Ocuphire Pharma, Inc. announced the first patient enrolled in its phase 3 study evaluating the use of phentolamine ophthalmic solution 0.75% (PS) for decreased visual acuity (VA) under low (mesopic) light conditions after keratorefractive surgery.
Refresh me on the company.
Founded in 2018 and headquartered in Farmington Hills, Michigan, Ocuphire Pharma is a late clinical-stage ophthalmic biopharmaceutical company developing and commercializing therapies to treat retinal and refractive eye disorders.
Most notably: The company was granted FDA approval in September 2023 for RYZUMVI (phentolamine ophthalmic solution) 0.75%, indicated for the treatment of pharmacologically-induced mydriasis produced by adrenergic agonists or parasympatholytic agents.
Now talk about this solution.
Developed in partnership with Viatris, Inc., which is funding its development, phentolamine ophthalmic solution 0.75% is a preservative-free, topical eye drop formulation.
As the formulation's active ingredient, phentolamine is a relatively non-selected alpha-1 and alpha-2 adrenergic agonist.
More about this: Phentolamine can also enhance antimicrobial properties of macrolide antibiotics against Gram-negative bacteria.
And its mechanism of action?
The phentolamine solution works to reversibly bind the alpha-1 adrenergic receptors located on the iris dilator muscle, resulting in a potential reduction in pupil diameter.
Take note: Pupil dilation is largely controlled by the radial iris dilator muscles around the pupil—which can be activated by the alpha-1 adrenergic receptors.
What other indications may PS be used for?
FDA-approved indication:
- Reversal of mydriasis (RM) under the RYZUMVI brand name
- Commercially launched in the U.S. earlier this month
Under investigation:
- Night vision disturbances (NVD)
- Presbyopia (used with low-dose 0.4% pilocarpine eye drops)
- VEGA-2 phase 3 clinical trial is ongoing
Gotcha. So about this phase 3 study…
The LYNX-2 trial was initiated based on a Special Protocol Assessment (SPA) granted by the FDA in January 2024 (see here for details on what an SPA entails).
The study is being conducted as a multi-center, randomized, double-masked, placebo-controlled registration trial (NCT06349759) evaluating the use of PS in an estimated 200 participants within the United States.
Patient criteria?
Among the study’s inclusion criteria, participants must be at least aged 18+ and with a history of refractive surgery, including:
- Photorefractive keratectomy (PRK)
- Laser-assisted in situ keratomileusis (LASIK)
- Small-incision lenticule extraction (SMILE)
- Radial keratotomy (RK)Click here for the complete list of inclusion and exclusion criteria.
And the setup?
Participants are being randomized to receive one of the following dosages over a 15-day period:
- Once daily dosing of PS
- Once daily dosing of vehicle
What’s being measured?
Primary endpoint includes the number of participants with an increase of at least 15 Early Treatment Diabetic Retinopathy Score (ETDRS) read (≥ 3 lines) in the study eye in mesopic distance low contrast visual acuity (mLCVA) compared to baseline (Day 1 pre-dose) at Day 15.
Alrighty… so is there any previous data on PS?
There is! The first phase 3 trial (LYNX-1) was a placebo-controlled, double-masked, multiple-dose phase 3 study (NCT04638660) evaluated the use of the phentolamine solution (vs a placebo) in subjects with dim light vision disturbances when administered once daily at/near bedtime for 14 days.
Learn more about that study here.
Give me those details.
The LYNX-1 study met its primary endpoint, with a “statistically significant greater percentage of (PS)-treated subjects having gained 15 or more letters of (mLCVA) at Day 8, compared to placebo (13% vs 3%; p<0.05).”
PS also demonstrated a favorable safety and tolerability profile with no serious adverse events (AEs).
See here for more findings.
What’s the significance of this solution?
According to Ocuphire’s CEO George Magrath, MD, MBA, MS, PS has the potential to become the “first commercial treatment for patients who have undergone LASIK surgery and experience low light visual disturbances.”
And when can we expect data?
While the trial is slated to conclude by November 2025, key your eyes out for updates in the meantime!