Nyxol® is a preservative-free ophthalmic solution containing 0.75% phentolamine (or 1% phentolamine mesylate), a nonselective alpha adrenergic antagonist that inhibits the contraction of smooth muscle of the iris.
In multiple Phase 2 trials Nyxol reduced pupil diameter, resulting in better contrast sensitivity and visual acuity. Nyxol is being developed for dim or night vision disturbances (DLD), reversal of pharmacologically-induced mydriasis, and presbyopia.
Presbyopia is an age-related condition with onset most common in people over 40 years old. As the eye ages, the lens becomes stiffer, which limits the eye’s ability to adjust its focus for reading or for other tasks that require clear vision at near distances.
It is estimated that 120 million Americans have presbyopia and this number is expected to grow as the population above the age of 45 increases.
Currently, there are no pharmacological therapies approved for presbyopia, but there is evidence that decreasing pupil diameter, especially to a size of 1.6 mm to 2.0 mm to create a “pinhole” effect, can improve near visual acuity by increasing the depth of focus.
Ocuphire Pharma, Inc., a clinical-stage ophthalmic biopharmaceutical company focused on developing and commercializing therapies for the treatment of several eye disorders, recently announced that it has enrolled the first patients in a Phase 2 proof of concept trial, titled VEGA-1, to evaluate a combination kit of Nyxol and low-dose pilocarpine in presbyopia.
Over 12 sites representing a majority of the planned clinical sites are activated and recruiting patients. Nyxol’s potential to improve near vision is based on its mechanism of reducing pupil diameter which results in an increased depth of focus.
Nyxol alone in multiple Phase 2 trials has reduced pupil diameter by approximately 20% and has significantly improved near visual acuity by one eye-chart line for over 24 hours after an evening eye drop.
It has been well established by the field that reducing pupil diameter to the 1.6 to 2.0 mm range (“pinhole effect”) can lead to significant improvements in near vision for presbyopic patients. Nyxol is being evaluated as part of a two-drug kit provided to patients, with Nyxol to be applied once daily in the evening and low-dose pilocarpine to be dosed in the daytime.
According to a market research report by GlobalData, 40% of patients would request an alternative to reading glasses if available and 69% of patients would consider an eye drop alternative.
Some key factors that will influence patient adoption will be efficacy, tolerability, comfort, onset of action, durability, and good distance vision.
Mina Sooch, MBA, President and CEO of Ocuphire Pharma commented, “Presbyopia could be one of the largest patient populations at over 100 million to be treated with a pharmacologic option. Many people with presbyopia may greatly benefit from an eye drop treatment as an alternative to reading glasses. We believe that the combination of Nyxol and low-dose pilocarpine has an ideal product profile to become a promising treatment for presbyopia. We are pleased to begin enrollment in the VEGA-1 clinical trial working with our CRO partner Oculos and look forward to reporting results at the end of the second quarter this year. This is our 3rd later stage clinical trial launched for Nyxol in just the last few months.”
“I am very happy to see that the VEGA-1 trial has begun enrollment, which brings the potential for Nyxol and low-dose pilocarpine eye drops to allow presbyopia patients to experience the ability to see both at near and at distance without the dependence on reading glasses. The combination of Nyxol moderately inhibiting the iris dilator muscle and low dose of pilocarpine, an extensively studied miotic, moderately activating the iris constrictor muscle should allow for unopposed pupil constriction to reach the ‘pin-hole’.
Ocuphire’s use of agents working on both iris muscles to manage pupil size is a key differentiating factor for its approach,” says Dr. Marguerite McDonald, Clinical Professor of Ophthalmology at the NYU Langone Medical Center.
VEGA-1 is a double-masked, randomized, placebo-controlled, multi-center trial designed to evaluate 0.75% Nyxol in combination with low dose (0.4%) pilocarpine for treatment of presbyopia. The trial is expected to enroll approximately 152 patients with a clinical diagnosis of presbyopia (near visual acuity of 20/50 or worse).
The primary endpoint is percentage of patients with at least 3 lines (15 letters or more) of binocular distance corrected near visual acuity (DCNVA) improvement on a standard near vision eye chart in daytime (photopic) lighting conditions.
Secondary endpoints at multiple timepoints include improvements in 3 lines of DCNVA without any loss of distance vision, pupil diameter, and improvements in DCNVA at 1 and 2 lines compared to placebo as well as to each Nyxol and low-dose pilocarpine alone.