Acoltremon .003% Reduces Corneal Fluorescein Staining, Research Review Suggests

Acoltremon ophthalmic solution .003% (ACO) is safe and efficacious in treating total corneal fluorescein staining (tCFS) in patients with dry eye disease (DED), according to a post hoc analysis presented at the 2025 American Optometric Association Conference in Minneapolis, MN.

Acoltremon, approved to treat DED in May 2025, is a first-in-class TRPM8 receptor agonist, designed to rapidly stimulate natural tear production. During 2 pivotal phase 3 clinical trials, COMET-2 and COMET-3, patients prescribed acoltremon saw substantial increases in tear production and reduced tCFS.2

This recent post hoc analysis by Selina McGee, OD, founder, executive, and chief optometrist of BeSpoke Vision, and colleagues further investigates the clinical relevance of the effect of acoltremon – particularly ACO .003% - on corneal epithelial damage. The team analyzed data from the COMET-2 and COMET-3 trials.1

COMET-2 and 3 were both multicenter, vehicle-controlled, double-masked, randomized studies, each one conducted at roughly 20 sites across the US. COMET-2 included 465 patients with DED, while COMET-3 included 467. The trials consisted of a screening day, a baseline visit, and subsequent visits at days 7, 14, 28, and 90. Investigators in each trial administered one drop of either ACO .003% or vehicle in each eye for 90 days. Investigators primarily measured the unanesthetized Schirmer test results, with Symptom Assessment iN Dry Eye (SANDE) scores and ocular discomfort scores as secondary endpoints.3,4

McGee and colleagues included patients aged ≥30 years with a diagnosis of DED within 6 months who desire to use or have used artificial tears for DED symptoms. Additionally, patients had to have an ICFS score between ≥2 and ≥15, with no one region scoring >3 at screening onl,y and an anesthetized Schirmer score between ≥2 and <10 mm/5 min at both screening and baseline in at least one eye.1

Patients who had used any topical ocular anti-inflammatory medication or other topical ocular treatment for DED within 30 days of screening or during the study, or who had used artificial tears within 2 hours before screening or during the study, were excluded. Investigators also filtered out patients presenting with a history of ocular surgery within 1 year before screening and those who wore contact lenses within 7 days of screening.1

Investigators found that, in both COMET trials, a substantially greater proportion of patients treated with ACO .003% achieved ≥3 point reduction in tCFS compared to vehicle as early as day 7. Notable (P ≤.0295) proportion differences were observed from Day 14 through the end of both trials (range: 7.2% to 12.9%). Additionally, a greater proportion of patients treated with ACO .003% achieved ≥25% reduction in tCFS compared to VEH at all timepoints. Notable (P ≤.0325) proportion differences were observed at days 7, 28, and 90.1

Neither trial reported any serious ocular adverse events; the only treatment-emergent adverse event with >2.5% incidence associated with ACO .003% was mild and transient instillation site burning and stinging. Additionally, most patients reporting this event reported a duration of ≤1 minute.1

Ultimately, investigators found rapid and consistent tCFS reductions in both COMET trials, indicating a substantial improvement in ocular surface damage.1

“Overall, the efficacy of ACO as highlighted by rapid and persistent tear production combined with reduced DED symptoms and clinically relevant reductions in corneal staining, supports the potential of ACO as a new treatment option for the signs and symptoms of DED,” McGee and colleagues wrote.1

References

1. McGee S, et al. Post Hoc Analyses of Pooled Pivotal Data Support Clinically Relevant Reductions in Total Corneal Staining Associated with Acoltremon 0.003%. Abstract presented at the 2025 American Optometric Association Conference in Minneapolis, MN, June 25-28, 2025.

2. Alcon. Alcon Announces FDA Approval of TRYPTYR (acoltremon ophthalmic solution) 0.003% for the Treatment of the Signs and Symptoms of Dry Eye Disease. May 28, 2025. Accessed June 27, 2025. https://investor.alcon.com/news-and-events/press-releases/news-details/2025/Alcon-Announces-FDA-Approval-of-TRYPTYR-acoltremon-ophthalmic-solution-0-003-for-the-Treatment-of-the-Signs-and-Symptoms-of-Dry-Eye-Disease/default.aspx

3. Study Evaluating the Safety and Efficacy of AR-15512 (COMET-2). ClinicalTrials.gov identifier: NCT05285644. Updated July 18, 2024. Accessed June 27, 2025. https://clinicaltrials.gov/study/NCT05285644?term=COMET-2&rank=2

4. Study Evaluating the Safety and Efficacy of AR-15512 (COMET-3). ClinicalTrials.gov identifier: NCT05360966. Updated September 26, 2024. Accessed June 27, 2025. https://clinicaltrials.gov/study/NCT05360966?term=COMET-3&rank=1