Bausch + Lomb Corporation is making headway in developing an investigational oral treatment for dry age-related macular degeneration (AMD) following a “constructive” meeting with the FDA.
I wasn’t aware the company was developing an oral AMD therapy …
Not to worry, we’ve got a few details—starting with its name: BL1243 (tonabersat)
What it is: an investigational oral medicine under development to target the biological processes that the company says are “believed to contribute to retinal damage” in dry AMD.
And where did it come from?
B+L acquired this once-daily oral small molecule via a 2024 option agreement with InflammX Therapeutics.
Notably, it was previously referred to as Xiflamm with several proposed retinal indications (including both dry and wet AMD).
Explain this molecule does.
Essentially, BL1243 (tonabersat) works by blocking connexin43 (Cx43) hemichannels.
- The theory: Hemichannels that open under stress release adenosine triphosphate (ATP), which switches on the NLRP3 inflammasome and keeps chronic inflammation going in the retina and kidney.
The thought: Closing the hemichannels is meant to break that loop.
- How: Reducing and preventing extracellular ATP release enables cells to return to a non-inflammatory environment and for homeostasis to be restored.
And outside of the ophthalmic space?
Tonabersat has also undergone clinical evaluation as a potential treatment for migraines, epilepsy, and neuropathic pain—though those indications have reportedly been discontinued.
Noted. So what has B+L shared about the therapy?
The company’s BL1243 program “builds on prior clinical experience” (clinical trials) evaluating the therapeutic among an estimated 2.1K patients.
Included in these: a phase 2 study conducted by the DRCR Retina Network titled Oral Tonabersat Connexin-43 Modulator for Diabetic Macular Edema with Good Vision and published in Ophthalmology Science earlier this year.
Per those results: Though the study missed its primary goal, once-daily oral tonabersat (80 mg) was well tolerated and demonstrated evidence of target engagement and pharmacological activity.
- See here for more on this.
Next up: What do we know about this FDA meeting?
A few items—starting with the fact that it addressed “the need for treatment approaches that could enable intervention earlier in the course of dry AMD.”
And regarding B+L’s program?
The federal agency was reported to be supportive (in principle, that is) of the “proposed initial study design” for a future clinical trial evaluating oral tonabersat.
That study is expected to evaluate the therapy’s safety and how it behaves in the body.
Plus: Providing no unexpected (unfavorable) findings, B+L intends to use the data to support a future phase 2 study in dry AMD patients who haven’t yet developed advanced retinal damage.
Big plans … so when do they start?
As of now, the company is planning to kick off its initial oral tonabersat trial next year.
No further details on its study design or an exact timeframe were shared.
And how does this oral therapy compare to current AMD treatments?
Current FDA-approved AMD therapies like SYFOVRE and IZERVAY only address the late stages of AMD (geographic atrophy)—BL1243 is aiming to target a different AMD patient group: those in the early stages.
Also worth noting: Those FDA-approved options are administered via intravitreal injection; BL1243’s oral form could potentially prove to be a game changer.