Published data from two phase 3 clinical trials demonstrated rapid reversal of pharmacologically-induced mydriasis with favorable safety profile.
Ocuphire Pharma, Inc. announced the publication of full results from two pivotal phase 3 clinical trials (MIRA-2 and MIRA-3) that evaluated the safety and efficacy of RYZUMVI (phentolamine ophthalmic solution 0.75%) for the treatment of pharmacologically-induced mydriasis in the peer-reviewed journal Ophthalmology.
The results 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.
As previously reported by Ocuphire, in both 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 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 timepoint and at every timepoint measured up to 24 hours following administration in both trials. 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.
Fewer subjects treated with phentolamine ophthalmic solution 0.75% (8-11%) had residual dilation at 24 hours post-dilation, compared to placebo-treated subjects (28-34%) (p<0.0001). Phentolamine ophthalmic solution 0.75% exhibited 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%).
“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. “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.”
Phentolamine ophthalmic solution 0.75% 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.
Phentolamine ophthalmic solution 0.75% is currently being evaluated in presbyopia and dim (mesopic) light vision disturbances (sometimes referred to as DLD) after keratorefractive surgery. The VEGA-3 phase 3 clinical trial for presbyopia is actively enrolling, and top-line data are expected in the first half of 2025.
The LYNX-2 phase 3 trial in patients with decreased visual acuity under low light conditions following keratorefractive surgery is also actively enrolling, and top-line data are expected in the first quarter of 2025.
Read the full manuscript of the Ophthalmology publication here: Ophthalmology
MIRA-2 and MIRA-3 Pivotal Trials Design
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). The primary endpoint was the percentage of subjects returning to within 0.2 mm of baseline pupil diameter in the study eye at 90 minutes post-administration, and participants were followed for 24 hours. For more information, please refer to www.ClinicalTrials.gov (NCT04620213 and NCT05134974).
About Pharmacologically Induced Mydriasis
An estimated 100 million eye dilations are conducted every year in the U.S. to examine the retina (i.e., the back of the eye) for routine check-ups, disease monitoring or surgical procedures. Pharmacologically-induced pupil dilation (mydriasis) can last up to 24 hours in adults and children with side effects such as sensitivity to light (photophobia) and blurred vision, which may make it difficult to read, work or drive.
About Phentolamine Ophthalmic Solution 0.75%
Phentolamine ophthalmic solution 0.75%, Ocuphire’s late-stage product candidate, is a non-selective alpha-1 and alpha-2 adrenergic antagonist designed to reduce pupil size. It works by uniquely blocking the alpha-1 receptors found on the radial iris dilator muscles, which are activated by the alpha-1 adrenergic receptors, without affecting the ciliary muscle. phentolamine ophthalmic solution 0.75% is being developed for presbyopia (VEGA-3 phase 3 trial) and dim (mesopic) light vision disturbances (sometimes referred to as DLD) after keratorefractive surgery (LYNX-2 Phase 3 trial). A Phase 2 and the first phase 3 trial for the use of phentolamine ophthalmic solution 0.75% to treat presbyopia met their primary endpoints.
Ocuphire is responsible for managing the VEGA-3 and LYNX-2 trials. Under the terms of the License Agreement, Ocuphire’s partner will reimburse Ocuphire for agreed-to budgeted costs related to the development of Phentolamine Ophthalmic Solution 0.75% through FDA approval, and then share costs above an agreed upon threshold amount.