How Tryptyr and Acoltremon Stimulate Tear Production
Tryptyr is the brand name for acoltremon, a TRPM8 thermoreceptor agonist approved as a twice-daily eye drop for signs and symptoms of adult dry eye disease.
Timeline
- May 28, 2025: The FDA approved Tryptyr for adult dry eye disease.
- Day 14 in pivotal trials: Investigators assessed the proportion of participants with a specified increase in Schirmer tear score.
The U.S. Food and Drug Administration approved Tryptyr on May 28, 2025 for the signs and symptoms of dry eye disease in adults. Tryptyr is the brand name; acoltremon is the active drug. It is a 0.003 percent ophthalmic solution supplied for use as an eye drop. [1][2]
Acoltremon is an agonist of the transient receptor potential melastatin 8, or TRPM8, thermoreceptor. An agonist activates its target receptor. FDA’s review identifies TRPM8 stimulation as the drug’s pharmacologic approach, while also stating that the exact mechanism by which Tryptyr increases tear production in dry eye disease is unknown. [1][2]
The approved regimen is one drop in each eye twice daily, approximately 12 hours apart. The single-use vial can dose both eyes and should be discarded after use. This schedule is specific to Tryptyr and should not be substituted for instructions belonging to other prescription or nonprescription dry-eye products. [1][2]
FDA evaluated efficacy using the COMET-2 and COMET-3 randomized, double-masked, vehicle-controlled Phase 3 trials. Together they included 931 participants with dry eye disease. The primary endpoint measured how many achieved at least a 10-millimeter increase from baseline in an unanesthetized Schirmer tear test on day 14. [1]
Across the pooled pivotal trials, 48.3 percent of Tryptyr participants reached that tear-production threshold, compared with 10.9 percent receiving vehicle. The Schirmer test measures wetting of a paper strip and provides an objective tear-production result. It is one measure and does not capture every symptom or experience of dry eye. [1]
The most common treatment-emergent event in FDA’s trial summary was pain at the instillation site, described as burning or stinging. It occurred in 49.7 percent of the Tryptyr group and 4.1 percent of the vehicle group. The risk review says most such events were mild and resolved quickly. [1][2]
Approval means FDA found the submitted evidence sufficient for the labeled adult use; it does not mean the drops are appropriate for every cause of eye discomfort. Infection, injury and other eye conditions can resemble dry eye. Patients should use the current prescribing instructions and seek professional evaluation for persistent, severe or changing symptoms. [1][2]