Alcon Announces FDA Approval of TRYPTYR (acoltremon ophthalmic solution) 0.003% for the Treatment of the Signs and Symptoms of Dry Eye Disease

[Gretchyn Bailey]

GENEVA, May 28, 2025 – Alcon (SIX/NYSE: ALC), the global leader in eye care dedicated to helping people see brilliantly, today announced the U.S. Food and Drug Administration (FDA) has approved 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

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 eye care company,” said David Endicott, CEO of Alcon. “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.”

This approval is supported by two 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 four times more TRYPTYR patients experienced at least a 10mm increase in natural tear production at Day 14, compared to vehicle, 42.6% versus 8.2% of patients in COMET-2 and 53.2% versus 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

“Many of my patients continue to face frustrating challenges with dry eye management, and there is a clear need for additional treatment options,” said Marjan Farid, MD, Professor of Ophthalmology at the University of California, Irvine. “TRYPTYR is the first eye drop that stimulates corneal nerves to directly address tear deficiency, a known cause of Dry Eye Disease.”

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.

TRYPTYR is available in easy-to-use, single dose vials: one drop per eye, two times a day.3 Alcon expects to launch TRYPTYR in the U.S. 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 (i.e., levels 3 and 4).

• Data on File for COMET-2 Phase 3 Study. Alcon 2025.
• Data on File for COMET-3 Phase 3 Study. Alcon 2025.
• TRYPTYR® US FDA Prescribing Information. 2025.
• 2023 Dry Eye Products Markets Report, Market Scope, 2023.
• 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.
• Nattinen J, Aapola U, Nukareddy P, Uusitalo H. Looking deeper into ocular surface health: an introduction to clinical tear proteomics analysis. Acta Ophthalmol. 2022;100:486-498. doi: 10.1111/aos.15059.
• Bron AJ, de Paiva CS, Chauhan SK, et al. TFOS DEWS II pathophysiology report. Ocul Surf. 2017;15:438-510. doi: 10.1016/j.jtos.2017.05.011.
• Wilson SE, Perry HD. Long-term resolution of chronic dry eye symptoms and signs after topical cyclosporine treatment. Ophthalmology. 2007;114(1):76-79. doi: 10.1016/j.ophtha.2006.05.077.
• 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.
• Restasis. Prescribing Information. Allergan; 2012. Accessed July 8, 2024. http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/050790s020lbl.pdf
• 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.
• 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.
• 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.
• 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.
• The Relationship Between Dry Eye Disease and Digital Screen Use - PMC (nih.gov).
• Improved Dry Eye Drugs for 2022 and Beyond; https://www.aao.org/eye-health/tips-prevention/new-dry-eye-treatments-ocular-surface-disease.

 

[Paul Farkas]

An editorial comment in 5/31/25 Optometric Physician...

Off the Cuff: Nerves, Tears, and Working Our Way Upstream​ On Thursday another prescription dry eye medication entered the mix, with Alcon’s Tryptyr (acoltremon ophthalmic solution 0.003%), formerly known as AR-15512, receiving FDA approval. Tryptyr, which adds to a recent string of fantastically named dry eye medications, is a highly selective TRPM8 agonist that stimulates natural tear production using the basal tear pathway by binding TRPM8 receptors found on corneal nerve endings. I am particularly excited about this medication because of its therapeutic use of TRPM8. These receptors are the keys that essentially turn on basal tear production and make the lacrimal functional unit go. The cornea is the most heavily innervated structure in the body with nearly 7,000 nerve endings per square millimeter that sense numerous environmental stimuli. TRPM8 is a thermoreceptor that senses cooling—but not “cold” per se. The reason I make this distinction is because when most people think of cold and tearing, they think of the excessive tear production we get from walking outside on a blustery winter day which leaves our eyes dripping. That type of cold is a noxious stimulus and the tears produced are reflex tears, not basal tears, which is due to stimulation of a different receptor that senses extreme cold. TRPM8 receptors, on the other hand, sense slight changes in temperature, even changes as small as 1° C. Why does the cornea need a receptor that senses temperature changes this small? Like all things in physiology, it comes back to homeostasis. After blinking, the tear film sitting on the ocular surface will eventually evaporate and when it does, this produces a small drop in temperature. Think about why we sweat on a hot day or during exercise, because it produces a cooling effect as the sweat evaporates, pulling heat from the body. This evaporative cooling is how our body “knows,” so to speak, that we need to produce more tears—the tear film evaporates, resulting in a slight temperature drop on the ocular surface, this temperature reduction stimulates the TRPM8 receptors on the corneal nerves, which send a signal to the brainstem and brain, which, in turn, send signals to the lacrimal glands, meibomian glands, and goblet cells to produce the aqueous, lipid, and mucin components of the tear film, respectively, with the end result being the production of a complete basal tear. I remain in awe of how intricate, yet simple, this whole system is, and it all starts with the TRPM8 receptors. This makes TRPM8 the perfect treatment target. By binding the receptors and stimulating this basal tear pathway, Tryptyr leverages our natural tear production system. This also provides the benefit of treating dry eye relatively upstream in the disease process, as we can potentially address insufficient tear production before it results in the downstream effects of tear film instability, inflammation, and the dreaded “vicious cycle” of dry eye. I am excited to try Tryptyr in the wild when it becomes available, but, in the meantime, I am thrilled we are focusing on the neurological components of the ocular surface as we continue to work our way upstream in treating dry eye disease.

Cory J. Lappin, OD, MS, FAAO Chief Medical Editor coryjlappinod@gmail.com

 

[Dr. Stanley Hallock]

As originally approved....CAI glaucoma drops were TID....and once in the hands of independent researchers it was determined that BID was reasonable.
So............
Meibo is that frequent?
Restasis is BID?
This stuff is really BID?
Question everything