Ocuphire Pharma has commenced its Phase 3 VEGA-3 clinical trial, evaluating phentolamine ophthalmic solution 0.75% as a potential treatment for presbyopia. The first participant has been dosed in this randomized, double-masked, placebo-controlled, multi-center study.
The VEGA-3 trial (NCT06542497) aims to assess the efficacy and safety of phentolamine ophthalmic solution 0.75% in 545 participants diagnosed with presbyopia. Participants will be randomized in a 3:2 ratio to receive either phentolamine ophthalmic solution 0.75% or a placebo, administered as one drop each evening. The primary endpoint is the percentage of participants achieving a 15-letter improvement in photopic binocular distance-corrected near visual acuity (DCNVA) on day 8 following the initial visit. The improvement in binocular DCNVA will be measured against each participant's baseline value, with a total follow-up period of 48 weeks for chronic safety data collection. Recruitment is planned across up to 40 sites in the U.S.
Addressing Presbyopia with Novel Approach
Presbyopia, a common age-related condition affecting an estimated 128 million Americans and over 2 billion people worldwide, involves the gradual loss of the ability to focus on near objects. This often necessitates the use of reading glasses or bifocals. Phentolamine ophthalmic solution 0.75% is under development as a non-invasive and convenient alternative to these traditional corrective methods.
George Magrath, MD, MBA, MS, CEO of Ocuphire, stated, "Our goal is to provide a safe, long-lasting, effective solution that restores near vision and enhances overall visual performance in people with presbyopia, under both daytime and nighttime conditions. We are pleased to begin the VEGA-3 trial, building on the positive results generated in our prior presbyopia studies, which have shown a rapid onset of action, favorable safety profile, and sustained duration of effect that are promising at this stage."
Mechanism of Action and Prior Studies
Phentolamine ophthalmic solution 0.75% functions as a non-selective alpha-1 and alpha-2 adrenergic antagonist, designed to reduce pupil size by blocking alpha-1 receptors on the radial iris dilator muscles. In addition to presbyopia, it is also being investigated for dim (mesopic) light vision disturbances following keratorefractive surgery.
Magrath referenced previous studies, including the VEGA-2 trial (NCT05646719), which also assessed phentolamine ophthalmic solution 0.75% for presbyopia. The VEGA-2 study was a randomized, double-masked, placebo-controlled, multi-center Phase 3 trial that evaluated the efficacy of phentolamine ophthalmic solution 0.75% alone and with adjunctive low dose pilocarpine to improve DCNVA. The study enrolled 333 participants aged 40 to 64 years and achieved its primary endpoint.
Anticipated Timeline and Regulatory Pathway
Ocuphire anticipates that data from the VEGA-3 trial will support a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA). Top-line data from the VEGA-3 Phase 3 trial are expected in the first half of 2025.
Further Development Programs
Ocuphire is also advancing the LYNX-2 Phase 3 trial, evaluating phentolamine ophthalmic solution 0.75% for decreased visual acuity under low light conditions following keratorefractive surgery, with top-line data expected in the first quarter of 2025. The LYNX-2 trial is being conducted under a Special Protocol Assessment (SPA) with the FDA.
