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Opus Genetics' VEGA-3 presbyopia trial meets endpoints for phentolamine 0.75%

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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

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.

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!

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