Opus Genetic, Inc. announced the phase 3 LYNX-2 study has met its primary endpoint in evaluating phentolamine ophthalmic solution (POS) 0.75% for the treatment of significant, chronic night driving impairment in keratorefractive patients with reduced mesopic vision.
Nice! First, a refresher on POS 0.75%.
To start, this is an antimicrobial, preservative-free, topical eye drop formulation.
About its active ingredient: Phentolamine is a reversible, nonselective alpha-1 and alpha-2 adrenergic agonist with antimicrobial properties.
And its MOA?
POS’s mechanism of action (MOA) involves reversibly binding those aforementioned alpha-1 receptors—positioned on the iris dilator muscle—to reduce pupil diameter.
- Importantly: This is done without impact on the ciliary muscle.
The pupil effect: The radial iris dilator muscles around the pupil are primarily in charge of pupil dilation and become activated by the alpha-1 adrenergic receptors.
Gotcha. Now, this is already FDA-approved, right?
Indeed it is; however, its approved indication is for the treatment of pharmacologically-induced mydriasis produced by adrenergic agonists or parasympatholytic agents.
The brand name: RYZUMVI.
- Check out more about this approval here.
Plus: The therapeutic was also granted Fast Track designation earlier this year.
And what other target indications is it under development for?
Presbyopia.
In fact: Opus Genetics, POS met the primary endpoints in a phase 2 and phase 3 trial evaluating its ability to treat presbyopia.
Alrighty … to set the stage, let’s talk prior clinical data.
Per Opus Genetics, POS met the primary endpoints in a phase 2 and a phase 3 trial evaluating its ability to treat presbyopia.
But in regards to POS’s proposed indication for keratorefractive patients with visual disturbances under mesopic, low-contrast conditions (as part of a global license agreement with Viatris, Inc.):
- The gene therapy was evaluated in the first phase 3 LYNX-1 trial
And its performance in that study?
POS also met the trial’s primary endpoint, with 13% of participants gaining 15+ Early Treatment Diabetic Retinopathy Score (ETDRS) letters of mesopic low contrast distance visual acuity (VA) at Day 8.
- This compared to placebo-treated patients, in which just 3% achieved the same gain in ETDRS letters.
What was the significance of those findings?
This was the first pivotal phase 3 trial that demonstrated a modest reduction in pupil diameters from POS treatment could improve visual function in this patient base.
- Plus: There was no evidence of tachyphylaxis or retinal detachment.
The big picture: LYNX-1’s favorable safety and positive efficacy data indicated that POS could become the first treatment option for:
- Improving night vision disturbances (NVD)
- Eliminating unwanted photic phenomena
- Improving quality of life and vision in this patient base
Now to this LYNX-2 study.
The trial was conducted under a Special Protocol Assessment (SPA) from the FDA, where its protocol and planned statistical analysis will be used to support a future regulatory submission and potential marketing application for the proposed indication.
As for the study details, LYNX-2 is designed as a randomized, double-masked, placebo-controlled, multicenter trial (NCT06349759).
- The participants: 200 (estimated; aged 18+) who underwent keratorefractive surgery and then reported decreased VA under low light conditions
- The setup: Randomized to receive a daily dosing of one of the following:
- POS 0.75%
- Placebo solution
- The duration: 15 days
- The primary outcome measure: Participants with an increase of at least 15 ETDRS letters read (≥ 3 lines) in the study eye in mesopic distance low contrast VA (mLCVA) compared to baseline (Day 1 pre-dose) at Day 15.
And these topline results?
Most importantly: The study met its primary endpoint, gaining ≥15 letters (≥3-line) in mesopic low contrast distance visual acuity in comparison to placebo, with:
- 17% of POS-treated patients achieving this (p<0.05)
- 9.2% of placebo-treated patients achieving this (p<0.05)
How did these patients’ nighttime driving impairment fare?
Patient-reported outcomes indicated "improvements in night-driving vision, enabling patients to function more effectively in low-light, low-contrast conditions,” according to George Magrath, MD, Opus Genetics CEO.
- Outcomes were reported using the validated Vision and Night Driving Questionnaire (VND-Q).
These “functional improvements” extended to patients who were previously unable to see the road due to oncoming headlights, as well as difficulty seeing due to glare when driving at either dawn or dusk.
- The data builds on the earlier results reported in the LYNX-1 trial, Dr. Magrath noted.
Nice! Any adverse events?
POS demonstrated a favorable safety profile similar to that seen in prior clinical trials—and with no new safety signals, Opus Genetics reported.
In line with this: There was also “no evidence of tachyphlaxis out to Week 6 of dosing.”
So what’s next?
Study participants will continue to be monitored for long-term safety over a 48-week period.
And on the subject of another ongoing trial evaluating POS (for presbyopia, this time): The phase 3 VEGA-3 study (NCT06542497) is expected to conclude in June 2026, with interim data likely to be released before then.