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Tryptyr COMET-2 and COMET-3 Trials Explained

FDA approved Tryptyr (acoltremon 0.003%) for signs and symptoms of adult dry eye disease after two phase 3 trials found that substantially more treated participants achieved at least a 10 mm increase in tear production at day 14 than participants receiving vehicle drops.

Timeline

  1. COMET-2 and COMET-3: Two randomized, double-masked, vehicle-controlled phase 3 studies enrolled 931 participants in total.
  2. Day 14: The primary endpoint measured the share achieving at least a 10 mm increase in unanesthetized Schirmer tear production.
  3. 2025-05-28: FDA approved Tryptyr for treatment of signs and symptoms of dry eye disease in adults.

Tryptyr is the brand name for acoltremon ophthalmic solution 0.003%, an eye drop the FDA approved on May 28, 2025, for treatment of the signs and symptoms of dry eye disease in adults. It activates TRPM8 thermoreceptors, but FDA’s review states that the exact mechanism by which it increases tear production in dry eye disease remains unknown. [1][2][3]

The principal efficacy evidence came from COMET-2 and COMET-3, two phase 3, multicenter, randomized, double-masked, vehicle-controlled studies. Together they enrolled 931 adults at 46 U.S. sites. Participants had a history of artificial-tear use and were qualified using dry-eye signs and symptoms after a vehicle run-in period. [1][3]

The primary endpoint was not a general declaration that dry eye had disappeared. Investigators measured the proportion of participants whose study eye showed at least a 10 millimeter increase from baseline in the unanesthetized Schirmer test at day 14. That test uses a paper strip to estimate tear production, making the primary result a specific objective sign. [1][3]

In COMET-2, 42.6% of Tryptyr participants met the tear-production endpoint compared with 8.2% receiving vehicle, a difference of 34.4 percentage points. In COMET-3, the corresponding figures were 53.2% and 14.4%, a difference of 38.8 points. FDA reported both differences as statistically significant, with confidence intervals that excluded zero. [1]

The two groups received either active drops or the formulation without active drug, and masking reduced expectation bias. Even so, the trials were limited to the enrolled population, protocol, follow-up and selected endpoint. The FDA snapshot also cautions that subgroup findings, including apparent racial differences, can be difficult to interpret because some groups were relatively small. [1]

Safety information came from the phase 3 trials and additional COMET studies. The current label says instillation-site pain occurred in about half of treated participants; fewer than 1% discontinued because of burning or stinging. Trial percentages cannot predict an individual reaction, and new eye pain, vision changes or signs of injury require professional assessment. [2][3]

The FDA-approved regimen is one drop in each eye twice daily, approximately 12 hours apart, but this evidence guide is not a personal treatment instruction. The label includes handling steps for the single-use vial and contact lenses, and pediatric safety and effectiveness have not been established. Adults considering treatment should use the current prescribing information and discuss other eye conditions and medicines with an eye-care professional. [1][2]

Sources

  1. FDA — Drug Trials Snapshot: Tryptyr
  2. FDA — Tryptyr prescribing information
  3. FDA — Integrated review for Tryptyr NDA 217370

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