Nyxol

Nyxol® Eye Drops

Beginning Phase 3 Development Through the 505(b)(2) Pathway

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. At Ocuphire, we believe that the results from Nyxol’s three Phase 1 and four Phase 2 trials totaling over 230 patients support its current development plan.

Phentolamine mesylate is also the active pharmaceutical ingredient in two FDA-approved drugs, REGITINE® and OraVerse®. Nyxol® is being developed under the 505(b)(2) pathway.

Nyxol: Phentolamine Ophthalmic Solution

Nyxol is preservative free and EDTA free. Chronic daily dosing of Nyxol before bedtime has demonstrated no significant daytime redness and durability of effects more than 24 hours.

Comparison Graphic
Product Candidate Indication Development Stage Anticipated Milestones
Preclinical Phase 1 Phase 2 Phase 3

Ocuphire-Focused Development

Nyxol® Eye Drops Dim Light or Night Vision Disturbances (DLD)
Preclinical complete
Phase 1 complete
Phase 2 in progress
Phase 3 not started
Initiate Phase 3 LYNX-1 trial 4Q2020 Data expected in 3Q21 (n=160)
Nyxol® Eye Drops Reversal of Mydriasis (RM)
Preclinical complete
Phase 1 complete
Phase 2 in progress
Phase 3 not started
Initiate Phase 3 MIRA-2 trial 4Q2020 Data expected in 1Q21 (n=168)
Nyxol® + Low-Dose Pilocarpine Eye Drops Presbyopia
Preclinical complete
Phase 1 in progress
Phase 2 not started
Phase 3 not started
Initiate Phase 2 VEGA-1 trial 1Q2021; Data expected in 2Q21 (n=152)

Partnering-Focused Development

Combo (Nyxol®+Latanoprost) Eye Drops Glaucoma
Preclinical complete
Phase 1 complete
Phase 2 in progress
Phase 3 not started
Next Steps: 2nd line add-on Phase 2 trial (with partner funding)

Multiple Indications with Large Market Potential

Nyxol is currently being developed for dim light and night vision disturbances (DLD), reversal of mydriasis, and presbyopia. Each indication has a precedent pathway to approval or primary endpoints discussed with the FDA. Nyxol is an investigational drug candidate that is being tested in clinical trials and has not yet been approved by the FDA or other regulatory bodies for commercial sale.

Night Vision Disturbances

About Dim Light or Night Vision Disturbances

Dim light or night vision disturbances (DLD or NVD) is a new indication with no approved therapies, despite an estimated 15-20 million people in the United States with moderate-to-severe DLD and an addressable DLD market of approximately 4 million U.S. adults.

Vision at night or in dim light conditions is different from daytime vision in several important ways. Most notably, at night, the pupils dilate to allow more light into the eye. Because of this dilation, light also passes through the periphery of the cornea and lens. Any imperfections or aberrations present on the periphery cause light to reach the retina in a non-focused and scattered way, creating glare, halos, starbursts, ghosting and a loss of contrast sensitivity (CS).

Individuals with peripheral imperfections or aberrations experience glare and streaky vision, as well as a “halo” or “starburst” effect. These visual disturbances can be debilitating to a variety of everyday activities, especially driving. The light emitted by traffic lights and other cars scatters and obscures most of the visual field, making driving in dim light conditions hazardous.

Diminished night vision is a natural part of aging as well as a common side effect of several conditions and procedures. Night vision disturbances are induced by a variety of causes, including night myopia, cortical cataracts, post-intraocular lens (IOL) implants, LASIK, and keratoconus.

Market Landscape

38M

Adults suffering from Dim Light or Night Vision Disturbances in the U.S.

How Nyxol Can Help DLD

The effects of DLD can be reduced or eliminated by reducing the pupil size to a diameter that prevents the scattering effect without impeding the ability to see at night. Nyxol has the potential to be a first-line treatment for night vision disturbances based on its optimal “moderate” pupil reduction properties. In clinical trials, Nyxol® demonstrated improvement in contrast sensitivity and visual performance at night and during the day.

"That would be helpful, especially for younger people who tend to need to drive at night more!"

— Physician survey respondent

"There’ll be a big group of patients who say "well I can’t afford surgery right now", I would give them this product without a doubt."

— Physician KOL

"It seems like a simple process with really no side effects"

— Cataract respondent, aged 62

"Once theres a drug and a category, that’s when they start looking for the disease."

— Physician KOL

Clinical Trials

ORION-1 (NCT03960866), a recently completed multi-center, randomized, double-masked, placebo-controlled, multiple-dose Phase 2b study with evening dosing, demonstrated statistically significant reductions in pupil diameter, which was sustained through 36 hours post-dose. For more information about our previously completed Phase 2 studies on night vision disturbances, please visit clinicaltrials.gov (NCT04004507, NCT01703559). 

Phase 2 Clinical Trial of Nyxol in Elderly Subjects with Glaucoma

Severe Night Vision Disturbance Single-Dose Phase 2 Clinical Trial with Nyxol

Night Vision Complaints Multiple-Dose Phase 2 Clinical Trial with Nyxol

Building on these results, we plan to launch Phase 3 study LYNX-1 in the second half of 2020.

Reversal of Pharmacologically Induced Mydriasis

About Reversal of Pharmacologically Induced Mydriasis

An estimated 200 million comprehensive eye exams take place globally each year, including 80 million in the United States. Most involve pharmacologically induced dilation (or mydriasis) of the pupils. In addition, 4 million eyes are dilated for surgical procedures.

