Published in Pipeline

Ocuphire Pharma initiates VEGA-3 phase 3 trial evaluating phentolamine ophthalmic solution 0.75% for presbyopia

Top-line data from VEGA-3 phase 3 trial expected in first half of 2025

Top-line data from LYNX-2 phase 3 trial in patients with decreased visual acuity under low light conditions following keratorefractive surgery expected in first quarter of 2025

Ocuphire Pharma, Inc. (Nasdaq: OCUP), a clinical-stage ophthalmic biopharmaceutical company focused on developing and commercializing small-molecule therapies for the treatment of patients with retinal and refractive eye disorders, today announced that the VEGA-3 phase 3 clinical trial evaluating phentolamine ophthalmic solution 0.75% for presbyopia has dosed its first participants.

Presbyopia, the gradual loss of ability to focus on near objects, typically becomes noticeable in the early to mid-40s. This progressive and ubiquitous condition leads to the widespread use of reading glasses or bifocals. Phentolamine ophthalmic solution 0.75% is being developed to provide a non-invasive, convenient alternative to traditional corrective measures.

“Our goal is to provide a safe, long-lasting, effective solution that restores near vision and enhances overall visual performance in people with presbyopia, under both daytime and nighttime conditions,” said George Magrath, MD, MBA, MS, Ocuphire’s CEO. “We are pleased to begin the VEGA-3 trial, building on the positive results generated in our prior presbyopia studies, which have shown a rapid onset of action, favorable safety profile, and sustained duration of effect that are promising at this stage.”

Ocuphire anticipates using data obtained from the VEGA-3 trial demonstrating the efficacy and safety of Phentolamine Ophthalmic Solution 0.75% as a potential treatment for presbyopia to support a supplemental New Drug Application with the U.S. Food and Drug Administration (the “FDA”).

Dr. Magrath continued, “We are also excited about the continued enrollment in the LYNX-2 trial. Our top-line data for LYNX-2 are expected in the first quarter of 2025, assuming enrollment continues at the current rate. I’m very proud of the work our team and partners have put into the execution of this study.”

VEGA-3 phase 3 pivotal trial design

VEGA-3 is a randomized, double-masked, placebo-controlled, multi-center, phase 3 clinical trial evaluating phentolamine ophthalmic solution 0.75% in 545 participants with presbyopia. Participants are randomized 3:2 to receive one drop of phentolamine ophthalmic solution 0.75% or placebo each evening. The primary endpoint is the percentage of participants with 15-letter improvement in photopic binocular distance-corrected near visual acuity (“DCNVA”) on the eighth day following their first visit. The improvement in binocular DCNVA for each participant will be relative to their own baseline value. Participants will be followed a total of 48 weeks to collect chronic safety data. Recruitment will take place at up to 40 investigational sites in the U.S. For more information on the trial design and endpoints, please refer to www.ClinicalTrials.gov (NCT06542497).

Top line data from LYNX-2 phase 3 study expected Q1 2025

The LYNX-2 phase 3 trial is a randomized, double-masked, placebo-controlled phase 3 registration trial designed to evaluate the safety and efficacy of phentolamine ophthalmic solution 0.75% compared to placebo in participants who underwent keratorefractive surgery and then reported glare, halos or starbursts and demonstrated low contrast visual acuity under mesopic (low) light conditions.

The LYNX-2 trial is being conducted under conditions of a Special Protocol Assessment (SPA) with the FDA. The trial is expected to enroll 200 participants. The primary endpoint, agreed with the FDA under the SPA, will be a gain of 3 lines (or 15 letters) or more of distance vision improvement on a low contrast chart in low light conditions after 15 days of dosing. Top line data are expected in the first quarter of 2025. Additional information about the LYNX-2 phase 3 trial can be found at www.ClinicalTrials.gov (NCT06349759).

There are currently no FDA-approved treatments for visual disturbances under low light conditions. With a mechanism of action that moderately reduces pupil size without the increased risks of retinal tears or detachment associated with parasympathomimetic miotics that engage the ciliary muscle, Phentolamine Ophthalmic Solution 0.75% eye drops have the potential to be a treatment option that could improve patients’ ability to see and function in low light following keratorefractive surgery.

Ocuphire is responsible for managing the VEGA-3 and LYNX-2 trials. Under the terms of the License Agreement, Ocuphire’s partner will reimburse Ocuphire for agreed-to budgeted costs related to the development of Phentolamine ophthalmic solution 0.75% through FDA approval, and then share costs above an agreed upon threshold amount.

About phentolamine ophthalmic solution 0.75%

Phentolamine ophthalmic solution 0.75%, Ocuphire’s late-stage product candidate, is a non-selective alpha-1 and alpha-2 adrenergic antagonist designed to reduce pupil size. It works by uniquely blocking the alpha-1 receptors found on the radial iris dilator muscles, which are activated by the alpha-1 adrenergic receptors, without affecting the ciliary muscle.

Phentolamine ophthalmic solution 0.75% is being developed for presbyopia and dim (mesopic) light vision disturbances (sometimes referred to as DLD) after keratorefractive surgery. Phase 2 and phase 3 trials for the use of Phentolamine Ophthalmic Solution 0.75% to treat presbyopia have met their primary endpoints.