Underneath a Special Protocol Assessment (SPA), Ocuphire Pharma, Inc. has received an agreement from the FDA to initiate the phase 3 LYNX-2 trial on phentolamine ophthalmic solution 0.75% for the treatment of dim light or night vision disturbances (DLD; NVD).
Let’s start with this solution.
Phentolamine ophthalmic solution 0.75%is a preservative-free, topical eye drop formulation. The formulation's active ingredient—phentlamine—is a relatively non-selected alpha-1 and alpha-2 adrenergic agonist.
Of note, phentolamine can also enhance antimicrobial properties of macrolide antibiotics against Gram-negative bacteria.
And its mechanism of action?
The phentolamine solution works to reversibly bind the alpha-1 adrenergic receptors located on the iris dilator muscle, resulting in a potential reduction in pupil diameter.
To note, pupil dilation is largely controlled by the radial iris dilator muscles around the pupil—which can be activated by the alpha-1 adrenergic receptors.
And its indications?
Via a partnership with Viatris, Inc. (who will fund the development of the phentolamine solution), the solution:
- Was FDA-approved separately for reversal of mydriasis (RM) under the brand name, RYZUMVI (see here for coverage)
- Is currently in development for NVD and presbyopia (used with low-dose 0.4% pilocarpine eye drops)
- VEGA-2 phase 3 clinical trial is ongoing
Gotcha. Now what exactly is an SPA?
According to the FDA, a SPA is a process where companies developing a specific investigational candidate request a meeting with the agency to come to an agreement on the design / size of certain clinical trials.
The purpose: to “determine if they adequately address scientific and regulatory requirements for a study that could support market approval.”
It’s important to note, however, that an SPA agreement doesn’t necessarily guarantee the FDA will accept the filing of a new drug application (NDA) or biologics license application (BLA), or that the respective trial results will support regulatory approval.
Gotcha. Now talk about Ocuphire’s SPA.
In this case, the FDA’s agreement paves the way for Ocuphire to begin planning for the phase 3 LYNX-2 trial, which will evaluate phentolamine ophthalmic solution for the treatment of decreased visual acuity (VA) under dim (mesopic) light conditions.
Any details on this upcoming trial?
Yes, actually…
The study will be conducted as a multi-center, randomized, double-masked, placebo-controlled trial evaluating the use of the phentolamine formulation in up to 200 participants within the United States.
And what’s being measured?
Per Ocuphire, the primary endpoint to be evaluated would be a gain of 3 lines (15 letters) or more of distance vision improvement on a low-contrast chart in dim light conditions following 15 days of dosing.
Since this is LYNX-2, does that mean there was a prior phase 3 trial?
There was! Launched in December 2020 (and concluded in May 2022), the placebo-controlled, double-masked, multiple-dose phase 3 study (NCT04638660) evaluated the use of the phentolamine solution (vs a placebo) when administered once daily at/near bedtime for 14 days.
Learn more about that study here.
Gotcha. So what’s next for this upcoming trial?
According to Ocuphire CEO George Magrath, MD, MBA, MS, the company anticipates patient enrollment to begin before the end of Q1 2024.