Tryptyr (acoltremon ophthalmic solution) / Alcon - LARVOL DELTA

Current and emerging pharmacological treatment options for patients with dry eye disease. (PubMed, Expert Rev Clin Pharmacol) - "The recent FDA approval of AR-15512, a TRPM8 agonist, exemplifies the trend toward mechanism-specific therapies designed to deliver both symptomatic relief and disease modification. As the therapeutic armamentarium expands globally, continued clinical trials and real-world studies will be essential to ensure durable efficacy and optimize patient outcomes."

Journal • Review • Dry Eye Disease • Inflammation • Ocular Inflammation • Ophthalmology • TRPM8

Acoltremon: First Approval. (PubMed, Drugs) - "During phase III trials in patients with dry eye disease, acoltremon demonstrated increased tear production with a low treatment discontinuation rate. This article summarizes the milestones in the development of acoltremon leading to this first approval for the treatment of the signs and symptoms of dry eye disease."

Journal • Dry Eye Disease • Ophthalmology • TRPM8

Acoltremon. (PubMed, Am J Health Syst Pharm) - No abstract available

Journal

Acoltremon: The first TRPM8 agonist approved for the treatment of dry eye disease. (PubMed, Drug Discov Ther) - "Acoltremon has multiple advantages: rapid onset of action, significant alleviation of dry eye signs and symptoms, and favorable safety and tolerability. In summary, the approval of acoltremon represents a new therapeutic perspective on the management of DED."

Journal • Dry Eye Disease • Ophthalmology • Pain • TRPM8

Alcon Announces FDA Approval of TRYPTYR (acoltremon ophthalmic solution) 0.003% for the Treatment of the Signs and Symptoms of Dry Eye Disease (Businesswire) - "Alcon...announced the U.S. Food and Drug Administration (FDA) has approved TRYPTYR (acoltremon ophthalmic solution) 0.003%, formerly known as AR-15512, for the treatment of signs and symptoms of Dry Eye Disease (DED)....This approval is supported by two Phase 3 clinical trials evaluating more than 930 patients (randomized 1:1 to TRYPTYR or vehicle) with a history of DED. In COMET-2 and COMET-3, up to four times more TRYPTYR patients experienced at least a 10mm increase in natural tear production at Day 14, compared to vehicle, 42.6% versus 8.2% of patients in COMET-2 and 53.2% versus 14.4% in COMET-3 (both p<0.0001)."

FDA approval • Dry Eye Disease

Tear production with the novel TRPM8 agonist acoltremon: a phase 1 methodology study (ARVO 2025) - "Acoltremon (previously AR-15512) is a potent and highly selective TRPM8 agonist in development as a treatment option for dry eye disease (DED)...The most common adverse event in the study was mild instillation site burning/stinging, reported by 20% of subjects receiving acoltremon. These findings are consistent with the mechanism of acoltremon as an activator of the TRPM8 receptor, and suggest that future clinical studies with acoltremon are best performed in a real-world setting in the absence of topical anesthetic."

P1 data • Dry Eye Disease • Ophthalmology • TRPM8

A Study to Investigate the Effect of 0.003% AR-15512 on Subjects With Dry Eye Disease (clinicaltrials.gov) - P3 | N=79 | Completed | Sponsor: Alcon Research | Active, not recruiting ➔ Completed

Trial completion • Dry Eye Disease • Ophthalmology

A Study to Evaluate 0.003% AR-15512 Safety and Drop Attributes (clinicaltrials.gov) - P3 | N=55 | Completed | Sponsor: Alcon Research | Recruiting ➔ Completed

Trial completion • Dry Eye Disease • Ophthalmology

A Study Designed to Evaluate Tear Production (clinicaltrials.gov) - P3 | N=81 | Completed | Sponsor: Alcon Research | Recruiting ➔ Completed

Trial completion • Dry Eye Disease • Ophthalmology

A Study to Investigate the Effect of 0.003% AR-15512 on Subjects With Dry Eye Disease (clinicaltrials.gov) - P3 | N=79 | Active, not recruiting | Sponsor: Alcon Research | Recruiting ➔ Active, not recruiting

Enrollment closed • Dry Eye Disease • Ophthalmology

A Study to Evaluate 0.003% AR-15512 Safety and Drop Attributes (clinicaltrials.gov) - P3 | N=55 | Recruiting | Sponsor: Alcon Research | Not yet recruiting ➔ Recruiting

Enrollment open • Dry Eye Disease • Ophthalmology

A Study to Evaluate 0.003% AR-15512 Safety and Drop Attributes (clinicaltrials.gov) - P3 | N=55 | Not yet recruiting | Sponsor: Alcon Research

