FDA approves phentolamine ophthalmic solution 0.75% (Ryzumvi) for presbyopia

The US FDA approved phentolamine ophthalmic solution 0.75% (Ryzumvi; Opus Genetics) for the treatment of presbyopia in adults, according to a company announcement.¹ The preservative-free topical solution was already approved for pharmacologically induced mydriasis. Approval rests on the phase 3 VEGA-2 and VEGA-3 trials, which met their primary and all key secondary end points.¹

The approval gives eye care providers a new pharmacologic option for adults with presbyopia. Phentolamine is a non-selective alpha-1 and alpha-2 adrenergic antagonist, and the drug reduces pupil diameter without engaging the ciliary muscle.¹ Viatris, through an affiliated entity, holds exclusive US commercialization rights under a global licensing agreement with Opus Genetics.¹

“This approval marks an important milestone for Opus Genetics, representing our second US drug approval and underscoring our clinical and regulatory capabilities,” said George Magrath, MD, Opus Genetics CEO, in the release. “It reinforces our commitment to advancing innovative ophthalmic therapies that address unmet patient needs. We are grateful to the patients, investigators and clinical sites who contributed to this achievement, and we look forward to working closely with our commercial partner to bring Ryzumvi to patients.”

The VEGA-3 phase 3 trial

VEGA-3 (NCT06542497) was a multicenter, randomized, double-masked, placebo-controlled phase 3 trial conducted at 40 US sites.^2,3 Investigators randomized 545 participants 3:2 to phentolamine ophthalmic solution 0.75% or placebo, dosed once daily in the evening.² The primary end point was the proportion of participants with a gain of 15 or more ETDRS letters (3 lines) in binocular distance-corrected near visual acuity (DCNVA), with less than a 5-letter loss in binocular best-corrected distance visual acuity, 12 hours after dosing on day 8.^2,3

In the topline analysis, 27.2% of participants in the phentolamine group met the primary end point vs 11.5% with placebo (P < .0001).² At 1 hour after the first dose on day 1, 20.6% of the phentolamine group gained 15 or more letters in DCNVA compared with 6.1% with placebo (P = .0002).² The company reported no evidence of tachyphylaxis over 6 weeks relative to the day 8 result.²

Patient-reported outcomes also favored phentolamine at days 3 and 8 and week 6, including satisfaction with near vision on waking and improvement in near vision (both P < .0001).² The sponsor described the key secondary end points as met in VEGA-2 and VEGA-3.^1,2

Safety findings and prescribing details

In the company announcement, the most common ocular adverse reactions in the presbyopia trials were conjunctival hyperemia (21%) and instillation site irritation (16%).¹ The company reported no treatment-related serious adverse events in the VEGA trials.¹ In VEGA-3, the most common treatment-emergent adverse events at 5% or higher were conjunctival hyperemia, instillation site irritation, and dysgeusia, predominantly mild, and headache occurred in 2.6%.²

Ryzumvi is not recommended in patients with active ocular inflammation, such as iritis.¹ Contact lens wearers should remove lenses before instillation and wait 10 minutes before reinserting them, and patients should avoid touching the vial tip to the eye or any surface.¹ The VEGA-3 protocol includes long-term safety monitoring over 48 weeks.²

With the mydriasis indication, the most common reactions were instillation site discomfort (16%) and conjunctival hyperemia (12%), with dysgeusia (6%) as the only nonocular reaction above 5%.¹

Eye care provider takeaways

In a statement to the Eye Care Network, Alice Epitropoulos, MD, FACS, stated that she does not see these eye drops replacing contact lenses or glasses. “I frame them as an adjunct and a lifestyle option — a way to lean on readers less for intermediate and near work during the day, to complement a monovision or multifocal contact-lens plan, or to serve someone who just dislikes progressives,” she said. “I would be more cautious in higher uncorrected hyperopes and advanced presbyopes, who will likely still need correction for fine print; in patients with meaningful dry eye or surface disease, where instillation discomfort and redness matter more.

“Rather than expecting one universally superior product, I see these drops as potentially complementary options. Phentolamine's mechanism may make it particularly attractive for patients who want a non-miotic, non-accommodative approach,” Epitropoulos continued.

For John Hovanesian, MD, although he expects the the approval to aid in the increase of patients taking presbyopia drops, he finds that these approaches to presbyopia treatment have been met tend to have a subdued interest in clinicians and patients alike.

“With regard to lifestyle drugs and their likelihood of success in the marketplace, doctors debate, but patients decide,” he told the Eye Care Network. “So far, the available drugs for presbyopia have met with limited enthusiasm both from doctors and from patients. That's because all have limited efficacy, and all have at least some side effects. Presbyopia is a tough indication for many reasons, including the fact that it's hard to compete with reading glasses. Also, presbyopia clinical trial outcomes are dependent on patient effort, room lighting, the coexistence of mild cataract, dry eye, and other factors. Clinical trial results are important because they are the bar the drug must overcome to reach the market, but clinical trial results have only a little to do with commercial success.

“On the positive side, phentolamine has been well tolerated by patients seeking reversal of mydriasis. We know this because many patients ask for it with every dilated exam. If the real world efficacy of phentolamine for presbyopia matches the indications, we will have a successful drug and an expanding pool of patients taking drops for presbyopia,” he continued.

Contact lens wearers need specific instructions on lens removal and reinsertion timing, and patients with active ocular inflammation are not recommended for treatment.¹ The announcement did not state a launch date or label dosing instructions, so practices should confirm availability and prescribing information with Viatris and the full prescribing information.¹

References

1. Opus Genetics announces FDA approval of phentolamine ophthalmic solution 0.75% for the treatment of presbyopia. News release. Opus Genetics, Inc. October 16, 2026. Accessed October 16, 2026. https://www.globenewswire.com/news-release/2026/10/16/3382714/0/en/opus-genetics-announces-fda-approval-of-phentolamine-ophthalmic-solution-0-75-for-the-treatment-of-presbyopia.html

2. Opus Genetics announces VEGA-3 phase 3 trial met its primary end point for phentolamine ophthalmic solution 0.75% for the treatment of presbyopia. News release. Opus Genetics, Inc. June 26, 2025. Accessed October 16, 2026. https://www.globenewswire.com/news-release/2025/06/26/3105692/0/en/Opus-Genetics-Announces-VEGA-3-Phase-3-Trial-Met-its-Primary-Endpoint-for-Phentolamine-Ophthalmic-Solution-0-75-for-the-Treatment-of-Presbyopia.html

3. Randomized, double-masked, placebo-controlled, multicenter study of the efficacy and safety of phentolamine ophthalmic solution (POS) 0.75% in participants with presbyopia (VEGA-3). ClinicalTrials.gov identifier: NCT06542497. Accessed October 16, 2026. https://clinicaltrials.gov/study/NCT06542497