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 Phentolamine Ophthalmic Solution 0.75% achieving a ≥15-letter improvement in binocular distance-corrected near visual acuity (DCNVA), with 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<0.0001). 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<0.0001), 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<0.0001) and improvement in their near vision (p<0.0001). 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 and all of which were 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.