FDA Approval and Clinical Integration of Tryptyr for Dry Eye Disease

The FDA approved Tryptyr, a first-in-class TRPM8 receptor agonist that increases natural tear production and expands topical options for dry eye disease.

The product is approved as an ophthalmic solution for topical use, supplied in single‑dose vials and recommended at one drop in each eye twice daily—an approval that immediately expands practical treatment options for patients with dry eye disease.

Tryptyr activates TRPM8 on corneal sensory nerves to stimulate physiologic tear secretion and improve ocular surface stability. This mechanism differs from lubricants that replace tear volume and from anti‑inflammatory agents that reduce surface inflammation because it promotes endogenous tear production rather than merely substituting for tears or primarily suppressing inflammation, a distinction that may yield more durable symptom control.

Approval was supported by two pivotal phase 3 trials, COMET‑2 and COMET‑3, randomized, placebo‑controlled studies enrolling approximately 930 patients randomized 1:1 to Tryptyr or vehicle. Primary endpoints included objective measures of natural tear production and validated symptom scores. Tryptyr produced rapid increases in tear production (statistically significant as early as day 1) with clinically meaningful symptom improvement by day 14: COMET‑2 reported a ≥10‑mm increase at day 14 in 42.6% versus 8.2% for vehicle and COMET‑3 reported 53.2% versus 14.4%, with benefits sustained through day 90. The most common adverse reaction was instillation‑site pain; overall tolerability was acceptable across both trials and the combined efficacy and safety profile supported approval.

Patients most likely to benefit include those with aqueous‑deficient or mixed dry eye who have persistent symptoms despite lubricants. Practical considerations include twice‑daily topical dosing with single‑use vials and routine monitoring of efficacy and local tolerability.

Looking ahead, clinicians should track accumulating postapproval real‑world experience, longer‑term tolerability, and comparative‑effectiveness data to refine Tryptyr’s place in dry eye management.

Key Takeaways:

• Tryptyr is the first‑in‑class TRPM8 agonist approved to increase natural tear production, adding a novel mechanism to dry eye therapy.
• Patients with symptomatic dry eye not controlled by lubricants in outpatient ophthalmology and optometry settings are the primary population likely to benefit.
• Tryptyr provides an additional topical option for physiologic tear stimulation that can be integrated into stepwise treatment plans while clinicians monitor for local adverse effects.