Opus Genetics reports positive phase 3 results for phentolamine ophthalmic solution 0.75%

Opus Genetics announced positive topline results from VEGA-3, its phase 3 trial evaluating phentolamine ophthalmic solution 0.75% for the treatment of presbyopia.

VEGA-3 is the second phase 3 clinical trial evaluating the safety and efficacy of Phentolamine Ophthalmic Solution 0.75% in patients with presbyopia. It is a multicenter, randomized, double-masked, placebo-controlled phase 3 study that enrolled 545 participants across 40 sites in the US. Patients were randomized in a 3:2 ratio to receive either phentolamine ophthalmic solution 0.75% or placebo, administered once daily in the evening.

According to the company,¹ the VEGA-3 trial (NCT06542497) met its primary endpoint of proportion of participants achieving a ≥15-letter Early Treatment Diabetic Retinopathy Study (ETDRS) (≥3-line) improvement in binocular DCNVA and with less than 5 letters of loss in binocular BCDVA from baseline at 12 hours post-dose on day 8, as compared to placebo. Results showed a statistically significant number of participants (27.2%) treated with phentolamine ophthalmic solution 0.75% met this endpoint, compared to 11.5% of patients on placebo (p<0.0001).

Additionally, 20.6% of patients in the phentolamine arm achieved ≥15-letter ETDRS (≥3-line) gain in DCNVA at 1-hour post-dose on day 1 compared to 6.1% of those receiving placebo (p=0.0002). No evidence of tachyphylaxis was observed after 6 weeks compared to the primary endpoint at day 8, 12 hours post-dose.

VEGA-3 patients will continue to be monitored for long-term safety over 48 weeks.

George Magrath, MD, CEO of Opus Genetics, commented on the results in a press release from the company,¹ saying, “The results of the VEGA-3 trial reinforce our belief that Phentolamine Ophthalmic Solution 0.75% could offer an option to improve near vision for millions of adults affected by presbyopia.”

The company noted that it plans to use data from both phase 3 VEGA-2 and VEGA-3 trials to support a “submission of an application” to the US Food and Drug Administration (FDA) in the second half of 2025.

Phentolamine Ophthalmic Solution 0.75% is a non-selective alpha-1 and alpha-2 adrenergic antagonist to reduce pupil size, administered as an eye drop. It is currently being evaluated in 2 phase 3 programs for the treatment of presbyopia and dim (mesopic) light vision disturbances after keratorefractive surgery (LYNX clinical program) and presbyopia (VEGA clinical program).

Recently, Opus released positive topline results from LYNX-2,² its phase 3 clinical trial evaluating phentolamine ophthalmic solution 0.75% for the treatment of chronic night driving impairment in keratorefractive patients with reduced mesopic vision.

References:

1. Opus Genetics announces VEGA-3 phase 3 trial met its primary endpoint for phentolamine ophthalmic solution 0.75% for the treatment of presbyopia. Published June 26, 2025. Accessed June 26, 2025. https://www.globenewswire.com/news-release/2025/06/26/3105692/0/en/Opus-Genetics-Announces-VEGA-3-Phase-3-Trial-Met-its-Primary-Endpoint-for-Phentolamine-Ophthalmic-Solution-0-75-for-the-Treatment-of-Presbyopia.html

2. Harp MD. Opus Genetics releases topline results from LYNX-2 evaluating phentolamine ophthalmic solution 0.75%. Published June 2, 2025. Accessed June 26, 2025. https://www.ophthalmologytimes.com/view/opus-genetics-releases-topline-results-from-lynx-2-evaluating-phentolamine-ophthalmic-solution-0-75-