The first patient dosing is underway for Opus Genetics, Inc.’s third phase 3 clinical trial evaluating phentolamine ophthalmic solution (POS) 0.75% for the treatment of significant, chronic night driving impairment in keratorefractive patients with reduced mesopic vision.
Let’s start with this ophthalmic solution.
As we’ve already routinely covered POS 0.75% this past year, here’s a brief rundown:
What it is: An antimicrobial, preservative-free (PF), topical solution formulated with the active ingredient: phentolamine (see here for details on this).
- Check out its mechanism of action, which involves pupil dilation.
And its current indications?
We’ll start with its FDA-approved indication—under the name RYZUMVI—for the treatment of pharmacologically-induced mydriasis produced by adrenergic agonists or parasympatholytic agents.
Other investigational indications (via a globe license agreement with Viatris, Inc.) include:
- Presbyopia
- Reduced mesopic low contrast and night vision disturbances (NVDs) after keratorefractive surgery (our topic of discussion)
- Granted FDA Fast Track designation
Looking specifically at that last indication … how does POS 0.75% treat this?
Per Opus Genetics: The eye drop is designed to “moderately reduce pupil size in low-light conditions to potentially decrease the impact of aberrant peripheral light rays entering the pupil while maintaining retinal contrast sensitivity.”
The potential: To become the first FDA-approved therapeutic for patients experiencing NVDs.
Now talk about this phase 3 trial.
The LYNX-3 trial (NCT07140783) is a multicenter, randomized, double-masked, placebo-controlled study being conducted under a Special Protocol Assessment (SPA) with the following setup:
- The participants: An estimated 200 patients (aged ≥18) with decreased visual acuity (VA) in mesopic conditions following keratorefractive surgery, including:
- Laser-assisted in situ keratomileusis (LASIK)
- Photorefractive keratectomy (PRK)
- Small-incision lenticule extraction (SMILE)
- Radial keratotomy (RK)
- The plan: Patients to be randomized 1:1 to receive once-daily evening doses of POS 0.75% or placebo for an estimated 2 weeks
And what’s being measured?
The primary endpoint is the percentage of participants achieving a ≥15-letter Early Treatment Diabetic Retinopathy Study (ETDRS) (≥3-line) improvement from baseline in mesopic low-contrast visual acuity (mLCVA) in the study eye at Day 15.
Secondary endpoints include:
- Patient-reported outcomes related to night driving, glare, halos, and starbursts
- Binocular visual function measures
- Safety assessments (ocular and systemic evaluations)
So when might data be available?
Good question. The study is expected to conclude in March 2026—though interim data may be released earlier.
Gotcha. In the meantime, any clinical evidence available yet for POS 0.75%?
There is, as the LYNX-3 is actually the third phase 3 trial for this indication. The first was LYNX-1 (check out its favorable safety and efficacy data) and the second was LYNX-2 (NCT06349759).
In fact, we just reported on positive topline data from LYNX-2 this past June.
- The highlights version of those findings: The study met its primary endpoint (at Day 15) and patient-reported outcomes indicated "improvements in night-driving vision, enabling patients to function more effectively in low-light, low-contrast conditions.”
See here for info on adverse events and POS 0.75%’s safety profile.
Sounds like promising data thus far.
Indeed. And that’s not including recent clinical findings from the ongoing phase 3 VEGA-3 trial for POS 0.75%’s presbyopia indication (which we covered in July 2025).
And what’s the plan for a potential second regulatory submission?
That’s to be determined. Although, as we reported in July, Opus Genetics did note an intent to use its phase 3 presbyopia data to support a new drug application (NDA) submission sometime in the second half (H2) of 2025.
So stay tuned for updates on that …