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Spotlight on TRYPTYR®

Optometry 360

This Spotlight Series article is editorially independent content.

Dry eye disease (DED) is a complex, multifactorial condition characterized by decreased tear production or increased tear evaporation, resulting in a wide range of symptoms. It is one of the most common ocular surface disorders, affecting an estimated 38 million adults in the United States. Many commonly used DED treatment options have limitations, including slow onset of action, patient dissatisfaction, and poor adherence.1 Among surveyed patients with DED, only 13% reported that their condition was well managed.2

TRYPTYR®: First Neuromodulator Eye Drop

TRYPTYR (acoltremon ophthalmic solution; Alcon) 0.003% received US Food and Drug Administration (FDA) approval in May 2025 for the treatment of the signs and symptoms of DED. It is a first-in-class transient receptor potential melastatin 8 (TRPM8) receptor agonist. TRYPTYR stimulates corneal sensory nerves to rapidly increase natural tear production.1,3

Studies in animals suggest that acoltremon, the active substance in TRYPTYR, acts as an agonist of TRPM8 thermoreceptors. Activation of these thermoreceptors has been shown to stimulate trigeminal nerve signaling, leading to increased basal tear production. The exact mechanism of action for TRYPTYR in DED is unknown.3

Efficacy Data

The FDA approval was based on results from 2 phase 3 clinical trials (COMET-2 and COMET-3) that enrolled more than 930 patients with a history of DED.

COMET-2 and COMMET-3 were identical randomized, multicenter, double-masked, vehicle-controlled, phase 3 studies designed to evaluate the efficacy and safety of TRYPTYR in patients with DED. Patients were randomized to receive TRYPTYR or vehicle and administered 1 drop twice daily for 90 days. The primary endpoint was the proportion of patients who achieved a ≥10-mm increase from baseline in unanesthetized Schirmer score at day 14. The key secondary endpoint was change from baseline in global Symptom Assessment in Dry Eye (SANDE) score at day 28. Additional secondary outcomes included the proportion of patients achieving a ≥10-mm increase from baseline in unanesthetized Schirmer score at day 1 and 90, as well as changes from baseline in unanesthetized Schirmer score at day 1, 14, and 90.4

The primary endpoint was met in both studies, with up to 4 times more patients in the TRYPTYR group achieving a ≥10-mm increase in natural tear production at day 14 versus vehicle (see FIGURE 1). Statistically significant natural tear production was observed as early as day 1.4

Reductions in global SANDE score were observed with TRYPTYR as early day 7, with notable reductions by day 28. This improvement was statistically significant in COMET-2 (see FIGURE 2). Consistent results were observed at all time points through day 90, as shown in FIGURE 3.4

Safety and Tolerability

TRYPTYR demonstrated a favorable safety profile across multiple clinical trials. Among 766 patients treated with TRYPTYR across 4 clinical trials, no serious adverse reactions were reported. The most common ocular adverse reaction was instillation-site pain, reported in 50% of patients. Fewer than 1% of patients discontinued treatment because of ocular burning or stinging. In a 12-month long-term safety study, an average of 86% of patients who experienced pain reported that the sensation lasted for 1 minute or less.3,5

Dosing and Administration

The recommended dosage is 1 drop in each eye twice daily, approximately 12 hours apart. TRYPTYR may be used concomitantly with other topical ophthalmic eye drops. If more than 1 topical ophthalmic drug is used, administer them at least 5 minutes apart. If a dose is missed, patients should resume treatment with the next scheduled dose. Contact lenses should be removed prior to instilling TRYPTYR and may be reinserted 15 minutes after administration.3

For more information, visit https://tryptyr.myalcon.com/professional.

References

  1. Alcon announces FDA approval of TRYPTYR (acoltremon ophthalmic solution) 0.003% for the treatment of the signs and symptoms of dry eye disease. News release. Alcon. May 28, 2025. Accessed January 25, 2026. https://investor.alcon.com/news-and-events/press-releases/news-details/2025/Alcon-Announces-FDA-Approval-of-TRYPTYR-acoltremon-ophthalmic-solution-0-003-for-the-Treatment-of-the-Signs-and-Symptoms-of-Dry-Eye-Disease/default.aspx
  2. 2021 in American survey findings: living with chronic dry eye. net. Updated August 10, 2021. Accessed January 25, 2026. https://chronicdryeye.net/infographic/in-america-findings
  3. Package insert. Alcon Inc; 2025.
  4. Pattar GR, Wirta D, Jerkins G, et al; COMET-2 and COMET-3 Study Groups. Acoltremon ophthalmic solution 0.003% for signs and symptoms of dry eye disease: results of phase 3 pivotal COMET-2 and COMET-3 studies. 2025:S0161-6420(25)00605-0 doi:10.1016/j.ophtha.2025.09.018
  5. Data on File. Alcon, Inc.

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