Ocuphire Pharma, Inc. announced the enrollment of the first subject in the LYNX-2 Phase 3 registration study evaluating phentolamine ophthalmic solution 0.75% (PS) for the treatment of decreased visual acuity under low (mesopic) light conditions following keratorefractive surgery.
The LYNX-2 trial is being conducted under conditions of a Special Protocol Assessment (SPA) with the U.S. Food and Drug Administration (FDA).
As previously announced, Ocuphire received written agreement from the FDA that the clinical trial protocol and planned statistical analysis of the LYNX-2 phase 3 trial would adequately address objectives supporting regulatory submission and a potential future marketing application in this indication.
“We are pleased to begin enrollment in the LYNX-2 study of PS,” said George Magrath, MD, MBA, MS, CEO of Ocuphire. “If our registration program meets expectations, and PS is subsequently approved by the FDA, it could potentially be the first commercial treatment for patients who have undergone LASIK surgery and experience low light visual disturbances. We believe that PS is a product with broad potential applications in ophthalmology. Having already received approval for RYZUMVI to treat pharmacologically-induced mydriasis, our partner Viatris, Inc. (Viatris) now has the opportunity to create further value as it pursues additional indications for PS, which also include presbyopia.”
Vision disturbances under low light conditions are characterized by peripheral corneal imperfections (aberrations) that result in unfocused light when the pupil dilates under low light conditions. Patients experience decreased low contrast visual acuity as well as glare, halos and starbursts.
Patients undergoing keratorefractive surgery (including LASIK, PRK, SMILE, and RK) have been identified as one of the major sub-populations affected, the others being those who have night myopia (naturally occurring), non-central cortical cataracts, keratoconus or post-multifocal or extended depth of focus intraocular lens (IOL) implantation.
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, PS eye drops have the potential to be a treatment option that could improve patients’ ability to see and function in low light.
The previous LYNX-1 phase 3 study evaluating PS successfully met its primary endpoint, with 13% of subjects gaining 15 or more ETDRS letters of mesopic low contrast distance visual acuity at Day 8 vs. 3% on placebo (p<0.05). PS is manufactured as a preservative-free eye drop, which potentially allows for continued use while avoiding the common side effects of preservatives, such as ocular surface damage, eye irritation and tear film instability.
For more information about the prior LYNX-1 Phase 3 study evaluating PS, please visit https://www.ocuphire.com/news-media/press-releases/detail/374/ocuphire-announces-positive-topline-results-from-lynx-1.
Jay Pepose, MD, PhD, chief medical advisor at Ocuphire, commented, “Low light vision disturbances are characterized by difficulty in distinguishing objects with subtle differences in contrast, such as a pedestrian in a crosswalk at dusk or on a rainy day under low light conditions. This represents a significant, yet often overlooked sequela of LASIK or other forms of keratorefractive surgery. Despite the success and popularity of LASIK for vision correction, a subset of patients find themselves grappling with these low light or night-time vision challenges, for which there has been no specific, targeted treatment available. If approved, PS offers the potential to enhance visual performance in low light conditions and restore a sense of normalcy and confidence in these patients.”
Ocuphire has a global license agreement with Viatris to co-develop and commercialize PS for the reversal of mydriasis, presbyopia and low light vision disturbances. Under the terms of this agreement, the two companies agreed to co-develop the product for each of these conditions, with Viatris providing funding for development of these programs. Further, Ocuphire is eligible to receive specified regulatory or net sales milestone payments associated with these indications as well as royalties on commercial sales. In September 2023, Ocuphire met the $10 million milestone payment requirements attributed to the FDA’s approval of PS for reversal of mydriasis.
LYNX-2 Design
LYNX-2 is a randomized, double-masked, placebo-controlled phase 3 registration study designed to evaluate the safety and efficacy of PS compared to placebo in subjects who underwent keratorefractive surgery and then reported decreased visual acuity under low light conditions. The trial is expected to enroll 200 subjects.
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. Additional information about the Phase 3 trial can be found at www.clinicaltrials.gov.