Aerie Pharmaceuticals doses first participant in COMET-2 study of dry eye candidate

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The Phase 3 registrational study is examining AR-15512, a differentiated, novel product candidate for the treatment of the signs and symptoms of Dry Eye Disease

Aerie Pharmaceuticals Inc. today announced that the first participant has been dosed in the Phase 3 registrational COMET-2 study to evaluate AR-15512 ophthalmic solution as a treatment for the signs and symptoms of dry eye disease (DED).

According to the company, COMET-2 (NCT05285644) is the first of three trials in the Phase 3 registrational program for AR-15512. The company said in a news release that it plans to initiate the other two trials in the second half of 2022 in support of a potential New Drug Application (NDA) filing in 2024.

AR-15512 is a first-in-class TRPM8 agonist which acts as a cold thermoreceptor modulator to stimulate the cold sensing receptors found on the nerve endings that innervate the cornea and eyelids. By stimulating these receptors, AR-15512 leads to natural tear production and a cooling sensation across the surface of the eye that may result in a reduction in dry eye symptoms. AR-15512 is a development stage product candidate and is not approved by any regulatory agency.

The company noted that COMET-2 is a randomly assigned, double-masked, vehicle-controlled, multi-center clinical study to evaluate the efficacy and safety of AR-15512, a TRPM8 agonist, in patients with DED.

The study is expected to enroll approximately 460 participants at 20 U.S. sites. Study participants will receive AR-15512 (0.003%) or AR-15512 vehicle as a drop dosed twice daily in each eye for three months. The primary efficacy assessment is tear production, as measured by the unanesthetized Schirmer test (sign), and the key secondary measure is dry eye symptoms based on the Symptom Assessment iN Dry Eye (SANDE) questionnaire.

The company noted that participants will be evaluated on multiple efficacy and safety assessments at multiple timepoints throughout the study. Topline results from the COMET-2 study are expected in the second half of 2023.

Michelle Senchyna, PhD, head of Clinical Development and Medical Affairs at Aerie, added in a news release that Aerie is excited to mark the beginning of its registrational Phase 3 program for AR-15512 with the enrollment of the first participant in the COMET-2 study.

“This study builds on the results of the COMET-1 study which showed statistically significant, dose-dependent improvements on multiple validated sign, symptom, and quality of life endpoints across multiple timepoints,” Senchyna said in a statement.

“There is a significant unmet need for an effective treatment that can provide a rapid and robust onset of efficacy, and meaningful relief of dry eye symptoms,” Senchyna added in the release. “AR-15512 has the potential to be the new standard of care for patients suffering from dry eye disease.”

According to the company, the AR-15512 Phase 3 registrational program is comprised of three studies, the COMET-2 and COMET-3 (NCT05360966) efficacy studies and the COMET-4 safety study, that will evaluate AR-15512 (0.003%) compared to AR-15512 vehicle in participants with DED.

COMET-2, which is currently enrolling, and COMET-3, which is expected to begin in the third quarter of 2022, are identical studies with topline results expected in the second half of 2023. COMET-4, which is expected to begin in the fourth quarter of 2022, is a 12-month safety study. Aerie will incorporate interim 6-month data from COMET-4 into the NDA filing for AR-15512, which is expected to be submitted in 2024.

The COMET-1 study (NCT04498182)evaluated two doses of AR-15512 compared to AR-15512 vehicle in 369 participants with DED. As reported in September 2021, the trial did not achieve Aerie’s previously chosen primary endpoints. The study showed a statistically significant, dose-dependent increase in tear production, a validated endpoint acceptable for registration of a product.

Moreover, the company noted in its release that AR-15512 demonstrated improvements on multiple validated sign, symptom, and quality of life endpoints across multiple timepoints. Importantly, the study showed that differences between AR-15512 and vehicle responses increased over time, indicating a potential sustained, meaningful treatment effect in DED signs and symptoms. COMET-1 demonstrated a favorable tolerability profile with no systemic or serious adverse events attributed to AR-15512.