Ocuphire Announces Enrollment of First Patients in Second Phase 3 Pivotal Trial (MIRA-3) for Nyxol in Reversal of Mydriasis
Ocuphire Pharma announced that the first subjects have been enrolled in the MIRA-3 phase 3 pivotal trial evaluating Nyxol eye drops in the reversal of pharmacologically-induced mydriasis (dilation of the pupil). With 6 sites enrolling subjects within days of activation and 10 more sites expected to start screening shortly, topline results from the MIRA-3 trial are expected in early 2022 (around the end of the first quarter).
“The safety and efficacy of Nyxol for reversal of mydriasis have been demonstrated in our prior MIRA-1 phase 2b and MIRA-2 phase 3 clinical trials,” Mina Sooch, President and CEO of Ocuphire Pharma, said in a company news release. “Both of these trials successfully met their primary and multiple secondary endpoints with statistical significance. We know that more than half of patients take 6 hours or longer, sometimes 24 hours, to return to their normal pre-dilated pupil size. Our prior data on Nyxol showed that 50% of patients returned to baseline by 90 minutes and 80% by 3 hours. A positive outcome in MIRA-3 comparable to the results achieved in MIRA-2 will position us to submit an NDA for Nyxol for reversal of mydriasis in late 2022. Successful completion of MIRA-3, as well as our planned smaller pediatric safety study, will bring the total number of patients treated with Nyxol to more than 500, out of more than 900 study subjects.”
David Boyer, MD, Vitreoretinal Surgeon, Retina-Vitreous Associates Medical Group commented, “Providing the best care to my patients is my top priority. Therefore, I am eager to adopt treatments that enhance the patient experience. As a retinal specialist, there is simply no substitute for dilation when it comes to disease management and treatment, including chronic intravitreal injections for wet AMD or DME. With the ability to return many patients safely to baseline pupil diameter within an hour or two, Nyxol can provide substantial benefit. We dilate almost all of our patients, and I would be excited to offer Nyxol to my patients following dilation in order to optimize their care.”
MIRA-3 Trial Design for Nyxol
Nyxol is a proprietary, preservative-free, ophthalmic formulation of phentolamine mesylate designed to reduce pupil size by inhibiting or relaxing the iris dilator muscle. MIRA-3 is a multicenter, randomized, parallel-arm, double-masked, placebo-controlled study of the safety and efficacy of Nyxol (0.75% phentolamine ophthalmic solution) to reverse pharmacologically-induced mydriasis in healthy subjects. The MIRA-3 trial is designed to enroll approximately 330 subjects aged 12 and older. After screening, eligible subjects are randomized 2:1 to one of the 2 treatment arms (Nyxol or placebo, respectively) and will receive 1 of 3 approved mydriatic agents approximately 1 hour prior to receiving study treatment drops. Randomization will be 3:1:1 to a mydriatic agent (2.5% phenylephrine, 1% tropicamide, or Paremyd, respectively). The primary efficacy endpoint is the percentage of subjects’ study eyes returning to ≤ 0.2 mm from baseline photopic pupil diameter at 90 minutes. Secondary endpoints include pupil diameter (at multiple time points from 30 minutes to 24 hours), accommodation, and a patient questionnaire, as well as new assessments of glare disability, glare tolerability, and pupillary response to light.
Ocuphire is collaborating closely on the Nyxol programs with a leading clinical research organization, Oculos Development Services (a subsidiary of iuvo BioScience), which has been instrumental in the successful completion of the first two RM trials. Enrollment of these trials has been remarkably expeditious due to the straightforward trial design and the engagement of experienced optometry and ophthalmic practice sites. Together, there is a high degree of confidence to deliver top-line results in the first quarter of 2022 after just initiating in the middle of this quarter.
Edward Holland, MD, Director of Cornea at Cincinnati Eye Institute and Professor of Ophthalmology at the University of Cincinnati said, “In current practice, to achieve an optimal examination of the retina, ophthalmologists and optometrists regularly dilate patients to perform monitoring and screening for diseases of the eye. Patients often complain after dilation, citing unwanted symptoms including photophobia, loss of accommodation, inability to read clearly, inability to return to work, and subjective discomfort for hours. Other patients forgo dilation completely at annual visits, limiting our ability to perform a comprehensive exam. There are no currently approved treatments available, and it is exciting to see the steady advancement towards potential FDA approval for Nyxol. Nyxol is a drop that has demonstrated rapid reversal of dilation in dark and light irides. It can also be used to more quickly reverse the most commonly used mydriatic agents such as phenylephrine and tropicamide. Nyxol could be widely used in our clinical practices, which could increase dilated exams and promote better overall eye health in our patient population.”
Reversal of Mydriasis Market Opportunity
Every year in the U.S., an estimated 100 million eyes are dilated to examine the back of the eye either for routine check-ups, disease monitoring, or surgical procedures across all eye care practice groups. Depending on the individual and the color of their eyes, the pharmacologically-induced dilation can last anywhere from 6 to 24 hours. Dilated eyes have heightened sensitivity to light and an inability to focus on near objects, causing difficulty reading, working, and driving.
Market research conducted by GlobalData surveyed several hundred patients and eye care providers (optometrists and ophthalmologists) about Reversal of Mydriasis. More than 65% of surveyed patients reported moderate to severe negative impact of a dilated pupil. These data underscore the potential value of the role of the investigational product candidate Nyxol in improving comfort and daily function after pupil dilation. Furthermore, approximately 80% of patients responded that they would be likely to request a dilation reversal drop, and more than 70% of eye care providers would be likely to use a reversal drop. The market research confirmed the patients’ willingness to pay out-of-pocket to reverse their dilations with an attractive market size estimated at more than $500 million. Ocuphire is currently evaluating partnering options for an efficient and effective commercial launch of Nyxol targeted for the second half of 2023.