Vega-1: A Phase 3, Double-Masked, Randomized, Placebo-Controlled Study Of Pos And Ldp In Presbyopic Patients

Purpose (250/750):

VEGA-1 aimed to evaluate the efficacy and safety of 0.75% Phentolamine Ophthalmic Solution (POS) alone and POS + LDP (low-dose pilocarpine) in presbyopic patients.

VEGA-1 (NCT04675151) was a randomized, placebo-controlled, double-masked Phase 3 trial evaluating the efficacy and safety of POS in combination with low-dose pilocarpine in presbyopic subjects conducted at 17 investigational sites in the United States.

The VEGA-1 multicenter, randomized, placebo-controlled, double-masked clinical trial enrolled subjects with distance-corrected near visual acuity (DCNVA) of 20/50 or worse. Participants were randomized to receive either POS or placebo (evening dosing), with or without a dose of LDP the morning after the 3rd or 4th dose of POS. Visual function testing was performed at 12, 13, and 18 hours after the last dose of POS. The primary efficacy endpoint was the percent of patients with improvement of ≥ 15 letters binocular photopic DCNVA relative to baseline, which was compared between treatment groups using logistic regression.

After 4 days of treatment, 30% of POS subjects demonstrated a ≥15 letters improvement in photopic binocular DCNVA compared to 12% in placebo at 12 hours post-treatment (p=0.0265); more POS vs. placebo subjects demonstrated ≥10 letters gain in DCNVA at 12 hours (50% vs. 28%; p=0.0046). Furthermore, a significant result was met with POS+LDP compared to placebo at 1-hour post-LDP dose on DCNVA primary endpoint (61% vs. 28%; p=0.003). POS+LDP showed statistical superiority to components at 30 minutes. POS+LDP had more responders than placebo at all time points from 30 minutes to 4 hours post-LDP dose. POS alone and POS+LDP were both well-tolerated with mild adverse events such as instillation site discomfort and conjunctival hyperemia.

The VEGA-1 trial demonstrated that two treatment options, POS alone and POS+LDP, resulted in a significant improvement in DCNVA compared to placebo. POS alone differentiates as a potential single daily presbyopia drop given its ≥12 hour durable efficacy. POS+LDP may allow further differentiation with added DCNVA improvement. Both treatments were well-tolerated with a favorable safety profile. These findings suggest that POS alone may be promising first-line monotherapy and, if needed, LDP adjunctive therapy to POS for patients with age-related blurry near vision. Further studies are planned to evaluate the safety and efficacy of POS and POS+LDP in presbyopic patients for registration.