Ocuphire Pharma announced that results from its ORION-1 phase 2 clinical trial evaluating the safety and efficacy of Nyxol in glaucoma and presbyopia have been published in Clinical Ophthalmology.
The paper, titled “Phentolamine Mesylate Ophthalmic Solution Provides Lasting Pupil Modulation and Improves Near Visual Acuity in Glaucoma Patients in a Randomized Phase 2b Clinical Trial,” reported the following key findings:
- Use of Nyxol eye drops produced a statistically significant 20% mean reduction or approximately 1 mm in pupil diameter under daytime and nighttime lighting conditions that was sustained for over 30 hours post-dosing;
- Over 60% of patients in the Nyxol treatment group demonstrated a statistically significant improvement of 1-line or greater in near visual acuity compared to 20% on placebo;
- There was no statistical difference in eye redness compared to placebo upon examination the following morning after dosing the prior evening before bedtime; and
- Nyxol eye drops demonstrated with daily evening dosing for 2 weeks a tolerable profile with no systemic effects and an IOP lowering trend, especially for those with IOP baselines that were slightly higher than the normal range.
Highlights from this double-masked, randomized, placebo-controlled, multiple-dose, multicenter phase 2b trial were first presented by Jay Pepose, MD, at the Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting 2020. The peer-reviewed journal publication can now be found at on Ocuphire’s website here.
“We are excited to announce the second peer-reviewed publication of clinical results from our second recent phase 2 trial in our Nyxol program and would like to thank the authors, who include the five site investigators, our medical monitor at Oculos, and our team at Ocuphire for their contributions,” Mina Sooch, MBA, President and CEO of Ocuphire Pharma, said in a company news release. “The findings of the ORION-1 trial and our comprehensive end of phase 2 meeting with the FDA in May 2020 set the direction for us to also pursue Nyxol in presbyopia. We believe that 2021 could be a transformational year for Ocuphire with 4 late-stage trials planned with our Nyxol eye drops in front of the eye indications and APX3330 oral tablets for diabetic retinal disease, starting with the first phase 3 data read-out expected at the end of first quarter 2021.”
The ORION-1 phase 2 trial together with the MIRA-1 phase 2 trial established Ocuphire’s strategy to focus on acute and chronic pupil modulation indications: night vision disturbances (NVD), reversal of mydriasis, and presbyopia. The observation from the trial of durable moderate miotic effects combined with many presbyopia patients experiencing a 1-line improvement in near visual acuity confirmed the potential overall benefits of a smaller pupil aperture for improvement in everyday vision. The results also reaffirmed the potential for Nyxol, a moderate miotic, to be combined with another moderate miotic with the goal to achieve “pinhole” diameter of 1.6 mm to 2.0 mm. This target diameter has been demonstrated by ophthalmic devices and pharmacological treatments to achieve the primary endpoint of 3-line near vision improvement in many patients.
Accordingly, Ocuphire is planning to initiate VEGA-1, a phase 2 randomized, double-masked, placebo-controlled trial investigating a combination of 1% Nyxol and low dose (0.4%) pilocarpine to treat presbyopia. Ocuphire believes that the addition of low-dose pilocarpine, a miotic that works through a different iris muscle and mechanism than Nyxol, may synergistically produce the “pinhole” effect on the pupil as well as reduce the side effects common with higher approved doses of pilocarpine.
For NVD, Ocuphire’s most advanced chronic ophthalmic indication, the same daily evening dosing regimen from ORION-1 for Nyxol is planned. Ocuphire recently initiated the LYNX-1 phase 3 randomized, double-masked, placebo-controlled trial in 160 NVD patients. The primary endpoint in this registration trial is the percentage of subjects with at least 3 lines of improvement in mesopic, low-contrast, best-corrected distance visual acuity after 7 days. Secondary endpoints include pupil diameter reductions, other visual acuity measures (distance and near), and safety and tolerability. Additional information about the LYNX-1 phase 3 trial can be found at www.clinicaltrials.gov (NCT04638660).