FDA Approves Acoltremon Ophthalmic Solution for Dry Eye Disease
The new approval is for a first-in-class TRPM8 receptor agonist to stimulate corneal sensory nerves to increase natural tear production.
The FDA approved acoltremon ophthalmic solution (Tryptyr, formerly AR-15512) 0.003% for the treatment of dry eye disease (DED). The new approval is for a first-in-class TRPM8 receptor agonist to stimulate corneal sensory nerves to increase natural tear production.1
The new approval is for a first-in-class TRPM8 receptor agonist to stimulate corneal sensory nerves to increase natural tear production. | Image Credit: lenblr - stock.adobe.com
“Many of my patients continue to face frustrating challenges with dry eye management, and there is a clear need for additional treatment options,” Marjan Farid, MD, professor of ophthalmology at the University of California Irvine, said in a news release.1 “Tryptyr is the first eye drop that stimulates corneal nerves to directly address tear deficiency, a known cause of dry eye disease.”
The approval is supported by 2 phase 3 clinical trials, COMET-2 and COMET-3, which included more than 930 patients with a history of DED who received either the drug or a vehicle. The primary end point included the proportion of individuals with at least a 10-mm increase in unanesthetized Schirmer score. In both studies, investigators reported that the drug achieved statistical significance at day 14, supporting the proposed mechanism of action.1,2
Investigators found that 42.6% of patients in COMET-2 and 53.2% in COMET-3 who received the drug achieved the primary end point compared with 8.2% and 14.4%, respectively, with the vehicle. There were consistent results at all timepoints through day 90, according to the data. The drug also demonstrated statistically significant natural tear production as early as day 1.1
“A key gap in dry eye medications is rapid speed of onset,” Edward Holland, MD, professor of ophthalmology at the University of Cincinnati, a key advisor on COMET-2 and COMET-3, and senior scientific advisor at Alcon, said in a news release.2 “AR-15512 demonstrated this important achievement in both pivotal efficacy and safety studies, and it represents a first-in-class candidate for chronic dry eye.”
Previously, in a phase 2b study, patients with DED received randomized treatment 1:1:1 to 0.0014%, 0.003% AR-15512, or the vehicle twice daily for 12 weeks, according to the study authors. The co-primary end points included the changes from baseline in ODS-VAS and anesthetized Schirmer score at day 28. The investigators found that the 0.003% AR-15512 was associated with early and sustained improvements in unanesthetized Schirmer score at days 1 and 14 and improvement in ocular surface staining at days 14 and 84. Further, the study authors reported improvements in hyperemia at day 84, symptoms on Symptoms Assessment in Dry Eye at days 14, 28, and 84, ODS-VAS at day 84, Eye Dryness-VAS at day 84, and multiple quality of life measures at days 14, 28, and 84.3
Investigators also reported that there were no significant differences between the drug treatment groups and the vehicle groups for co-primary end points. The most common adverse events observed included burning and stinging at application.3
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REFERENCES
1. Alcon announces FDA approval of Tryptry (acoltremon ophthalmic solution) 0.003% for the treatment of the signs and symptoms of dry eye disease. News release. Alcon. May 28, 2025. Accessed May 29, 2025. https://www.businesswire.com/news/home/20250526316115/en/Alcon-Announces-FDA-Approval-of-TRYPTYR-acoltremon-ophthalmic-solution-0.003-for-the-Treatment-of-the-Signs-and-Symptoms-of-Dry-Eye-Disease
2. Alcon announces positive topline results from phase 3 COMET trials of AR-15512, a novel topical drug candidate for dry eye. News release. Alcon. January 9, 2024. Accessed May 29, 2025. https://www.alcon.com/media-release/alcon-announces-positive-topline-results-phase-3-comet-trials-ar-15512-novel-topical/
3. Wirta DL, Senchyna M, Lewis AE, et al. A randomized, vehicle-controlled, Phase 2b study of two concentrations of the TRPM8 receptor agonist AR-15512 in the treatment of dry eye disease (COMET-1). Ocul Surf. 2022;26:166-173. doi:10.1016/j.jtos.2022.08.003
