Tenpoint Therapeutics, Ltd. has received FDA approval for YUVEZZI (carbachol and brimonidine tartrate ophthalmic solution) 2.75%/0.1% for the treatment of adult presbyopia.
YUVEZZI? What happened to BRIMOCHOL PF?
They’re one and the same, actually.
Gotcha. So what’s the significance of this approval?
Tenpoint emphasized that YUVEZZI is now the first and only dual-agent, presbyopia-correcting eye drop.
Meaning: A “dual-agent” or “dual-action” eye drop essentially refers to a single medication that contains active ingredients targeting two different (but complementary) mechanisms of action—simulatenously.
- The intent: To offer rapid symptom relief and long-term management of a condition.
And in this case?
The dual-agent active ingredients in YUVEZZI are brimonidine tartrate and carbachol.
We’ll start with brimonidine tartrate, a highly-selective alpha-2 agonist that prevents iris dilator muscle contraction while relaxing ciliary muscle tonic contraction—leading to alpha-2 receptor activation and (potentially) mitigating miotic side effects.
- In YUVEZZI: This prolongs the drop’s “pinhole effect” to enable a longer duration of action
As for carbachol, this cholinergic (and miotic) agent has a higher affinity at the iris sphincter muscle and less activity at the ciliary muscle.
- In YUVEZZI: It’s crucial for reducing pupil size and constricting the pupil to improve near visual acuity (VA), contributing to the creation of that “pinhole effect”
Tell me more about YUVEZZI.
What it is: A proprietary, pupil-modulating and fixed-dose eye drop consisting of carbachol and brimonidine tartrate that reduces the pupil size to allow only centrally-focused rays to enter the eye.
The result: Sharpened vision of distant and near images—with minimal side effects for vision clarity in everyday tasks (reading, digital device usage, and staring at a computer screen).
What’s the recommended dosing?
Per its prescribing information (PI), one drop should be topically instilled in each eye once a day, with a single-dose vial of the formulation containing enough to supply drops to both eyes.
A couple notes:
- If wearing contact lenses, remove before drop instillation and wait 10 minutes after dosing before reinserting the lenses
- If using more than one topical ophthalmic medication, space administrations at least 5 minutes apart
How long before its effects kick in?
Miosis is reportedly achieved at 30 minutes post-drop instillation and lasts up to 10 hours following just one drop in each eye.
And what clinical data was this approval based on?
Positive findings from two phase 3 clinical studies—BRIO I (NCT0527086) and BRIO II (NCT05135286)—that enrolled 800+ patients.
The key takeaways from those studies:
In BRIO I: YUVEZZI demonstrated superiority over the individual active ingredients—which is, take note, a requirement for FDA approval of a fixed-dose combination
- See here for more insights, including a statistically significant pupil size reduction observed for all timepoints up to 10 hours (and improvements in distance vision at 8 hours) post-instillation
In BRIO II: YUVEZZI achieved all primary near-vision improvement endpoints with statistically significant three-lines or greater improvement in binocular uncorrected near visual acuity (BUNVA) over 8 hours—without the loss of one line or more in binocular uncorrected distance VA (BUDVA)
- Additionally: The drop was well-tolerated with no treatment-related serious adverse events (AEs) observed over the +72k monitored treatment days.
- Check out more coverage on the reportedly “longest safety study conducted in presbyopia to-date.”
Talk more about those observed AEs.
Based on YUVEZZI’s PI (see Section 6.1), the most common adverse reactions (occurring in >5% of patients from the BRIO trials) include:
- Eye pain upon instillation
- Visual impairment
- Eye irritation upon instillation
- Headache
Tenpoint noted that ocular hyperemia (eye redness) was not a commonly reported side effect in both clinical trials—with the rate notably lower in patients receiving YUVEZZI (2.8%) versus carbachol alone (10.7%) in BRIO II.
Next up: warnings and precautions.
Patients should keep in mind the following potential developments (see Section 5 of the PI) when using YUVEZZI:
- Blurred vision (as miotics can cause accommodative spasm)
- Temporary dim or dark vision; caution is advised with night driving
- Retinal tear and detachment risk (rare but possible)
- Iritis
- Potential for
- Vascular insufficiency
- Eye injury or contamination
Any contraindications to be aware of?
The drop is contraindicated in patients with known hypersensitivity to its active ingredients—brimonidine tartrate and carbachol—or any of the excipients, according to the PI.
- As for drug interactions: See Section 7 of the PI for that list.
See here for more safety information.
Alrighty, now to the big question: When will this be commercially available?
Translation: Sometime between April 1 and June 30 of this year.
- See here for details on the $235 million in Series B financing Tenpoint raised to accelerate the commercialization process.