Alcon has announced US Food and Drug Administration (FDA) approval of Tryptyr (acoltremon ophthalmic solution) 0.003%, formerly known as AR-15512, for the treatment of signs and symptoms of dry eye disease (DED).3 Tryptyr is a first-in-class TRPM8 receptor agonist (neuromodulator) that stimulates corneal sensory nerves to rapidly increase natural tear production,3 the company noted in a press release.
DED is a complex, multifactorial condition driven by a deficiency in natural tears, whether due to decreased tear production or increased tear evaporation.5-7 Many commonly used DED treatment options have limitations, including slow onset, patient dissatisfaction, and poor adherence.8-14 Among surveyed dry eye patients, only 13% felt their dry eye was well managed.14*
“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 eyecare company,” said David Endicott, CEO of Alcon, in the 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.”
According to Alcon, this approval is supported by 2 phase 3 clinical trials evaluating more than 930 patients (randomized 1:1 to Tryptyr or vehicle) with a history of DED.1-2 In COMET-2 and COMET-3, up to 4 times more Tryptyr patients experienced at least a 10 mm increase in natural tear production at Day 14, compared to vehicle, 42.6% vs 8.2% of patients in COMET-2 and 53.2% vs 14.4% in COMET-3 (both p<0.0001).1-2 Consistent results were observed at all timepoints through Day 90. Tryptyr demonstrated statistically significant natural tear production as early as Day 1.1-2
Studies in animals suggest that acoltremon, the active substance in Tryptyr, is an agonist of transient receptor potential melastatin 8 (TRPM8) thermoreceptors. TRPM8 thermoreceptor stimulation has been shown to activate trigeminal nerve signaling leading to increased basal tear production. The exact mechanism of action for Tryptyr in DED is unknown, the company said.
According to Alcon, Tryptyr is available in easy-to-use, single dose vials: 1 drop per eye, 2 times a day.3 Alcon said it expects to launch Tryptyr in the United States in the third quarter of 2025 and anticipates bringing Tryptyr to other markets in the future.
References
*Based on an online survey conducted by Chronic Dry Eye from February to April 2021 among 415 responders who reported being diagnosed with chronic dry eye. 44% reported a severe level of chronic dry eye (ie, levels 3 and 4).
1. Data on File for COMET-2 Phase 3 Study. Alcon 2025.
2. Data on File for COMET-3 Phase 3 Study. Alcon 2025.
3. Tryptyr US FDA Prescribing Information. 2025.
4. 2023 Dry Eye Products Markets Report, Market Scope, 2023.
5. Craig JP, Nichols KK, Akpek EK, et al. TFOS DEWS II Definition and Classification Report. Ocul Surf. 2017;15(3):276-283. doi: 10.1016/j.jtos.2017.05.008.
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9. Semba CP, Gadek TR. Development of lifitegrast: a novel T-cell inhibitor for the treatment of dry eye disease. Clin Ophthalmol. 2016;10:1083-1094. doi: 10.2147/OPTH.S110557.
10. Restasis. Prescribing Information. Allergan; 2012. Accessed July 8, 2024. http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/050790s020lbl.pdf
11. Hovanesian JA, Nichols KK, Jackson M, et al. Real-world experience with lifitegrast ophthalmic solution (Xiidra) in the US and Canada: retrospective study of patient characteristics, treatment patterns, and clinical effectiveness in 600 patients with dry eye disease. Clin Ophthalmol. 2021;15:1041-1054. doi: 10.2147/OPTH.S296510.
12. Cook N, Mullins A, Gautam R, et al. Evaluating patient experiences in dry eye disease through social media listening research. Ophthalmol Ther. 2019;8(3):407-420. doi: 10.1007/s40123-019-0188.
13. 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.
14. Morse H, Henneberger S, Reed J, et al. 2021 in American survey findings: living with chronic dry eye. ChronicDryEye. August 10, 2021. Accessed September 23, 2024. https://chronicdryeye.net/infographic/in-america-findings.
15. The Relationship Between Dry Eye Disease and Digital Screen Use - PMC (nih.gov).
16. Improved Dry Eye Drugs for 2022 and Beyond; https://www.aao.org/eye-health/tips-prevention/new-dry-eye-treatments-ocular-surface-disease.