Lynx-1: Phentolamine Ophthalmic Solution For Dim Light Vision Disturbance

The LYNX-1 study evaluated the efficacy and safety of 0.75% phentolamine ophthalmic solution (POS) in the treatment of dim light vision disturbance (DLD) in adult subjects. This Phase 3, randomized, double-masked, placebo-controlled study enrolled 145 adult subjects, including 25 post-LASIK patients

LYNX-1 (NCT04638660) was a randomized, placebo-controlled, double-masked Phase 3 trial evaluating the efficacy and safety of POS in treating DLD conducted at 17 investigational sites in the United States

Subjects were randomized 1:1 to receive POS or placebo in both eyes daily at bedtime. Visual function testing and ophthalmologic examination were performed on study Day 8 and Day 15. The primary efficacy endpoint was the percent of POS-treated subjects with ≥3 lines of improvement in mesopic low-contrast distance visual acuity (mLCVA) relative to placebo. Secondary efficacy endpoints and safety measures were assessed at Day 8 and 15. 

The primary efficacy endpoint was met at Day 8 with 13% of POS subjects gaining ≥ 3 lines of mLCVA versus 3% on placebo (p<0.05). The effect of POS increased at Day 15, with 21% of subjects gaining ≥3 lines of mLCVA compared to 3% on placebo (p<0.01). POS also significantly increased the percent of subjects gaining ≥ 2 lines at Day 8, with 41% versus 22% on placebo (p<0.05), and at Day 15, with 44% versus 23% on placebo (p<0.05). At Day 8, 4 LASIK subjects treated with POS gained ≥3-line mLCVA compared to 1 responder in the placebo arm. POS showed a favorable safety and tolerability profile. There were no serious adverse events or withdrawals due to AEs. AEs were primarily mild with low incidence. 

This is the first pivotal Phase 3 clinical trial demonstrating that a modest reduction in pupil diameter from POS treatment can improve visual function in patients with DLD, including those with history of LASIK surgery. In addition, there was no evidence of tachyphylaxis, retinal tears or detachment, consistent with POS not engaging the ciliary muscle. Based on the favorable safety and positive efficacy results of LYNX-1, POS has the potential to be the first treatment option to improve night vision disturbances, diminish unwanted photic phenomenon, and improve quality of life and quality of vision in patients with DLD.