Ocuphire Announces MIRA-2 Phase 3 Registration Trial for the Reversal of Mydriasis Meets Primary Endpoint

Ocuphire Pharma announced positive topline results in the MIRA-2 phase 3 registration trial investigating its product candidate Nyxol for reversal of pharmacologically induced mydriasis (dilation of pupil for eye exams). Nyxol is a proprietary, preservative-free, stable, investigational eye drop formulation of phentolamine mesylate designed to reduce pupil size by inhibiting contraction of the iris dilator muscle. MIRA-2 was designed as a multicenter, randomized, double-masked, placebo-controlled, parallel, 24-hour phase 3 trial that planned 168 healthy study participants, and ultimately enrolled 185 study participants.

These topline results indicate that the MIRA-2 trial met its primary endpoint with 49% percent of subjects (study eye) treated with Nyxol returning to ≤ 0.2 mm of their baseline pupil diameter at 90 minutes compared to 7% of subjects (study eye) treated with placebo (P<0.0001). The study population was comprised of subjects who had received one of three mydriatic (dilating) agents in the modified Intent to Treat population (mITT). The three mydriatic agents used in this trial were phenylephrine 2.5% (alpha 1 agonist works on the iris dilator muscle), tropicamide 1% (cholinergic blocker works on the iris sphincter muscle), and Paremyd (a combination of hydroxyamphetamine hydrobromide 1% and tropicamide 0.25%), which are all commonly used in optometry and ophthalmology offices to dilate patients’ pupils for annual or special exams.

“The successful outcome of this phase 3 MIRA-2 FDA registration trial is a major milestone for Ocuphire and we are thrilled to announce these positive and clinically meaningful results. Nyxol showed a statistically significant improvement on the primary as well as multiple secondary endpoints, demonstrating its ability to more rapidly return pupil diameter back to normal baselines over multiple timepoints, breadth of iris colors, and dilating agents that work on one or both iris muscles that control pupil size,” Mina Sooch, MBA, President and CEO of Ocuphire Pharma, said in a company news release. “These phase 3 results build on a growing body of evidence to establish Nyxol’s therapeutic product profile including the positive results seen in our recently published MIRA-1 phase 2b trial. This further validates the mechanism of action, therapeutic effect, and safety profile of the Nyxol platform for potential additional refractive indications – presbyopia and night vision disturbance. We are very grateful to the study participants and investigators who participated in this U.S. study.”

Highlights of MIRA-2 Topline Efficacy and Safety Results

MIRA-2 (NCT04620213) is a phase 3 registration trial evaluating the product candidate Nyxol to expedite the reversal of pharmacologically induced mydriasis. In the trial 185 study participants (171 adults and 14 adolescents at or over age 12) were randomized 1:1 to receive Nyxol (0.75% phentolamine ophthalmic solution) or vehicle control (placebo) 1 hour after receiving one of 3 mydriatic agents.

• The primary endpoint was met with 49% percent of subjects (study eye) treated with Nyxol returning to ≤ 0.2 mm of their baseline pupil diameter at 90 minutes compared to 7% of placebo treated subjects (P<0.0001) across three mydriatic agents (phenylephrine, tropicamide, and Paremyd).
  • Multiple secondary efficacy endpoints also met statistical significance.
  • A clinically meaningful higher number of Nyxol treated subjects (study eye and non-study eye) returned to baseline pupil diameter at 60 minutes compared to placebo, and every subsequent timepoint through 6 hours post-dosing.
  • Nyxol treated subjects had mean pupil diameters that were 1 to 2.5 mm smaller than placebo treated subjects at all timepoints from 1 to 6 hours post-dosing.
  • Nyxol treated subjects returned to baseline pupil diameter more quickly than placebo treated subjects with:
  (i) all three dilating agents;
  (ii) both light and dark irides; and
  (iii) with one and two drops of Nyxol.

• Nyxol demonstrated a favorable safety profile.
  • Nyxol was well-tolerated in the study population with no serious adverse events or withdrawals due to adverse events.
  • A mild transient increase in conjunctival hyperemia was observed in Nyxol treated subjects which peaked at one hour post-dose and decreased steadily thereafter.

Jay S. Pepose, MD, PhD, Director of the Pepose Vision Institute, Professor of Clinical Ophthalmology at the Washington University School of Medicine, and Ocuphire Medical Advisory Board member commented, “I am excited to see robust effects of Nyxol in reversing pharmacologically induced mydriasis with a favorable safety profile. The phase 3 trial results exceeded my expectations with statistical and clinical significance on the primary endpoint at 90 minutes, as well as at the earlier 60 minute timepoint. In addition, Nyxol demonstrated significant benefit through 6 hours across the range of commonly used mydriatic agents, light and dark iris colors, and age cohorts. Nyxol is unique as the only alpha-1/2 antagonist in clinical trials. Nyxol has the potential to address an unmet medical need as there are no commercial treatments currently available for reversal of mydriasis. If approved for marketing by the FDA, Nyxol may provide substantial benefit to patients after dilation, and may even increase the compliance with standard of care guidance for dilated examinations during visits to eye care specialists and thereby improve overall eye health.”

Building on the positive results of this first completed phase 3 registration trial for Nyxol (MIRA-2), a second phase 3 registration trial (MIRA-3) is planned to initiate in the second half of this year. A new drug application (NDA) to obtain approval to market Nyxol for this pharmacologically induced mydriasis indication is expected to be submitted to the FDA in early 2023.

Full results from the MIRA-2 phase 3 trial will be presented at an upcoming industry conference – 2021 ASCRS Annual Meeting July 23–27 in Las Vegas, Nevada. Ocuphire also plans to submit these phase 3 results to a peer-reviewed journal for publication later this year.