Reversal of Pharmacologically Induced Mydriasis
About Reversal of Pharmacologically Induced Mydriasis
In the United States, an estimated 100 million comprehensive eye exams take place each year that involve pharmacologically induced dilation (or mydriasis) of the pupils.
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.
In-office eye dilations per year in the U.S.
How Nyxol Can Help Pharmacologically Induced Mydriasis
Across multiple clinical trials, Nyxol alone has shown 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, Age 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, Age 51
Building on the results of MIRA-1 and MIRA-2, we have launched a second Phase 3 registration trial (MIRA-3) and a Pediatric safety study (MIRA-4) in the fourth quarter of 2021 with data from both studies expected near the end of Q1 2022.
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 (NCT04620213) and MIRA-3 (NCT05134974) both Phase 3 studies met their primary endpoint at 90 minutes and multiple secondary endpoints. Effect was seen starting at 1 hour and lasting up to 24 hours. Nyxol demonstrated a faster return to baseline compared to placebo at 90 minutes and accommodation and shortened recovery time from dilation on average by 4 hours.
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 128 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.
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. Two labels are being pursued for presbyopia: Nyxol alone and Nyxol with low-dose (0.4%) pilocarpine. 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, Age 49
"The drops would help me enjoy cooking recipes, reading magazines and independent shopping at food store."— Presbyopia patient, Age 65
VEGA-1 (NCT04675151), a Phase 2 study met its primary endpoint and several key secondary endpoints. Nyxol+LDP combination treatment showed statistically significant improvement in 3-lines or more from baseline in near visual acuity at multiple timepoints.
In ORION-1 (NCT03960866), a 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.
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 16 million people in the United States with moderate-to-severe DLD.
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.
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, Age 62
"Once theres a drug and a category, that’s when they start looking for the disease."— Physician KOL
ORION-1 (NCT03960866), a recently completed multi-center, randomized, double-masked, placebo-controlled, multiple-dose Phase 2b study with evening dosing, met the primary endpoint and demonstrated statistically significant reductions in pupil diameter, which was sustained through 36 hours post-dose.
Phase 2 Clinical Trial of Nyxol in Elderly Subjects with Glaucoma (NCT03960866)
Severe Night Vision Disturbance Single-Dose Phase 2 Clinical Trial with Nyxol (NCT04004507)
Night Vision Complaints Multiple-Dose Phase 2 Clinical Trial with Nyxol (NCT01703559)
Building on these results, we have launched the Phase 3 study LYNX-1 in the second half of 2020. (NCT04638660)
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.
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.