Acoltremon Ophthalmic Solution 0.003% for Signs and Symptoms of Dry Eye Disease: Results of Phase 3 Pivotal COMET-2 and COMET-3 Studies

Abstract

Purpose: To evaluate the safety and efficacy of the transient receptor potential melastatin 8 agonist acoltremon on signs and symptoms of dry eye disease (DED).

Design: Two identical randomized, multicenter, double-masked, vehicle-controlled phase 3 studies.

Participants: Adults aged 30 years or older with a DED diagnosis, at least 1 eye with both total corneal fluorescein staining (tCFS) score of 2 or more and 15 or less (no region scoring less than 3) and anesthetized Schirmer test score of 2 or more and less than 10 mm/5 min, and both ocular discomfort (visual analog scale) and Symptom Assessment iN Dry Eye (SANDE) scores of 50 or more.

Methods: Patients (COMET-2, N = 465; COMET-3, N = 466) were randomized 1:1 to acoltremon 0.003% (ACO) or vehicle twice daily for 90 days (ClinicalTrials.gov identifiers: COMET-2, NCT05285644; COMET-3, NCT05360966).

Main outcome measures: The primary end point was the proportion of patients achieving a 10-mm or greater increase in unanesthetized Schirmer test (UST) score on day 14. The key secondary end point was change from baseline (CFB) in global SANDE score on day 28. Additional secondary end points included CFB in UST on days 1 and 90. Exploratory end points included CFB in tCFS and total conjunctival staining.

Results: The primary end point was met in both studies, with more patients receiving ACO achieving a 10-mm or greater increase in UST on day 14 (ACO vs. vehicle: COMET-2, 42.6% vs. 8.2%; COMET-3, 53.2% vs. 14.4%; P < 0.0001 for both). Reduction in global SANDE score by day 28 (key secondary end point) favored ACO in both studies, and was statistically significant in COMET-2. Increased tear production favored ACO versus vehicle as early as day 1 through day 90 in both studies (P < 0.0001). Greater reductions with ACO were observed in tCFS on days 28 and 90 and in total conjunctival staining at all time points. Mild instillation-site burning/stinging was the only ocular adverse event reported with an incidence of more than 2.5%.

Conclusions: In COMET-2 and COMET-3, ACO compared with vehicle led to consistent, clinically meaningful tear production and reductions in DED signs and symptoms.

Financial disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Keywords: Acoltremon; Dry eye disease; Ocular surface staining; TRPM8 agonist; Tear production.