FDA approves Ryzumvi (phentolamine ophthalmic solution 0.75%) for the treatment of pharmacologically-induced mydriasis

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The US Food and Drug Administration (FDA) has approved phentolamine ophthalmic solution 0.75% (Ryzumvi)for the reversal of pharmacologically-induced mydriasis (RM) produced by adrenergic agonist or parasympatholytic agents, or a combination thereof, which has been formulated by Ocuphire Pharma and Viatris.¹ Formerly known as Nyxol, the freshly renamed Ryzumvi 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.

In the US an estimated 100 million eye dilations take place each year for routine check-ups, disease monitoring or surgical procedures of the retina.² Side effects of pharmacologically-induced mydriasis include sensitivity to light (photophobia) and blurred vision, lasting up to 24 hours, which may make it difficult to read, work and drive.³

The approval of Ryzumvi arrives following a New Drug Application (NDA) filing in December and acceptance of the NDA by the FDA in February. The NDA was filed in accordance with the results of the MIRA clinical trial results. When the NDA was filed, Ocuphire reported that phentolamine ophthalmic solution 0.75% rapidly returns dilated eyes to baseline pupil diameter as soon as 60-90 minutes from dilation.

Rick Rodgers, MBA, interim CEO of Ocuphire discussed the approval and work between Ocuphire and Viatris in a press release.¹

“We are pleased to receive FDA approval of RYZUMVI eye drops and look forward to Viatris’ successful commercial execution,” Rodgers said. “We are grateful to the many patients and investigators who participated in our clinical trials, as well as theOcuphire andViatris teams for their commitment to patients.”

Ocuphire reported positive top-line data from the MIRA clinical trials — MIRA-1, MIRA-2, MIRA-3 and MIRA-4 — in RM, Phase 3 LYNX-1 trial in NVD and Phase 2b VEGA-1 trial for phentolamine ophthalmic solution 0.75% as single agent and as adjunctive therapy with 0.4% low dose pilocarpine in presbyopia. Ocuphire noted that phentolamine ophthalmic solution 0.75% has been studied in a total of 12 clinical trials (3 Phase 1, 5 Phase 2, 4 Phase 3) in a total of approximately 1100 patients (with over 650phentolamine-treated) and has demonstrated promising clinical data for use in the multiple ophthalmic indications mentioned above.

The MIRA-2 and MIRA-3 trials successfully met their primary and key secondary endpoints, demonstrating statistically significant superiority of phentolamine ophthalmic solution 0.75% compared to placebo to rapidly return dilated eyes to their baseline pupil diameter as early as 60 and 90 minutes. Phentolamine ophthalmic solution 0.75% consistently showed a favorable safety and tolerability profile across all trials. In addition, the positive MIRA-4 pediatric trial results support a potential broader label for the solution in RM to include subjects aged 3 and older.

Breaking down the MIRA clinical trials

In the MIRA-2 and MIRA-3 trials, a total of 553 subjects aged 12 to 80 years, who had mydriasis induced by instillation of phenylephrine or tropicamide or a combination of hydroxyamphetamine hydrobromide and tropicamide (Paremyd) were randomized. Two drops (study eye) or 1 drop (fellow eye) of Ryzumvior placebo (vehicle) were administered one hour after instillation of the mydriatic agent.

The percentage of subjects with study eyes returning to ≤0.2 mmfrom baseline pupil diameter was statistically significantly greater (p<0.01) at all time points measured from 60 minutes through 24 hours in the Ryzumvi group compared with the placebo (vehicle) group across both MIRA-2and MIRA-3 trials (see Figure 1 in the US PI). The efficacy of Ryzumvi was similar for all age ranges including pediatric subjects aged 3 to 17 years. Pediatric subjects aged 12 to 17 years (n=27) were treated in MIRA-2 and MIRA-3 and pediatric subjects, aged 3 to 11 years (n=11) were treated in MIRA-4.

“The FDA’s approval of Ryzumvi marks a significant milestone for our Eye Care Division and underscores Viatris’ commitment to advancing eye care and enhancing access for both eye care professionals and patients,” said Viatris Eye Care Division President Jeffrey Nau, PhD.

“Comprehensive dilated eye exams are vital for early detection of vision-compromising diseases. Our hope is that by addressing patient dilation barriers, we’re empowering eye care professionals to broaden exam availability, leading to enhanced eye health outcomes. We look forward to launching Ryzumvi in the first half of next year, and to continuing to advance our robust eye care pipeline which is aimed at addressing a range of vision-related disorders."

Phentolamine ophthalmic solution 0.75% (Ryzumvi) safety information:

• Uveitis: Phentolamine ophthalmic solution 0.75% (Ryzumvi) is not recommended to be used in patients with active ocular inflammation (e.g., iritis).
• Potential for eye injury or contamination: Avoid touching the vial tip to the eye — or any other surface — to avoid potential for eye injury or contamination.
• Use with contact lenses: Advise contact lens wearers to remove their lenses prior to the instillation of phentolamine ophthalmic solution 0.75% and wait 10 minutes after dosing before reinserting their contact lenses.

Adverse Reactions

Instillation site discomfort (16%), conjunctival hyperemia (12%), and dysgeusia (6%) have been the most common reported adverse reactions.

References

1. Ocuphire Pharma and Viatrisannounce FDA approval of RYZUMVI™ (phentolamine ophthalmic solution) 0.75% eye drops for the treatment of pharmacologically-inducedmydriasis produced by adrenergic agonists (e.g., phenylephrine) or parasympatholytic (e.g., tropicamide) agents. Ocuphire Pharma. Press release. Released September 27, 2023. Accessed September 27, 2023. https://www.ocuphire.com/news-media/press-releases/detail/415/ocuphire-pharma-and-viatris-announce-fda-approval-of

2. Wilson FA, Stimpson JP, Wang Y. Inconsistencies exist in national estimates of eye care services utilization in the United States. J Ophthalmol. 2015;2015:435606. doi: 10.1155/2015/435606. Epub 2015 Aug 9. PMID: 26346484; PMCID: PMC4546761

3. PARAMYD® (hydroxyamphetamine hydrobromide/ tropicamide ophthalmic solution) 1%/0.25% US prescribing information. Somerset, NJ.: Akorn, Inc.; 2001.

4. Ocuphireannounces FDA acceptance of new drug application and PDUFA date of September 28, 2023 for Nyxol® eye drops for reversal of mydriasis. Press release. Released February 13, 2023. Accessed September 27, 2023. https://www.ocuphire.com/news-media/press-releases/detail/396/ocuphire-announces-fda-acceptance-of-new-drug-application