Ocuphire Pharma, Inc. and Viatris Inc. announced that the FDA has approved RYZUMVI (phentolamine ophthalmic solution) 0.75%, indicated for the treatment of pharmacologically-induced mydriasis produced by adrenergic agonists or parasympatholytic agents.
Tell me more about this drug.
Originally developed under the name Nyxol, RYZUMVI (pronounced REE-ZOOM-V) is an antimicrobial, preservative-free, topical eye drop formulation.
As a relatively non-selected alpha-1 and alpha-2 adrenergic agonist, the solution’s active ingredient, phentolamine, is key in its mechanism of action.
To note, pupil dilation is largely controlled by the radial iris dilator muscles around the pupil—which are activated by the alpha-1 adrenergic receptors.
So how does it work?
Per the companies, phentolamine works to reversibly bind the alpha-1 adrenergic receptors located on the iris dilator muscle, resulting in a reduction of the pupil diameter.
From there, it “directly antagonizes the mydriatic effect of an α-1 adrenergic agonist,” thus causing an indirect reversal of mydriasis (RM).
What’s the recommended dosage?
Per the drug’s prescribing information, two different dosages are recommended for two age groups:
- For adult and pediatric patients (age 12+)
- One to two drops are to be instilled in each dilated eye following the completion of an ophthalmic exam or RM procedure.
- For pediatric patients (ages 3 to 11)
- One drop is to be instilled in each dilated eye following completion of an ophthalmic exam or RM procedure.
See here for the complete prescribing information.
Gotcha. What’s the clinical data on it?
The approval is based on the MIRA clinical trial program, which included 600+ patients.
Then-Nyxol showed a favorable safety and tolerability profile for RM across all studies: MIRA-1 (NCT04024891)MIRA-2 (NCT04620213)MIRA-3 (NCT05134974)
It also performed favorably in the MIRA-4 phase 3 pediatric safety trial (NCT05223478).
Give me a few details.
The MIRA-2 and MIRA-3 trials both met their primary and secondary endpoints, with Nyxol exhibiting a statistically significant superiority in comparison to a placebo with dilated eyes returned to baseline pupil diameter as early as 60 to 90 minutes.
To note, the MIRA-4 trial’s positive data signaled potential for Nyxol in RM to treat pediatric patients ages 3 and older.
Any adverse events reported ?
Per the prescribing info, the most common reactions include:
- Instillation site discomfort (16%)
- Conjunctival hyperemia (12%)
- Dysgeusia (6%)
Significance?
With this approval, RYZUMVI is now the only commercially available treatment option in the United States indicated for the reversal of mydriasis.
Lastly … when will it be available?
Per the companies, the drug is expected to be commercially available in the U.S. in the first half of 2024.