Tenpoint Therapeutics Limited has received FDA acceptance for the new drug application (NDA) of BRIMOCHOL Preservative Free (PF), an investigational ophthalmic solution for the treatment of presbyopia.
The announcement follows less than 2 months after the company submitted its NDA package.
Refresh me on this candidate.
Most notably, BRIMOCHOL PF was originally the lead investigational asset for Visus Therapeutics, Inc. before its December 2024 merger with Tenpoint.
What it is: A proprietary, pupil-modulating and fixed-dose eye drop consisting of two key FDA-approved formulations that combine to create and sustain a “pinhole effect” by reducing the pupil size to allow only centrally-focused rays to enter the eye.
- The resulting effect: Sharpened vision of distant and near images—with minimal side effects, the company has noted—for vision clarity in everyday tasks, such as reading and/or digital device usage as well as staring at a computer screen.
Nice! Now, which two formulations are utilized in BRIMOCHOL PF?
Those would be:
- Brimonidine tartrate → As a highly-selective alpha-2 agonist, this prevents ciliary muscle contraction by activating the alpha-2 receptor and (potentially) mitigating miotic side effects.
- Importantly: It prolongs that aforementioned “pinhole effect” to enable a longer duration of action
- Carbachol → This cholinergic (and miotic) agent is crucial in reducing pupil size and constricting the pupil to improve near visual acuity (VA)
- To note: This size reduction and constriction also contribute to the creation of a “pinhole effect”
And what kind of dosing schedule does this eye drop follow?
The intent is for a once-daily dosing.
To note: This schedule was tested and evaluated during clinical trials leading up to the submission of BRIMOCHOL PF’s NDA package.
Tell me about those studies.
To be specific, data from two phase 3 trials were included in the drop’s NDA submission:
- BRIO-I (NCT0527086)
- BRIO-II (NCT05135286)
The findings: First, we’ll focus on our coverage of the May 2023 topline data release from BRIO-I and January 2025 topline data reporting from BRIO-II.
Go on …
In BRIO-I: After an evaluation of almost 200 emmetropic phakic and pseudophakic presbyopia patients (aged 45 to 80), BRIMOCHOL PF met the study’s primary endpoint by:
- Achieving a ≥15 Early Treatment Diabetic Retinopathy Scale (ETDRS) letter gain in binocular near VA (BNVA) without a loss of ≥5 letters at distance across all time points—starting at Hour 1 through Hour 6 (carbachol p=0.006; brimonidine p=0.039).
And among secondary endpoints: A statistically significant reduction in pupil size was observed for all time points up to 10 hours, along with an improvement in distance vision at 8 hours.
- See here for more details.
And how did this compare to BRIO-II?
With an identical setup to BRIO-I (but a larger enrollment number of 629 patients), the study’s primary endpoint was:
- Change from baseline in near visual acuity (VA), as measured by the percentage of patients with a 3-line improvement in near VA without the loss of at least 1 line in distance VA (from baseline to Month 12).
The data: BRIO-I met its prespecified primary endpoints by “demonstrating statistically significant improvements in near vision versus vehicle at all timepoints out to 8 hours (p<0.008).”
- Similar to its performance in BRIO-I, BRIMOCHOL PF also demonstrated “clinically and statistically significant reductions in pupil size at all time points” while also improving distance vision and providing a “gradual resolution of miosis over 10 hours.”
- Why this is important: Over the long-term, less miosis later in the day may potentially minimize nighttime vision challenges.
Any adverse effects between the two?
In general, BRIMOCHL PF was well-tolerated, with no treatment-related serious adverse events.
Plus: Less than 10% of participants reported headaches in BRIO-I, while the company emphasized in BRIO-II that there was no tachyphylaxis observed in either vision and pupil effects.
So, what sets this eye drop apart from other approved presbyopia drops?
With its superior clinical trial performance, this fixed-dose combo was previously noted as the first of its kind to achieve the FDA’s requirement of statistically significant “contributions-of-elements” in presbyopia.
See here for the federal agency’s complete guidance on combination products.
Alrighty, so what’s next in its regulatory journey?
Now that the FDA has accepted BRIMICHOL’S PF NDA for review, the agency will spend the next 6+ months reviewing the application and evaluating the research on the eye drops’ safety and effectiveness.
- To note: A Prescription Drug User Fee Act (PDUFA) date of Jan. 28, 2026, has been assigned.
And a word from the FDA: It announced no plans to hold an advisory committee meeting to discuss the application.