Ocuphire Pharma's phentolamine ophthalmic solution 0.75% (Ryzumvi) has shown significant efficacy and a favorable safety profile in reversing pharmacologically-induced mydriasis, according to results from the pivotal Phase 3 MIRA-2 and MIRA-3 clinical trials. The findings, published in Ophthalmology, validate the FDA approval of Ryzumvi for this indication and highlight its potential to improve patient care by reducing recovery time after dilated eye exams.
The MIRA-2 and MIRA-3 trials were randomized, double-masked, placebo-controlled, multi-center studies involving 553 healthy subjects aged 12 to 80. Participants were randomized to receive either phentolamine ophthalmic solution 0.75% or placebo eye drops following pharmacologically-induced mydriasis, which was induced by instillation of either 2.5% phenylephrine, 1% tropicamide, or Paremyd (1% hydroxyamphetamine / 0.25% tropicamide).
Key Findings from MIRA-2 and MIRA-3
The primary endpoint of both trials was the percentage of subjects achieving reversal of pharmacologically-induced mydriasis at 90 minutes post-administration. In the MIRA-2 trial, 48.9% of subjects treated with phentolamine ophthalmic solution 0.75% achieved reversal compared to 6.6% in the placebo group (p < 0.0001). The MIRA-3 trial showed even more pronounced results, with 58% of subjects in the treatment group achieving 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. 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).
Safety and Tolerability
The solution demonstrated a favorable safety profile, with the most common treatment-emergent adverse events being mild and transient. These included conjunctival hyperemia (11.2%), instillation site discomfort (10.9%), and dysgeusia (3.6%).
Clinical Significance
"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," said David Wirta, MD, a principal investigator in both trials. He added that the trial results 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.
Mechanism of Action
Ryzumvi is a preservative-free, stable eye drop that blocks the α1 receptor within the iris dilator muscle without affecting the ciliary muscle. This mechanism allows it to reverse pharmacologically-induced mydriasis effectively. 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).
Ongoing Research
Phentolamine Ophthalmic Solution 0.75% is also being evaluated for presbyopia (VEGA-3 Phase 3 trial) with top-line data expected in the first half of 2025, and dim (mesopic) light vision disturbances (LYNX-2 Phase 3 trial) after keratorefractive surgery with top-line data expected in the first quarter of 2025.
