GEMINI 1 and 2 clinical trials evaluating the efficacy, safety and tolerability of investigational AGN-190584 (pilocarpine 1.25%) ophthalmic solution for the treatment of symptoms associated with presbyopia, met their primary efficacy endpoint. Additional details of these studies will be presented at future medical meetings and will serve as the basis for the New Drug Application submission to U.S. Food and Drug Administration (FDA) in the first half of 2021.

In GEMINI 1, the primary endpoint was met with a statistically significant greater proportion of participants treated with AGN-190584 who gained three lines (the ability to read three additional lines on a reading chart) or more in mesopic (in low light), high contrast, binocular Distance Corrected Near Visual Acuity (DCNVA) at Day 30, Hour 3 versus the vehicle (placebo). In GEMINI 2, the primary endpoint was also met with a statistically significant greater proportion of participants treated with AGN-190584 who gained three lines or more in mesopic, high contrast, binocular DCNVA without loss of greater than five letters in Corrected Distance Visual Acuity (CDVA) with the same refraction at Day 30, Hour 3 versus the vehicle. Further details including additional efficacy and safety results are included in the "About the Studies" section below.

Roughly 128 million people in the U.S. experience presbyopia, a common and progressive eye condition that reduces the eye's ability to focus on near objects and usually impacts people after age 40. Results from a survey of 1,339 respondents, age 40-55, found that 90% were frustrated or irritated with presbyopia.

"Presbyopia symptoms can significantly disrupt everyday activities like reading, using a smartphone, working, and cooking," said George O. Waring IV, M.D., FACS, medical director, Waring Vision Institute, South Carolina. "While individuals currently have several options to help manage presbyopia, including glasses, contact lenses and surgery, research has shown that the majority of presbyopic individuals are frustrated with the use of contact lenses or glasses. These GEMINI findings support the possibility of another treatment option for people living with presbyopia."

In a non-presbyopic eye, the clear lens behind the iris can change shape and focus light to the retina, making it easier to see things up close. In a presbyopic eye, the clear lens hardens and does not change shape as easily, making it difficult to focus on near objects. AGN-190584 is an investigational eye drop designed to treat symptoms of presbyopia and is instilled in both eyes.

"Our research shows that the symptoms associated with presbyopia can significantly impact people's daily lives," said Michael R. Robinson, M.D., vice president, global therapeutic area head, ophthalmology, AbbVie. "The positive results from the GEMINI studies show the potential of this investigational optimized formulation of pilocarpine 1.25% to treat symptoms associated with presbyopia."

GEMINI 1 and 2 enrolled a total of 750 patients randomized in a one-to-one ratio of vehicle (placebo) to AGN-190584 (pilocarpine 1.25%). AGN-190584 was administered bilaterally, once-daily, for 30 days in both GEMINI 1 and 2 participants with presbyopia. In the GEMINI studies, AGN-190584 demonstrated significant near vision gains in mesopic (in low light) conditions without a loss of distance vision. There were no treatment emergent serious adverse events observed in any AGN-190584 treated participants. The most common treatment emergent non-serious adverse events occurring at a frequency of ≥3% in AGN-190584 treated participants were headache, conjunctival hyperaemia, vision blurred, and eye pain. In both studies, the primary endpoint was met. The majority of secondary endpoints were also met in both studies, including a significant improvement in patient-reported outcomes (PROs) such as an increase in vision-related reading ability, and reductions in the impact of presbyopia on daily life and use of coping behaviors to manage presbyopia.

AGN-190584 is an investigational optimized formulation of pilocarpine, a cholinergic muscarinic receptor agonist, that is being investigated for treating symptoms associated with presbyopia as a topical, once-daily drop delivered by a proprietary vehicle.

The proposed mechanism of action of AGN-190584 is through dynamic pupil modulation, an effect in which the iris sphincter is contracted to achieve pupil size reduction in an optimal range. The goal of this pupil size reduction is to increase depth of focus. Secondarily, it is believed to allow for increased accommodation through mild contraction of the ciliary muscle.