Ocuphire Pharma, Inc. announced the initiation of its latest clinical trial evaluating phentolamine ophthalmic solution (POS) 0.75% for presbyopia: the phase 3 VEGA-3 study.
First, talk about phentolamine.
Designed with a preservative-free formulation, the active ingredient—phentolamine—is a non-selective alpha-1 and alpha-2 adrenergic antagonist that is known to enhance the antimicrobial properties of macrolide antibiotics against Gram-negative bacteria.
How POS 0.75% works: The solution reversibly binds the alpha-1 adrenergic receptors located on the iris dilator muscle, resulting in a potential reduction in pupil diameter without impacting the ciliary muscle.
- Note: Pupil dilation is primarily controlled by the radial iris dilator muscles around the pupil, which can then be activated by the alpha-1 adrenergic receptors.
It’s not just being studied for presbyopia, right?
That’s correct! In partnership with Viatris, Inc., the formulation is also currently in clinical development for night vision disturbances (NVD), i.e., decreased visual acuity (VA) under low (mesopic) light conditions post-keratorefractive surgery.
- Clinical update: The ongoing phase 3 LYNX-2 trial was initiated on April 2024
- Topline data expected Q1 2025
Wasn’t it FDA-approved as well?
Yup! The FDA approved POS 0.75% in September 2023 under the brand name RYZUMVI for treating the reversal of mydriasis (RM) —and subsequently was commercially launched in April 2024.
Gotcha. So what has clinical data shown so far?
Phentolamine was previously studied in the phase 2 VEGA-1 (NCT04675151) study.
The details: POS 0.75% was analyzed as a stand-alone treatment and in combination with low-dose (0.4%) pilocarpine (LDP) in 320 participants (aged 40 to 64) diagnosed with presbyopia.
- Those findings: POS 0.75% administered alone and in combo with LDP resulted in:
- Moderately reduced pupil diameter
- Sustained an 18-hour duration of efficacy
What about the VEGA-2 study?
That phase 3 pivotal trial (NCT05646719)—a randomized, double-masked, placebo-controlled, multicenter study—also evaluated POS 0.75% when administered alone and in combo with LDP 0.4% for 333 presbyopia patients (aged 40 to 64).
- Those findings: While the study concluded in October 2023, Ocuphire has not yet reported outcomes.
Now moving on to this VEGA-3 study.
Designed as a randomized, double-masked, placebo-controlled, multicenter phase 3 trial (NCT06542497), VEGA-3 is expected to enroll an estimated 545 patients (aged 45 to 64) diagnosed with presbyopia.
- Participant criteria: See here
- The design: Patients are being randomized 3:2 to receive either of the following every evening:
- POS 0.75% (one drop)
- Placebo solution (one drop)
- Duration: Eight days
- Note: Patients will be followed for a total of 48 weeks at up to 40 U.S. clinic locations
What’s being measured?
The primary outcome measure includes the primary efficacy endpoint at Day 8.
Specifically: This includes the percentage of participants with ≥ 15 letters of improvement in binocular DCNVA and with < 5 letters of loss in binocular distance-corrected visual acuity (BCDVA) from baseline, and comparing POS 0.75%-treated participants to placebo-treated participants at 12 hours post-dose at Visit 4.
And when is data expected from this?
Clinical Trials estimates the study will conclude in June 2026—so keep an eye out for interim data in the meantime.
Then what?
Pending positive clinical outcomes, Ocuphire intends to use the data to support a supplemental new drug application (NDA) submission to the FDA.