Alcon announced the FDA has approved TRYPTYR (acoltremon ophthalmic solution) 0.003%— previously known as AR-15512—for the treatment of the signs and symptoms of dry eye disease (DED).
The approval comes just two days ahead of the previously set Prescription Drug User Fee Act (PDUFA) date of May 30.
And of major significance: This marks the first prescription-based pharmaceutical for Alcon.
Let’s just dive right in: Tell me about TRYPTYR.
We’ll start with some background: The newly-renamed TRYPTYR (pronounced Trip-Tear) was originally developed by Aerie Pharmaceuticals (acquired by Alcon in 2022).
What it is: A topical transient receptor potential melastatin 8 agonist (TRPM8 for short) formulated for topical ocular instillation.
- To note: TRPM8 is a cold-sensing receptor in the cornea and eyelid that—when stimulated—has been shown to activate trigeminal nerve signaling, leading to increased basal tear production.
- However: Alcon also noted that the “exact mechanism of action for TRYPTYR in DED is unknown.”
Interesting. So what’s the recommended dosage?
One drop of the prescription-based pharmaceutical should be instilled in each eye twice daily (BID; approximately 12 hours apart).
Importantly: TRYPTYR is packaged in single-dose vials that should be used immediately after opening (for both eyes) and then discarded.
- See here for its full prescribing information (PI).
Can it be used with contact lenses in and other eye drops?
- Contact lenses should be removed before instilling TRYPTYR into the eyes and only reinserted 15 minutes after drop instillation.
- The formulation can be used concomitantly with other topical ophthalmic drops; however, if more than one additional topical drug is being used, they should be administered at a minimum 5 minutes apart.
Gotcha. So what clinical data supported this approval?
That would be findings from two multicenter, vehicle-controlled, double-masked, randomized phase 3 clinical trials evaluating 930+ patients with a history of DED:
- COMET-2 (NCT05285644)
- COMET-3 (NCT05360966)
The setup for those trials: Patients were randomized 1:1 to receive either TRYPTYR or a vehicle BID for 90 days.
And the primary outcome measure: Unanesthetized Schirmer test (at Day 14), as measured by the number of participants with ≥ 10 mm increase in unanesthetized Schirmer score.
And what did the data show?
The initial topline data: Both studies met their primary endpoints while also demonstrating a “rapid onset and sustained tear production” in association with TRYPTYR use versus vehicle.
- This was observed as early as Day 14 and continued through to Day 90.
Specifically: Up to four times more TRYPTYR patients experienced at least a 10 mm increase in natural tear production at Day 14, compared to vehicle.
- COMET-2: 42.6% versus 8.2% of patients (p<0.0001)
- COMET-3: 53.2% versus 14.4% of patients (p<0.0001)
See here for our coverage on this original reporting.
Hold up, didn’t Alcon just release new data from these trials?
Yes, it did. In fact, new long-term clinical findings were presented at the 2025 annual meeting of the American Society for Cataract and Refractive Surgeons (ASCRS) in April.
That data was regarding another phase 3 trial in the four-study COMET clinical program (COMET-4; NCT05493111)—which, notably, was not included in Alcon’s submission for FDA approval.
The crux of those findings: Tear production was consistently observed among TRYPTYR-treated patients through the 12-month period.
- See here for further details.
Sounds promising … but were there any adverse effects across these trials?
The most common reported ocular adverse reaction—occuring in 50% of all patients—was instillation site pain.
And less than 1% of patients discontinued drop usage due to burning or stinging sensation in their eyes.
Now to the big picture: What’s significant about this approval?
As Alcon CEO David Endicott shared, TRYPTYR is the company’s first prescription-based pharmaceutical treatment to be approved since becoming an independent, publicly-traded eyecare company.
- “We believe TRYPTYR is an exciting new treatment option for a significant number of dry eye patients given its rapid efficacy,” he stated.
And on the clinical side: In Alcon’s approval announcement, ocular surface disorder expert Marjan Farid, MD, professor of Ophthalmology at the University of California, Irvine, noted that “TRYPTYR is the first eye drop that stimulates corneal nerves to directly address tear deficiency, a known cause of (DED).”
And for the company's dry eye portfolio?
We’d be remiss if we didn’t note that this approval follows Alcon’s launch of another dry eye drop just a few months ago: the over-the-counter Systane PRO Preservative-Free (PF) drops, marketed as “the longest lasting eye drop” in the company’s SYSTANE portfolio.
- Get all those details here.
Alrighty, last question: When will TRYPTYR be available for commercial use?
Alcon is planning for a Q3 2025 launch in the U.S.
So stay tuned!