Opus Genetics, Inc. announced two clinical program updates and a new regulatory designation status for its phentolamine ophthalmic solution (POS) 0.75%.
The formulation is currently under clinical investigation for the treatment of visual loss (decreased visual acuity [VA]) in low light conditions (DLD) associated with keratorefractive surgery.
Let’s start with this company.
The latest big news: Following its October 2024 purchase of Opus Genetics, Ocuphire Pharma, Inc. combined biotechnology and gene therapy into one merged company targeting inherited retinal diseases (IRDs). Read up on this.
- Included in the merger: Ocuphire’s POS (among other investigational candidates)
Talk about this formulation.
First thing to know: POS is already FDA-approved for the treatment of pharmacologically-induced mydriasis produced by adrenergic agonists or parasympatholytic agents under the name RYZUMVI.
- Currently: The formulation is under clinical investigation for presbyopia and reduced mesopic low contrast and night vision disturbances after keratorefractive surgery via a global license agreement with Viatris, Inc.
A few details about POS:
- It is an antimicrobial, preservative-free, topical eye drop formulation
- Phentolamine, its active ingredient, is key to its mechanism of action (MOA)
- About this: Phentolamine is a relatively non-selected alpha-1 and alpha-2 adrenergic agonist with antimicrobial properties
Explain this MOA.
To understand that, you’ll need to know how phentolamine works in the solution.
What it does: POS reversibly binds those aforementioned alpha-1 receptors (located on the iris dilator muscle) to reduce pupil diameter—all without impacting the ciliary muscle.
- How the pupil comes into play here: The radial iris dilator muscles around the pupil are primarily in charge of pupil dilation and become activated by the alpha-1 adrenergic receptors.
And what’s the clinical data on it thus far?
For presbyopia: Opus Genetics reported that a phase 2 and initial phase 3 trial on POS met their primary endpoints.
- The potential: For POS to provide a “non-invasive, convenient alternative to traditional corrective measures.”
For DLD following keratorefractive surgery: A phase 3 trial (LYNX-1) on POS met its primary endpoint, with 13% of subjects gaining 15 or more Early Treatment Diabetic Retinopathy Score (ETDRS) letters of mesopic low contrast distance VA at Day 8 vs 3% on placebo (p<0.05).
- The potential: To become the first FDA-approved therapy for visual disturbances under low light conditions.
Got it. Now let’s get into this regulatory update.
Opus Genetics reported that the FDA granted Fast Track designation (FTD) to POS as a treatment for:
- Significant chronic night driving impairment with concomitant increased risk of motor vehicle accidents and debilitating loss of best spectacle-corrected mesopic vision in keratorefractive patients with photic phenomena (such as glare, halos, or starbursts)
See here for details on the significance of this designation (which, essentially, expedites the review of new drugs for serious medical conditions)—including the company’s possible eligibility for Priority Review.
Next up: this enrollment news.
Both updates pertain to phase 3 trials involving POS.
First: VEGA-3 (NCT06542497)
- The design: Randomized, double-masked, placebo-controlled, multicenter trial
- The participants: 545 (aged 45 to 64) diagnosed with presbyopia
- The setup: Randomized 3:2 to receive one dose of either of the following each night:
- POS 0.75%
- Placebo solution
- The duration: Eight days (with patients followed up to 48 weeks)
- The primary outcome measure: Percentage of participants with ≥ 15 letters of improvement in binocular DCNVA and with < 5 ETDRS letters of loss in binocular distance-corrected VA (BCDVA) from baseline, and comparing POS 0.75%-treated participants to placebo-treated participants at 12 hours post-dose at Visit 4.
- Measured at Day 8
And the other phase 3 study?
The second: LYNX-2 (NCT06349759)
- The design: Randomized, double-masked, placebo-controlled, multicenter trial
- 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.
Take note: This study is operating under a Special Protocol Assessment (SPA) from the FDA, in which the agency agreed that its protocol and planned statistical analysis “would adequately address objectives supporting regulatory submission and a potential future marketing application in this indication.”
And what are the enrollment updates with these trials?
In regards to the VEGA-3 study: Opus Genetics reported that participant enrollment has officially concluded.
As for the LYNX-2 study: After enrolling the first participants in April 2024, the trial is said to be “more than 95% enrolled” with completion expected before the end of the first half (H1) of 2025.
When should we expect data readouts?
The VEGA-3 study is expected to conclude in October 2025 (primary completion; the date when the last data point for the primary outcome measure is collected from the final participant) and June 2026 (complete study completion, when all data points are collected from participants).
Meanwhile, the LYNX-2 study’s completion dates are toward the end (September for primary and December for complete) of this year.