Opus Genetics, Inc. announced the release of positive topline phase 3 findings from the VEGA-3 trial evaluating phentolamine ophthalmic solution (POS) 0.75% for the treatment of presbyopia.
This news comes just weeks after the company reported positive phase 3 data on POS 0.75% for another proposed indication: significant, chronic night driving impairment in keratorefractive patients with reduced mesopic vision.
Sounds like a busy month for Opus! Let’s start with this solution.
POS 0.75% is an antimicrobial, preservative-free (PF), topical eye drop solution formulated with phentolamine as its active ingredient.
- What to know about phentolamine: This is a reversible, nonselective alpha-1 and alpha-2 adrenergic agonist with antimicrobial properties.
As for POS 0.75%: Administered as an eye drop, the solution reduces pupil size (diameter) by blocking the alpha-1 receptors found on the radial iris dilator muscles (activated by the alpha-1 adrenergic receptors)—without affecting the ciliary muscle.
Talk indications.
While POS 0.75% is currently under phase 3 clinical evaluation for presbyopia and keratorefractive patients with visual disturbances under mesopic, low-contrast conditions, it was previously granted FDA approval in 2023 for another indication.
- That condition: pharmacologically-induced mydriasis produced by adrenergic agonists or parasympatholytic agents
- The product name: RYZUMVI (check out its approval details).
Now to this clinical study.
The VEGA-3 trial (NCT06542497) is the second of two phase 3 trials (the other being VEGA-2, which has concluded) evaluating POS 0.75% for presbyopia treatment to support an eventual new drug application (NDA) submission for FDA approval.
Some details on this study’s setup:
- The design: Randomized, double-masked, placebo-controlled, multicenter trial
- The participants: 545 (aged 45 to 64) diagnosed with presbyopia
- The setup: Randomized 3:2 to receive one dose of either of the following each night:
- POS 0.75%
- Placebo solution
- The duration: Eight days (with patients followed up to 48 weeks)
- The outcome measure: Percentage of participants with ≥ 15 letters of improvement in binocular DCNVA and with < 5 ETDRS letters of loss in binocular distance-corrected VA (BCDVA) from baseline, and comparing POS 0.75%-treated participants to placebo-treated participants at 12 hours post-dose at Visit 4.
- Measured at Day 8
And this topline data?
To start: The study met its primary endpoint, demonstrating a statistically significant (27.2%) number of POS 0.75%-treated participants achieving a ≥15-letter improvement in binocular DCNVA.
- A less than 5-letter loss in BCDVA was observed 12 hours post-dose on Day 8
- Compare this to 11.5% of patients treated with the placebo solution (p < 0.0001)
As an added bonus: Key secondary efficacy endpoints (unidentified by the company) were also met.
Go on …
A reported 20.6% of POS 0.75%-treated patients achieved ≥15-letter ETDRS (≥3-line) gain in DCNVA at 1-hour post-dose on Day 1
- Compare this to 6.1% of those receiving placebo (p=0.0002).
Any adverse events?
POS 0.75%’s safety profile in this study was consistent with that seen in prior clinical trials—with no reports of treatment-related serious adverse events (AEs) and no evidence of any tachyphylaxis across the 6-week period.
- Notably: The most common treatment-emergent AEs (≥5%; of which all were mainly mild) included:
- Conjunctival hyperemia
- Instillation site irritation
- Dysgeusia
What’s next for this study?
Opus shared that participants will continue to be monitored for long-term safety over a 48-week period.
- Keep in mind: The study isn’t expected to conclude until June 2026 (with primary completion by October 2025).
Noted. So what did the company have to say?
Opus’s Chief Medical Advisor Jay Pepose, MD, PhD, noted that the data provides further validation supporting POS 0.75% “as a differentiated approach to managing presbyopia, reflected by its ability to improve near vision while preserving distance vision without compromising low contrast vision.”
Important to note: Dr. Pepose served as the study chair of the trial.
Speaking of validation … how did this data compare to prior presbyopia trials?
Both the VEGA-1 (phase 2; NCT04675151) and VEGA-2 (phase 3) studies met their primary endpoints.
More specifically: Those trials also found POS 0.75%-treated patients experienced statistically significant improvements in near visual acuity.
Nice! And what’s on tap for the immediate future?
Aside from the VEGA-3 study continuing, Opus intends to use data from both phase 3 trials to support an NDA submission to the FDA by the second half (H2) of 2025.
- Check out what else to expect from the company in the coming months.
As always—stay tuned for updates!