New P3 trial • Dry Eye Disease • Ophthalmology

A Study Designed to Evaluate Tear Production (clinicaltrials.gov) - P3 | N=80 | Recruiting | Sponsor: Alcon Research | Not yet recruiting ➔ Recruiting

Enrollment open • Dry Eye Disease • Ophthalmology

A Study to Investigate the Effect of 0.003% AR-15512 on Subjects With Dry Eye Disease (clinicaltrials.gov) - P3 | N=70 | Recruiting | Sponsor: Alcon Research | Not yet recruiting ➔ Recruiting

Enrollment open • Dry Eye Disease • Ophthalmology

AR-15512: A Novel TRPM8 Agonist for the Treatment of the Signs and Symptoms of Dry Eye: Phase 3 Pivotal Study Results (AAO 2024) - "Persistent production of basal tears led to DED symptom improvement, demonstrated by reduced SANDE scores in favor of 512. Data support 512 as a potential new option to rapidly and effectively treat signs and symptoms of DED."

P3 data • Dry Eye Disease • Ophthalmology • TRPM8

Ar-15512, A Novel Trpm8 Agonist For The Treatment Of The Signs And Symptoms Of Dry Eye Disease: Topline Efficacy And Safety Data From Phase 3 Pivotal Clinical Studies (Comet-2 And Comet-3) (ESCRS 2024) - No abstract available

Clinical • P3 data • P3 data: top line • Dry Eye Disease • Ophthalmology • TRPM8

A Study Designed to Evaluate Tear Production (clinicaltrials.gov) - P3 | N=80 | Not yet recruiting | Sponsor: Alcon Research

New P3 trial • Dry Eye Disease • Ophthalmology

A Study to Investigate the Effect of 0.003% AR-15512 on Subjects With Dry Eye Disease (clinicaltrials.gov) - P3 | N=70 | Not yet recruiting | Sponsor: Alcon Research

New P3 trial • Dry Eye Disease • Ophthalmology

COMET-1: A Phase 2b Study Evaluating the Safety and Efficacy of AR-15512 Ophthalmic Solution for the Treatment of Dry Eye Disease (clinicaltrials.gov) - P2 | N=369 | Completed | Sponsor: Aerie Pharmaceuticals | Phase classification: P2b ➔ P2

Phase classification • Dry Eye Disease • Ophthalmology

COMET-4: A Long-Term Safety Study Evaluating the Safety and Systemic Exposure of AR-15512 (clinicaltrials.gov) - P3 | N=275 | Completed | Sponsor: Aerie Pharmaceuticals | Active, not recruiting ➔ Completed

Trial completion • Dry Eye Disease • Ophthalmology

Study Evaluating the Safety and Efficacy of AR-15512 (COMET-3) (clinicaltrials.gov) - P3 | N=467 | Completed | Sponsor: Aerie Pharmaceuticals | Active, not recruiting ➔ Completed

Trial completion • Dry Eye Disease • Ophthalmology

COMET-2: Study Evaluating the Safety and Efficacy of AR-15512 (clinicaltrials.gov) - P3 | N=465 | Completed | Sponsor: Aerie Pharmaceuticals | Active, not recruiting ➔ Completed

Trial completion • Dry Eye Disease • Ophthalmology

Study Evaluating the Safety and Efficacy of AR-15512 (COMET-3) (clinicaltrials.gov) - P3 | N=467 | Active, not recruiting | Sponsor: Aerie Pharmaceuticals | Recruiting ➔ Active, not recruiting

Enrollment closed • Dry Eye Disease • Ophthalmology

COMET-2: Study Evaluating the Safety and Efficacy of AR-15512 (clinicaltrials.gov) - P3 | N=465 | Active, not recruiting | Sponsor: Aerie Pharmaceuticals | Recruiting ➔ Active, not recruiting

Enrollment closed • Dry Eye Disease • Ophthalmology

TRPM8 Agonists: A New Approach to Dry Eye Disease Treatment (ARVO 2023) - "Purpose AR-15512, (1 R ,2 S ,5 R )-N-(4-methoxyphenyl)- p -menthane carboxamide), a small molecule in Phase 3 clinical trials for treating Dry Eye disease, is a potent and long-lasting transient receptor potential melastatin 8 (TRPM8) ligand agonist...A potential new treatment for Dry Eye Disease is being evaluated to see if it will help releive the pain and irritation of patients who suffer from this disease. The treatment involves stimulating nerves in a very particular way to create a soothing effect."

Dry Eye Disease • Ophthalmology