Nyxol

Indications for Nyxol

We are focused on developing therapies to help patients with a variety of ophthalmic disorders. Our leading drug candidate, Nyxol® eye drops, a once-daily ophthalmic solution containing phentolamine mesylate, is currently being developed for glaucoma, night vision disturbances (NVDs), presbyopia and mydriasis. Each indication has a precedent pathway to approval or primary endpoint agreed with the U.S. FDA. Nyxol® is an investigational drug candidate that is testing in clinical trials and has not yet been approved by the FDA or other regulatory bodies for commercial sale.

 

Night Vision Disturbances

Night Vision Disturbances (NVDs) is a new indication being pioneered by Ocuphire and has no approved therapies despite an estimated 4 million people in the United States and 7 million worldwide (Europe and Japan) affected by the condition. In dim-light conditions, pupils dilate to allow more light to enter the eye. However, because of this dilation, light also passes through the periphery of the cornea and lens. As light passes through the periphery of the eye, any imperfections or aberrations cause light to scatter before it reaches the retina. Individuals with peripheral imperfections or aberrations experience glare and streaky vision, as well as a “halo” or “starburst” effect.

Night vision disturbances are induced by a variety of causes, including night myopia, cortical cataracts, post-IOL implants, Lasik and keratoconus. NVDs can be debilitating and interfere with a variety of everyday activities, most notably driving. The light emitted by traffic signals and other cars makes driving in dim-light conditions difficult and unsafe. The effects of NVDs can be reduced or eliminated by reducing pupil size to a smaller diameter that prevents the scattering effect without impeding the ability to see at night.

Nyxol could be a first in line treatment for night vision disturbances based on its optimal pupil reduction properties and consequent improvement in contrast sensitivity and visual performance at night and during the day. Nyxol’s alpha-1 blocking activity relaxes (inhibits contraction of) the iris dilator muscle, resulting in a smaller pupil size.

Glaucoma

Glaucoma is a progressive disease with age and the leading cause of irreversible vision loss, affection 3 million people in the United States and a total of 60 million people worldwide. Glaucoma is the result of increased intraocular pressure (IOP) due to a buildup of aqueous humor in the eye.  Sustained elevated intraocular pressure damages the optic nerve, resulting in loss of vision and blindness.

There are currently different classes of approved glaucoma medications ($3B spent in the US), but almost half of the glaucoma patients on treatment do not reach normal eye pressure goals. Additive treatments with new mechanisms to the standard of care glaucoma drugs are needed to decrease the very high IOP levels. Further, glaucoma is asymptomatic until the optic nerve sustains damage, and the required multiple daily applications and adverse effects associated with glaucoma treatments often result in missed doses or noncompliance. The significant systemic safety and topical tolerability issues add to the noncompliance.

Nyxol could be an ideal complement to polypharmacy treatment of glaucoma given its IOP lowering, all-day effect, and improved vision performance. Nyxol uniquely works across multiple IOP lowering pathways.The major conventional outflow pathway includes the trabecular meshwork (TM), a tissue with contractile properties and α2 adrenergic receptors. It is well accepted that relaxing of the TM is the optimal IOP lowering solution. Literature supports both α1 & α2 agonists contract the TM, thus the non-selective α blocker Nyxol is likely to relax the TM and lower IOP via this major outflow pathway.  The second outflow mechanism includes the uveoscleral pathway where it is established that blocking the α1 receptors increases uveoscleral outflow. Further, Nyxol is highly lipophilic, allowing depot uveal pigment absorption for greater and long-lasting efficacy.

Presbyopia

Presbyopia is an age-related condition that commonly appears in people aged 40-50. As the eye ages, loss of lens elasticity results in an inability to focus on near objects. Presbyopia is a nearly-ubiquitous condition that comes with age and affects over 100 million people in the United States alone and close to 2 billion worldwide. Like glaucoma, presbyopia is expected to increase in prevalence as the average age of the population increases over time. Individuals with presbyopia use reading glasses, contact lenses, and in some cases, surgical interventions, but there are no currently approved drug therapies for presbyopia.

There are numerous well-known and intuitive drawbacks to reading glasses. For example, presbyopia only affects near vision, reading glasses must be removed and reapplied constantly throughout the day. Contact lenses for presbyopia pose their own unique challenges of eye strain, night vision disturbances, and other negative side effects. Eye drops are considered the ‘holy grail’ alternative to corrective devices for this aging condition.

Presbyopia is a large unmet market, where pupil aperture management such as Nyxol’s approach is an intense area of focus. Nyxol is a potential treatment alone or in combination for presbyopia based on its ability to reduce pupil diameter and improve visual acuity. The goal is to achieve a target pinhole size, which will result in clear near vision.

Nyxol Product Profile

In Summary, Nyxol once-daily drops are an investigational 505(b)(2) ophthalmic solution containing phentolamine mesylate, a reversible non-selective alpha 1 and 2 adrenergic blocker. Nyxol has been tested in 114 subjects over the course of five randomized, double-masked, placebo-controlled Phase 1 and 2 studies, demonstrating promising evidence of efficacy, safety, and tolerability, relevant to our targeted indications. Phentolamine mesylate was previously approved as an IV formulation for lowering blood pressure in pheochromocytoma and an intramuscular formulation for speedy recovery from dental anesthesia in the United States and was shown to be tolerable and efficacious.

We believe that Nyxol possesses a differentiated product profile compared to other therapies on the market and in clinical development. Nyxol’s safety and tolerability, as well as its novel mechanism of action, make it an ideal candidate for polypharmacy uniquely addressing the cross-section of indications. If approved, clinicians could utilize Nyxol as either a first-line intervention or as adjunct therapy for patients in need of further improvement. Nyxol’s ability to improve both daytime and night vision would also help mitigate the adverse side effects of other treatments with the convenience of once-daily dosing.

 

Publications/Presentations

Ocuphire Pharma is dedicated publish the results of its Nyxol studies in peer review medical literature and/or present them at leading eye care congresses around the world. Nyxol’s pharmaceutical active ingredient, phentolamine mesylate, which falls in the alpha adrenergic antagonist class, has a long literature history.

List of key papers or presentations are cited below. If company presentation, copies are available below.

Holladay JT, Pitlick W, Meyer AR. Phentolamine Mesylate Ophthalmic Solution Once Daily Reduces Pupil Diameter and Improves Night Vision Disturbances.  AAO Abstracts PA025, 2018.  Presented at the #  American Association of  Ophthalmology, Chicago, IL (Read more)
Marguerite McDonald et al., Phentolamine Mesylate Treatment of Severe Night Vision Complaints, AAO Abstracts, Chicago, IL, 2010, PO433. (Read more)

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