Tenpoint Therapeutics, Inc. released positive topline data from BRIO-II, a phase 3 pivotal trial evaluating the company’s preservative-free (PF) ophthalmic solution for presbyopia: BRIMOCHOL PF.
Let’s get a refresh on this company.
The global, clinical-stage biotechnology company has undergone significant changes since launching in July 2023—most recently: its December 2024 merger with Visus Therapeutics.
Uniting under the Tenpoint name, this newly-merged company is focused on developing a pipeline of ophthalmic therapeutic medicines—with a focus on “rejuvenating vision in the aging eye.”
Its pipeline targets the following indications: presbyopia, presbyopia/cataract, and geographic atrophy.
Its lead investigational candidate: BRIMOCHOL PF (originally developed by Visus).
Talk about this ophthalmic solution.
Intended for once-daily administration, BRIMOCHOL PF is a topical, preservative-free, and fixed-dose ophthalmic solution formulated with two FDA-approved pharmaceuticals:
- Carbachol
- A cholinergic agent
- Known for its potency and increased duration of activity as a miotic agent
- Its mechanism of action (MOA): Reduces pupil size, resulting in near visual acuity (VA) improvement via pupil constriction
- A cholinergic agent
- Brimonidine tartrate
- A highly-selective alpha-2 agonist
- Its MOA: Prevents ciliary muscle contraction via alpha-2 receptor activation
- The potential: Mitigation of miotic side effects
How do those individual formulations work together?
Using the MOAs from each, BRIMOCHOL PF creates and sustains a “pinhole effect” by reducing the pupil size to allow only centrally-focused light rays to enter the eye.
The intended effect: Enhanced, sustainable vision and clarity for near (such as reading or smartphone/tablet use) and intermediate visual tasks (like staring at a computer screen).
- The duration of this: Ideally, anywhere from 8 to 10 hours.
Very cool! Now onto this phase 3 trial.
Dubbed BRIO-II, the multicenter, double-masked, randomized, safety and efficacy trial (NCT05135286) is the second of two phase 3 studies evaluating BRIMOCHOL PF for presbyopia.
- The participants: 629 patients (aged 45 to 80) diagnosed with emmetropic phakic or pseudophakic presbyopia (criteria here)
- The setup: Study eyes were randomized to receive a single drop in each eye of one of the following, once daily, for 12 months:
- BRIMOCHOL PF
- Carbachol PF
- Placebo
- The primary outcome measure: 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
- Time frame: Baseline Day 1 to Month 12
And what were the reported findings?
Per Tenpoint, the study 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).”
Plus: The candidate also demonstrated “clinically and statistically significant reductions in pupil size at all time points”—a major win, as this is part of BRIMOCHOL PF’s MOA.
Exactly how significant were these reductions?
The company reported that this pupil size reduction was achieved while also improving distance vision and providing a “gradual resolution of miosis over 10 hours.”
The long-term effect: Less miosis later in the day could potentially minimize night-time vision challenges, according to Tenpoint.
Any adverse side effects?
Not over the 12-month dosing phase—BRIMOCHOL PF was reported to be “well tolerated” with no treatment-related serious adverse events (AEs).
- Even further: There was no tachyphylaxis noted in both vision and pupil effects.
What other promising effects were observed?
Upon additional analysis, the company found the formulation to significantly improve reading speed and patient-reported quality of life (QoL) outcomes (based on the National Eye Institute [NEI]-Refractive Error QoL questionnaire.
- More data on those findings are expected to be presented later this year.
Also: Tenpoint Chief Medical Officer Rhett Schiffman, MD, MS, MHSA, noted the unique benefit of brimonidine in BRIMOCHOL PF led to an:
- Increase in the magnitude and duration of action of carbachol
- Reduction in the incidence of hyperemia (eye redness) over carbachol alone
Sounds promising! And how does this data compare to the first phase 3 trial?
In BRIO-I? Pretty similar in terms of meeting its primary endpoint.
Specifically: Topline data released in May 2023 found that the study achieved (beginning at hour 1) a ≥15 Early Treatment Diabetic Retinopathy Scale (ETDRS) letter gain in binocular near visual acuity (BNVA).
- This was achieved without loss of ≥5 letters at distance across all time points through Hour 6 (carbachol p=0.006; brimonidine p=0.039).
See more on that data.
So what’s significant about this latest data?
As Dr. Schiffman stated: “BRIMOCHOL PF is the only presbyopia-correcting eyedrop to have gone through a 12-month safety study” as well as be evaluated in the largest and longest safety study ever conducted in the presbyopia eye drop category.
And what’s next for the company?
In light of this positive data, Tenpoint is planning to file for regulatory approval in the U.S. within the first half (H1) of 2025.
You know what that means … stay tuned!