Side effects of mydriasis include sensitivity to light and blurred vision, which make it difficult to read, work, and drive. Also, many drops cause cycloplegia, the temporary paralysis of the muscle which allows the eye to focus on near objects. For this reason, many patients may request to avoid dilation, limiting the eye care provider’s ability to conduct a comprehensive exam.

Pharmacological mydriasis is achieved either by stimulating the iris dilator muscle with the use of alpha adrenergic agonists (e.g., phenylephrine), or by blocking the iris sphincter muscle with the use of muscarinic antagonists (e.g., tropicamide), or a combination of both mydriatic agents. Such pharmacologically-induced mydriasis can last from a few hours (typically 6 hours) up to 24 hours, depending on the pigmentation of the iris, one’s age, and other factors.

There are no drugs currently approved for the reversal of mydriasis. Dapiprazole, an alpha-1 antagonist, was approved by the FDA in 1990 to reverse pharmacologically-induced mydriasis and was marketed under the trade name Rev-Eyes. According to the FDA, Rev-Eyes was discontinued from the market for reasons other than safety and efficacy.

Market Landscape

100M

In-office eye dilations per year in the U.S.

How Nyxol Can Help Pharmacologically Induced Mydriasis

Nyxol alone has shown in multiple Phase 2 trials the ability to reduce pupil size by relaxing the iris dilator muscle in normal eyes. To counteract mydriatic drugs, Nyxol could be instilled in the eyes to more rapidly reverse mydriasis, thereby potentially relieving post-exam side effects, visual impairment, eye strain and discomfort.

"The sunlight hurts my eyes, my eyes water. I can’t see to drive home."

— RM Patient, Aged 71

"I have to stay indoors. They say it only lasts a few hours but it lasts all day it is very annoying.” "

— RM Patient, Aged 51

Clinical Trial

MIRA-1 (NCT04024891) Phase 2b results showed statistically significant reductions in pupil diameter (PD) at 1 hour, 2 hours, and 4 hours post-treatment compared to placebo. Nyxol also returned more subjects to baseline vision (accommodation) and PD within 2 hours compared to placebo.

Mira-2: Reversal of Mydriasis Phase 3 Clinical Trial for Nyxol

Building on these results, we plan to launch the Phase 3 MIRA-2 study in the second half of 2020

Presbyopia

About Presbyopia

Presbyopia is an age-related condition that commonly appears in people over 40 years old. As the eye ages, loss of lens elasticity results in an inability to focus on nearby objects (farsightedness). Because of the ubiquity of the condition, presbyopia represents a large market both in the United States and abroad, totaling over 2 billion presbyopia patients. 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.

Individuals with presbyopia use reading glasses and contact lenses, and in some cases receive surgical interventions, but there are no currently approved drug therapies for presbyopia. There are several drawbacks to reading glasses. For example, presbyopia only affects near vision, so reading glasses must be put on and taken off throughout the day. Contact lenses for presbyopia can cause eye strain, night vision disturbances, and other side effects. Eye drops are considered to be the “holy grail” alternative to corrective devices for presbyopia.

Market Landscape

120M

in the US. Expected to grow to 150+M by 2034

How Nyxol Can Help Presbyopia

Presbyopia is a large unmet market, where pupil modulation is a clinical development area of focus. In previous clinical trials, Nyxol alone demonstrated the ability to moderately reduce pupil diameter and improve near visual acuity. Further decreasing the pupil size with Nyxol combined with a low-dose miotic agent may achieve the “pinhole effect” that results in improved depth of focus and improved near reading vision.

"Who would not do this? This would just become part of my daily routine for my eyes to be able to see things up close. How convenient is that?"

— Presbyopia patient, aged 49

"The drops would help me enjoy cooking recipes, reading magazines and independent shopping at food store."

— Presbyopia patient, aged 65

Clinical Trial

In ORION-1 (NCT03960866), a recently completed Phase 2b study, Nyxol as a single agent showed statistically significant improvement of 1 or more lines from baseline in near visual acuity, with a trend of 2 or more lines of improvement at multiple time points.

Phase 2 Clinical Trial of Nyxol in Elderly Subjects with Glaucoma

We plan to begin the Phase 2 study VEGA-1, which will study the effects of 1% Nyxol with a low dose miotic in presbyopia, in the first quarter of 2021.

Glaucoma

About Glaucoma

Glaucoma is a progressive, age-related disease and the leading cause of irreversible vision loss, affecting 60 million people worldwide, including 3 million people in the United States. Glaucoma is the result of increased intraocular pressure (IOP) due to a buildup of aqueous humor in the eye. Sustained elevated IOP damages the optic nerve, resulting in loss of vision and blindness. There are currently five classes of approved glaucoma medications, yet almost half of patients in treatment for glaucoma do not reach normal IOP goals. Second-line treatments, especially for patients in normotensive range, are needed to decrease patients’ IOP levels.

Market Landscape

3M

U.S. prevalence

Clinical Trial

In NYX-01a2 (NCT01703559), a Phase 2 DLD study with subjects with normal IOP baseline, a single dose of 1% Nyxol resulted in a statistically significant lowering of IOP.

Night Vision Complaints Multiple-Dose Phase 2 Clinical Trial with Nyxol

Phase 2 Clinical Trial of Nyxol in Elderly Subjects with Glaucoma

At this time, we are only planning to evaluate Nyxol as a second-line add-on to standard of care in glaucoma with a partner.

Read Our Posters & Publications

We are dedicated to publishing the results of Nyxol studies in peer-reviewed medical journals.

Browse Posters & Publications