Opus Genetics announced positive topline results from VEGA-3, its second pivotal phase 3 trial evaluating phentolamine ophthalmic solution 0.75% for the treatment of presbyopia. The VEGA-3 trial met its primary endpoint, with a statistically significant 27.2% of participants treated with the drug achieving a ≥ 15-letter improvement in binocular distance-corrected near visual acuity (DCNVA) and less than a 5-letter loss in binocular best-corrected distance visual acuity (BCDVA) at 12 hours post-dose on day 8, compared to 11.5% of patients on placebo (P < .001). The trial also met key secondary efficacy endpoints, reinforcing the benefit observed, the company said in a press release. 

According to the company, the primary endpoint was defined as the 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. In addition, 27.2% of participants treated with phentolamine ophthalmic solution 0.75% achieved a ≥ 15-letter improvement in DCNVA, with less than a 5-letter loss in BCDVA at 12 hours post-dose on day 8, compared to 11.5% of patients on placebo (P < 0.001), and 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).

The company also noted that significant patient-reported functional benefit at days 3 and 8 and week 6 were observed, with patients reporting satisfaction with near vision upon awakening (P < 0.001) and improvement in their near vision (P < 0.001). There was no evidence of tachyphylaxis observed after 6 weeks compared to the primary endpoint at day 8, 12 hours post-dose.

Phentolamine ophthalmic solution 0.75% demonstrated a safety profile consistent with previous trials, with no new safety signal identified and no treatment-related serious adverse events reported in this study. The most common (≥ 5%) treatment-emergent adverse events included conjunctival hyperemia, instillation site irritation, and dysgeusia, all predominantly mild. A low rate of headache (2.6%) was reported over the study period, the company said. 

VEGA-3 is the second phase 3 clinical trial evaluating the safety and efficacy of phentolamine ophthalmic solution 0.75% in subjects with presbyopia. VEGA-3 is a multicenter, randomized, double-masked, placebo-controlled phase 3 study that enrolled 545 participants across 40 sites in the United States. Subjects 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 Opus Genetics, VEGA-3 patients will continue to be monitored for long-term safety over 48 weeks. Additional information on the VEGA-3 study design is available on ClinicalTrials.gov (NCT06542497).

Opus Genetics and Viatris (through its affiliate) are parties to a global licensing agreement which provides for the development of phentolamine ophthalmic solution 0.75% and grants exclusive rights to Viatris to commercialize phentolamine ophthalmic solution 0.75% in the United States.