Phentolamine Ophthalmic Solution 0.75% Achieves Rapid Reversal of Mydriasis

David Wirta, MD

Credit: Eye Research Foundation

Full Phase 3 results from the pivotal MIRA-2 and MIRA-3 trials demonstrate the favorable safety and efficacy of phentolamine ophthalmic solution 0.75% (RYZUMVI™) for pharmacologically induced mydriasis.¹

Announced by Ocuphire Pharma on September 30, 2024, phentolamine ophthalmic solution 0.75% achieved rapid and effective reversal of pharmacologically-induced pupil dilation within 60 to 90 minutes, with a statistically significant time savings of 3 to 4 hours to return to baseline pupil diameter, compared with placebo.²

“Ocuphire should be proud of the results from these two pivotal trials, which formed the basis of the FDA’s approval of phentolamine ophthalmic solution 0.75% for mydriasis and further validates the scientific rationale of this agent,” said David Wirta, MD, medical director, Eye Research Foundation and a principal trial investigator.² “In addition, the acceptance of the publication in a top ophthalmology journal underscores the significance of the results and the benefit to patients.”

Pharmacologically-induced mydriasis can last up to 24 hours in adults and children with side effects, including photophobia and blurry vision, which can impact daily quality of life. In September 2023, the US Food and Drug Administration (FDA) approved phentolamine ophthalmic Solution 0.75% for mydriasis, based on results from the MIRA clinical trial program.³

MIRA-2 and MIRA-3 were randomized, double-masked, placebo-controlled, multi-center, Phase 3 trials assessing phentolamine ophthalmic solution 0.75% in 553 healthy subjects.¹ Participants aged 12 to 80 years were randomized 1:1 (MIRA-2) and 2:1 (MIRA-3) to phentolamine ophthalmic solution 0.75% or placebo following pharmacologically induced mydriasis.

The primary trial endpoints were the percentage of participants returning to ≤0.2 mm of baseline pupil diameter in the study eye at 90 minutes post-administration, with 24-hour follow-up. Safety measures involved the occurrence of treatment-emergent adverse events (TEAEs) and tolerability measures.

Achieving the primary endpoint, both trials revealed a statistically significantly greater percentage of participants treated with phentolamine ophthalmic solution 0.75% demonstrated reversal of pharmacologically-induced mydriasis at 90 minutes compared with placebo.

In MIRA-2, 48.9% of participants treated with phentolamine ophthalmic solution 0.75% achieved mydriasis reversal compared with 6.6% in the placebo group (P <.0001). In MIRA-3, 58% of participants treated with phentolamine ophthalmic solution 0.75% achieved the primary endpoint versus 6% in the placebo group (P <.0001).

Mydriasis reversal was identified as early as 60 minutes after administration of phentolamine ophthalmic solution 0.75% in both trials (24.5% vs 5.5% for MIRA-2; P <0.0003 and 42% vs. 2% for MIRA-3; p<0.0001). Fewer participants treated with phentolamine ophthalmic solution 0.75% (8–11%) experienced residual dilation at 24 hours post-dilation, compared with placebo-treated participants (28–34%) (P <.0001).

Safety results showed a favorable profile, with the most common TEAEs linked to phentolamine ophthalmic solution 0.75% being mild and transient, including conjunctival hyperemia (11.2%), instillation site discomfort (10.9%) and dysgeusia (3.6%). Participants receiving phentolamine ophthalmic solution 0.75% reported a perceived benefit in the resolution of mydriasis-related symptoms compared with placebo, noting statistically significant differences as early as one hour after administration, according to Ocuphire.²

“Routine dilated eye exams are essential for early disease detection, and offering patients faster recovery from mydriasis with minimal side effects enhances the quality of their care,” Wirta added.²

References

1. _{Pepose JS, Wirta D, Evans D, et al. Reversal of Pharmacologically Induced Mydriasis with Phentolamine Ophthalmic Solution. Ophthalmology. Published online September 16, 2024. doi:10.1016/j.ophtha.2024.09.010}
2. _{Ocuphire Pharma announces publication of full phase 3 results of phentolamine ophthalmic solution 0.75% for pharmacologically-induced mydriasis in ophthalmology. Ocuphire Pharma, Inc. September 30, 2024. Accessed September 30, 2024. https://www.ocuphire.com/news-media/press-releases/detail/443/ocuphire-pharma-announces-publication-of-full-phase-3.}
3. _{Iapoce C. FDA approves phentolamine ophthalmic solution for pharmacologically-induced mydriasis. HCP Live. September 27, 2023. Accessed September 30, 2024. https://www.hcplive.com/view/fda-approves-phentolamine-ophthalmic-solution-pharmacologically-induced-mydriasis.}