The U.S. Food and Drug Administration has approved Tryptyr (acoltremon ophthalmic solution) 0.003% for the treatment of signs and symptoms of dry eye disease, marking a significant milestone as the first-in-class TRPM8 receptor agonist to reach the market. Developed by Alcon, the treatment represents a novel approach to addressing tear deficiency by stimulating corneal sensory nerves to rapidly increase natural tear production.
Clinical Trial Results Demonstrate Rapid Efficacy
The FDA approval is supported by robust data from two Phase 3 clinical trials, COMET-2 and COMET-3, which evaluated more than 930 patients with a history of dry eye disease. Participants were randomized 1:1 to receive either Tryptyr or vehicle control.
The results showed compelling efficacy across both studies. In COMET-2, 42.6% of Tryptyr patients experienced at least a 10mm increase in natural tear production at Day 14, compared to only 8.2% of patients receiving vehicle (p<0.0001). Similarly, in COMET-3, 53.2% of Tryptyr patients achieved this endpoint versus 14.4% in the vehicle group (p<0.0001). This represents up to four times more patients responding to treatment compared to placebo.
Notably, Tryptyr demonstrated statistically significant natural tear production as early as Day 1, with consistent results observed at all timepoints through Day 90. This rapid onset of action addresses a key limitation of existing dry eye treatments, which often have slow onset and contribute to patient dissatisfaction.
Novel Mechanism of Action
Tryptyr works through a unique mechanism as a TRPM8 receptor agonist. Animal studies suggest that acoltremon, the active substance in Tryptyr, acts as 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.
"Tryptyr is the first eye drop that stimulates corneal nerves to directly address tear deficiency, a known cause of Dry Eye Disease," said Marjan Farid, MD, Professor of Ophthalmology at the University of California, Irvine.
Addressing Significant Unmet Medical Need
Dry eye disease affects an estimated 38 million adults in the U.S. and 719 million adults globally, making it one of the most common ocular surface disorders. The condition is characterized by a deficiency in natural tears due to either decreased tear production or increased tear evaporation.
Current treatment options face significant limitations. Among surveyed dry eye patients, only 13% felt their dry eye was well managed. The disease significantly impacts patients' daily lives, with 56% of survey respondents reporting negative effects on their ability to drive at night, 42% experiencing difficulties reading, 34% having trouble using computers, and 24% finding it affects their ability to watch television.
Many commonly used dry eye disease treatment options have limitations including slow onset, patient dissatisfaction, and poor adherence. Despite the high prevalence, less than 10% of diagnosed patients are currently being treated with a prescription product, highlighting the substantial treatment gap.
Safety Profile and Administration
In clinical trials, the most common adverse reaction was instillation site pain, occurring in 50% of patients. Tryptyr is contraindicated for use while wearing contact lenses, though lenses may be reinserted 15 minutes following administration.
The treatment is available in easy-to-use, single-dose vials with a dosing regimen of one drop per eye, twice daily. Patients should be advised not to touch the vial tip to the eye or other surfaces to avoid potential eye injury and contamination.
Commercial Launch and Market Impact
"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."
Alcon expects to launch Tryptyr in the U.S. during the third quarter of 2025 and anticipates bringing the treatment to other markets in the future. The approval positions Alcon to compete in the dry eye treatment market alongside existing FDA-approved treatments including Alcon's own Eysuvis and Bausch + Lomb's Xiidra.
The company is betting on new product launches like Tryptyr to accelerate sales growth in the second half of 2025 and beyond, as it continues to expand its portfolio beyond surgical and vision care products into prescription pharmaceuticals.
