FDA approves Alcon’s Tryptyr (AR-15512) for signs and symptoms of dry eye disease

In the COMET-2 and COMET-3 trials, 4 times more patients treated with Tryptyr experienced at least a 10mm increase in natural tear production at day 14 when compared to vehicle.

Alcon announced that the FDA has approved acoltremon ophthalmic solution 0.003%, a first-in-class transient receptor potential melastatin 8 (TRPM8) receptor agonist, for the treatment of the signs and symptoms of dry eye disease (DED). The drop, previously known as AR-15512, will be sold under the name Tryptyr. The neuromodulator stimulates corneal sensory nerves to increase natural tear production rapidly following instillation.¹

“Today marks a tremendous milestone for Alcon as Tryptyr becomes our first prescription pharmaceutical treatment to be approved by the FDA since becoming an independent, publicly traded eye care company,” David Endicott, CEO of Alcon, said in a press release. “We look forward to making this new treatment available to millions of patients affected by dry eye disease. We believe Tryptyr is an exciting new treatment option for a significant number of dry eye patients given its rapid efficacy.”

Many patients find DED frustrating due to its multifactorial nature. Tear deficiency may be caused by either decreased tear production or increased tear evaporation; Alcon targeted the former with Tryptyr following a survey of patients with dry eye, which found that only 13% of respondents felt their dry eye was well managed.²

“Acoltremon adds another dimension to our dry eye armamentarium,” Cory Lappin, OD, of Phoenix Eye Care, said exclusively to Optometry Times. “We have some great treatments that stabilize the tear film, reduce inflammation, and target the neural pathway, but acoltremon is the first topical drop that increases tear production using the basal tear pathway through direct stimulation of the corneal nerves via the TRPM8 receptor, which adds a novel mechanism to the fold.”

COMET clinical trial results support approval

The approval is supported by 2 phase 3 clinical trials, COMET-2 and COMET-3, that evaluated more than 930 patients with a history of DED.³ In the trials, 4 times more Tryptyr patients experienced at least a 10-mm increase in natural tear production at day 14 when compared to vehicle. COMET-2 saw 42.6% vs 8.2% of patients with at least a 10-mm increase, and COMET-3 saw 53.2% vs 14.4% (both P < .0001). Additionally, it was noted that Tryptyr demonstrated a statistically significant natural tear production as early as day 1. Acoltremon was well tolerated in the studies, and no serious ocular adverse events were reported.

Additional studies in animals suggest that acoltremon acts as an agonist of TRPM8 thermoreceptors, stimulating the trigeminal nerve to increase basal tear production. However, Alcon reports that the exact mechanism of action for Tryptyr in DED is unknown.¹

This formulation of acoltremon 0.003% was originally created and trialed by Aerie, which was acquired by Alcon in 2022.⁴

Acoltremon 0.003% will be packaged in single-dose vials, and 1 drop per eye should be administered twice a day. Alcon expects a US launch of Tryptyr in Q3 of 2025 and plans to expand to additional global markets in the future.

Reference

1. Alcon announces FDA approval of Tryptyr (acoltremon ophthalmic solution) 0.003% for the treatment of the signs and symptoms of dry eye disease. Alcon. Published May 29, 2025. Accessed May 29, 2025. https://www.alcon.com/media-release/alcon-announces-fda-approval-tryptyr-acoltremon-ophthalmic-solution-0003-treatment/

2. Mbagwu M, LaPrise A, Harris J, Nair AA, Fain J, Harrison DJ. Characterization of discontinuation and switching patterns of dry eye disease medications using linked EHR registry and claims data. Presented at: American Society for Cataract and Refractive Surgery Conference; April 5-6, 2024; Boston, MA.

3. Maharjan, EK. Alcon reports positive results from phase 3 Comet trials of AR-15512 for dry eye. Published January 10, 2024. Accessed May 29, 2025. https://www.optometrytimes.com/view/positive-results-reported-from-phase-3-comet-trials-of-alcon-s-ar-15512-for-dry-eye

4. Alcon completes acquisition of Aerie Pharmaceuticals. Optometry Times. Published November 30, 2022. Accessed May 29, 2025. https://www.optometrytimes.com/view/alcon-completes-acquisition-of-aerie-pharmaceuticals