The MIRA-3 Phase 3 FDA Registration trial for Nyxol met its primary endpoint with 58% of treated subjects returning to baseline pupil diameter at 90 minutes compared to 6% of placebo subjects.
Ocuphire Pharma Inc. announced today positive topline results in MIRA-3 (NCT05134974), its second Phase 3 registration trial of Nyxol for the reversal of pharmacologically induced mydriasis.
Ocuphire announced positive results from its first Phase 3 trial, MIRA-2, in March 2021.
According to the company, 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-3 was designed as a multi-center, randomized, parallel arm, double-masked, placebo-controlled Phase 3 trial evaluating the safety and efficacy of Nyxol in subjects with pharmacologically-induced mydriasis.
MIRA-3 enrolled 368 subjects from November 2021 to February 2022 at 16 sites in the U.S.
These topline results demonstrated that the MIRA-3 trial met its primary endpoint with 58% of subjects (study eye) treated with Nyxol returning to ≤ 0.2 mm of their baseline pupil diameter (PD) at 90 minutes compared to only 6% of subjects (study eye) treated with placebo (p < 0.0001). The effect was also significant at 60 minutes (Nyxol 42% vs. placebo 2%, p < 0.0001). In comparison, only 36% of placebo treated subjects returned back to baseline PD at 6 hours. These results showed clinically meaningful differences between Nyxol and placebo for accelerating reversal of pharmacologically-induced mydriasis.
Mina Sooch, MBA, president and CEO of Ocuphire Pharma, noted that the completion of the MIRA-3 Phase 3 trial is a major milestone in the company’s development program for Nyxol in RM.
“We are delighted with the positive efficacy and safety outcomes which confirm the results from our prior MIRA-2 Phase 3 trial,” Sooch said in a statement. “We now have over 900 subjects studied across 10 clinical trials of which over 550 have been exposed to Nyxol.”
Sooch also pointed out that the announcement means that that Ocuphire has two FDA registration trials to support potential approval for the RM indication.
“We intend to file an NDA with the U.S. FDA in late 2022, which, if approved, would position Ocuphire for commercial launch of Nyxol in RM in the second half of 2023,” Sooch added. “We want to thank the study participants, physicians, study site personnel, and everyone who was involved in the MIRA-2 and MIRA-3 trials for their contribution in advancing this program and bringing us closer to potentially delivering an FDA-approved treatment for RM.”
MIRA-3 is a Phase 3 registration trial evaluating the product candidate Nyxol to expedite the reversal of pharmacologically induced mydriasis.
In the trial 368 study participants (336 adults and 32 adolescents at or over age 12) were randomized 2:1 to receive Nyxol (0.75% phentolamine ophthalmic solution) or vehicle control (placebo) 1 hour after receiving one of 3 mydriatic agents.
The 3 mydriatic agents used in this trial were phenylephrine 2.5% (alpha 1 agonist targeting the iris dilator muscle), tropicamide 1% (cholinergic blocker targeting 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 as well as surgical procedures.
The study population was comprised of subjects in the modified Intent to Treat population (mITT).
Jay S. Pepose, MD, PhD, Director of the Pepose Vision Institute, a professor of clinical ophthalmology at Washington University School of Medicine, and Ocuphire Medical Advisory Board member and Board member, noted that the company’s MOA makes it an ideal agent for reversal of mydriasis, as it does not have the potential safety risks of retinal tears, accommodative spasm and angle closure associated with cholinergic agents like pilocarpine.
“The MIRA-3 and MIRA-2 trials confirm the favorable safety profile and efficacy, showing rapid reversal of mydriasis following dilation with all mydriatic agents tested and in both light and dark iris colors,” Pepose said in a statement. “In addition, the pupil reduction of 1 to 1.5 mm from baseline through 24 hours is a potential read through for our other clinical indications for Nyxol including presbyopia and night vision disturbances.”
Edward Holland, MD, director of Cornea Services at Cincinnati Eye Institute and Ocuphire Medical Advisory Board member, also pointed out that pupil dilation is a necessary tool for ophthalmologists and optometrists to screen for and monitor diseases of the eye. However, patients often find dilation problematic, citing unwanted symptoms including inability to read, photophobia, loss of accommodation, and inability to work effectively.
“Many patients complain about or refuse dilation for these reasons,” he said in the statement. “There are no approved treatments currently available for reversal of mydriasis, and with the announcement today of positive results from MIRA-3, I am very pleased to see the continued progress in advancing Nyxol toward potential FDA approval. If approved, I believe that Nyxol would be widely used in clinical practice, which could increase the overall number of dilated exams as well as improve patient experience, and lead to better eye health for our patients.”
Ocuphire collaborated closely with Oculos Development Services, a Rush, New York-based clinical research organization and subsidiary of Iuvo BioScience, on the execution of the MIRA-3 trial.
According to the company, Ocuphire recently completed enrollment of 23 pediatric subjects in the MIRA-4 trial evaluating the safety and efficacy of Nyxol eye drops to reverse pharmacologically-induced mydriasis. Top line results are expected in the second quarter of 2022. If MIRA-4 meets its endpoints, the results would potentially support a broader label for Nyxol in RM to include children as young as age 3.
Ocuphire noted that it is also on track to complete the Chemistry, Manufacturing and Controls (CMC) section of the NDA as three registration batches of Nyxol have been completed and on stability. The company said in the news release that it plans to file an NDA that includes the results of MIRA-1, MIRA-2, MIRA-3, and MIRA-4 with the FDA in late 2022.
Every year in the US, an estimated 100 million eyes dilations are conducted 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 a decreased ability to focus on near objects, causing difficulty reading, working, and driving. Currently, there are no approved or available options to safely reverse mydriasis. Nyxol has the potential to be the first and only FDA-approved agent for RM.