Ocuphire Pharma releases results from MIRA-2 and MIRA-3 clinical trials for phentolamine ophthalmic solution 0.75% for pharmacologically-induced mydriasis

(Image Credit: AdobeStock/New Africa)

Ocuphire Pharma Inc announced results from 2 pivotal Phase 3 clinical trials (MIRA-2 and MIRA-3) that evaluated the safety and efficacy of phentolamine ophthalmic solution 0.75% (Ryzumvi) for the treatment of pharmacologically-induced mydriasis.

Results of the clinical trials were published in the peer-reviewed journal Ophthalmology.¹

According to the company, results from the clinical trials demonstrated that phentolamine ophthalmic solution 0.75%, a non-selective alpha-1 and alpha-2 adrenergic antagonist, rapidly and effectively reversed pharmacologically-induced pupil dilation with a favorable safety profile.¹

David Wirta, MD (Image credit: David Wirta, MD)

“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,” David Wirta, MD, a principal investigator in both trials, said in a news release. “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. In addition, the acceptance of the publication in a top ophthalmology journal underscores the significance of the results and the benefit to patients.”

The solution, named Ryzumvi, received FDA approval 1 year ago. It is a preservative-free, stable eye drop, which blocks the α1 receptor within the iris dilator muscle without affecting the ciliary muscle. The result is intended to reverse pharmacologically-induced mydriasis, presbyopia, and night vision disturbances.

The company reported that in the MIRA-2 (NCT04620213) and MIRA-3 (NCT05134974) clinical trials, a statistically significant greater percentage of subjects treated with phentolamine ophthalmic solution 0.75% achieved reversal of pharmacologically-induced mydriasis at 90 minutes compared to those receiving placebo, which was the primary endpoint.

In the clinical trials, subjects received the solution or placebo administered 1 hour after mydriasis, induced by instillation of either 2.5% phenylephrine, 1% tropicamide, or Paremyd (1% hydroxyamphetamine / 0.25% tropicamide).²

In the MIRA-2 trial, 48.9% of subjects treated with phentolamine ophthalmic solution 0.75% achieved reversal versus 6.6% in the placebo group (p < 0.0001).

In the MIRA-3 trial, 58% of subjects treated with phentolamine ophthalmic solution 0.75% achieved the primary endpoint versus 6% in the placebo group (p < 0.0001). Effects were observed as early as 60 minutes following administration, with significant improvements in pupil diameter at that time point and at every time point measured up to 24 hours following administration in both trials.²

According to the company, more subjects receiving phentolamine ophthalmic solution 0.75% reported a perceived benefit in the resolution of visual symptoms caused by pharmacologically-induced mydriasis compared to placebo, with statistically significant differences noted as early as one hour following administration.¹

Moreover, fewer clinical trial participants treated with ophthalmic solution 0.75% (8% to 11%) had residual dilation at 24 hours post-dilation, compared to placebo-treated subjects (28% to 34%) (p<0.0001).

The investigators noted the solution also demonstrated a favorable safety profile, with the most common treatment-emergent adverse events being mild and transient, including conjunctival hyperemia (11.2%), instillation site discomfort (10.9%) and dysgeusia (3.6%).^1,2

The solution is approved and marketed as Ryzumvi for the treatment of pharmacologically-induced mydriasis produced by adrenergic agonists (e.g., phenylephrine) or parasympatholytic agents (e.g., tropicamide), by Ocuphire’s commercial partner.

According to study, the MIRA-2 and MIRA-3 trials were randomized, double-masked, placebo-controlled, multi-center, Phase 3 clinical trials evaluating phentolamine ophthalmic solution 0.75% in 553 healthy subjects, from 12 to 80 years old.

Subjects were randomized 1:1 (MIRA-2) and 2:1 (MIRA-3) to receive either phentolamine ophthalmic solution 0.75% or placebo eye drops following pharmacologically-induced mydriasis, induced by instillation of either 2.5% phenylephrine, 1% tropicamide or Paremyd (1% hydroxyamphetamine / 0.25% tropicamide).²

The study’s researchers noted that solution treatment had a rapid onset in reducing PD within 60- to 90-minutes, with a statistically significant time savings of 3 to 4 hours to return to baseline PD compared to placebo.

“One or 2 drops of POS rapidly reversed mydriasis in all subjects regardless of mydriatic agent or iris color,” they wrote in the study.

Reference:

1. Ocuphire Pharma. Ocuphire Pharma Announces Publication of Full Phase 3 Results of Phentolamine Ophthalmic Solution 0.75% for Pharmacologically-Induced Mydriasis in Ophthalmology. GlobeNewswire News Room. Published September 30, 2024. Accessed September 30, 2024. https://www.globenewswire.com/news-release/2024/09/30/2955118/0/en/Ocuphire-Pharma-Announces-Publication-of-Full-Phase-3-Results-of-Phentolamine-Ophthalmic-Solution-0-75-for-Pharmacologically-Induced-Mydriasis-in-Ophthalmology.html

2. Jay Prepose, et al. Reversal of Pharmacologically Induced Mydriasis with Phentolamine Ophthalmic Solution.Ophthalmology, Published September 16, 2024. Accessed September 30, 2024.