Although predefined co-primary study endpoints were not met, AR-15512 demonstrated statistically significant improvements in DED signs, symptoms, and disease-related quality of life.
Aerie Pharmaceuticals has published the results of its COMET-1 Phase 2b study of AR-15512, a transient receptor potential melastatin 8 (TRPM8) agonist, which is being evaluated as a potential therapy for DED.
The results were published this month in The Ocular Surface.1
According to the company, in a Phase 2b study, patients with DED were randomly assigned 1:1:1 to 0.0014% AR-15512, 0.003% AR-15512, or vehicle twice daily for 12 weeks. Eligibility criteria included DED signs and symptoms of prespecified severity levels. Outcomes assessed were DED signs (Schirmer score ± anesthetic, ocular surface staining, hyperemia), symptoms (Ocular Discomfort [ODS-VAS], Symptoms Assessment iN Dry Eye [SANDE], Eye Dryness-VAS, Ocular Pain-VAS), QoL-VAS, and adverse events. Co-primary endpoints were changes from baseline in ODS-VAS and anesthetized Schirmer score at Day 28.
According to the company, 0.003% AR-15512 (n = 122) was associated with early and sustained improvements in unanesthetized Schirmer score (Days 1 and 14, p < 0.0001), as well as improvements in ocular surface staining (Days 14 and 84, p ≤ 0.0365) and hyperemia (Day 84, p < 0.0215). Statistically significant improvements in symptoms were observed for the 0.003% concentration on SANDE (Days 14, 28, and 84, p ≤ 0.0254), ODS-VAS (Day 84, p = 0.0281), Eye Dryness-VAS (Day 84, p = 0.0302), and multiple QoL measures (Days 14, 28, and 84, p < 0.05).
There were no significant differences between active and vehicle groups for the co-primary endpoints. The most common adverse events were burning and stinging upon instillation.
Although predefined co-primary study endpoints were not met, AR-15512 demonstrated statistically significant improvements in DED signs, symptoms, and disease-related QoL.
Earlier this month, Aerie announced that the first participant has been dosed in the Phase 3 registrational “COMET-3” study to evaluate AR-15512 ophthalmic solution for the treatment of DED.
According to the company, COMET-3 is the second of three trials in the Phase 3 registrational program for AR-15512. Aerie plans to initiate the last of the trials, the COMET-4 safety study, in the fourth quarter of 2022. Aerie intends to complete the AR-15512 registrational program in 2023 and, assuming clinical success, plans to file a New Drug Application (NDA) with the FDA in 2024.
Michelle Senchyna, PhD, head of Clinical Development and Medical Affairs at Aerie, noted at that time that the company was glad to see he first participant enrolled in the COMET-3 study.
“The COMET program has strong momentum, driven by the effective collaboration with the COMET-2 and COMET-3 investigators,” she said in a news release. “The clinical data from the COMET-1 study showed statistically significant, dose-dependent improvements on multiple validated sign, symptom, and quality of life endpoints across multiple timepoints that informed our selection of the proper dose, primary and secondary endpoints and inclusion/exclusion criteria for the Phase 3 program.”
With enrollment now underway in both registrational efficacy studies, Senchyna said the company remains on track to announce top-line results for both studies in the second half of 2023.
David L. Wirta, MD; Michelle Senchyna, PhD; 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). The Ocular Surface, published August 13, 2022. https://doi.org/10.1016/j.jtos.2022.08.003