Acoltremon

Acoltremon sold under the brand name Tryptyr, is a medication used for the treatment of dry eye syndrome.^[1] Acoltremon is a transient receptor potential melastatin 8 (TRPM8) thermoreceptor agonist.^[1] It is used as an eye drop.^[1]

Acoltremon

Molecular structure of acoltremon
3D representation of an acoltremon molecule
Clinical data
Trade names	Tryptyr
Other names	AVX-012, WS-12
AHFS/Drugs.com	Monograph
MedlinePlus	a625071
License data	US DailyMed: Acoltremon
Routes of administration	Eye drop
ATC code	None
Legal status
Legal status	US: ℞-only[1]
Identifiers
IUPAC name (1R,2S,5R)-N-(4-methoxyphenyl)-5-methyl-2-propan-2-ylcyclohexane-1-carboxamide
CAS Number	68489-09-8
PubChem CID	11266244
DrugBank	DB19202
ChemSpider	9441255
UNII	1L7BVT4Z4Z
KEGG	D13125
ChEMBL	ChEMBL2441929
CompTox Dashboard (EPA)	DTXSID10460636
Chemical and physical data
Formula	C18H27NO2
Molar mass	289.419 g·mol−1
3D model (JSmol)	Interactive image
SMILES C[C@@H]1CC[C@H]([C@@H](C1)C(=O)NC2=CC=C(C=C2)OC)C(C)C
InChI InChI=1S/C18H27NO2/c1-12(2)16-10-5-13(3)11-17(16)18(20)19-14-6-8-15(21-4)9-7-14/h6-9,12-13,16-17H,5,10-11H2,1-4H3,(H,19,20)/t13-,16+,17-/m1/s1 Key:HNSGVPAAXJJOPQ-XOKHGSTOSA-N

The most common treatment-emergent adverse event experienced during the clinical studies was instillation site pain (burning or stinging) events.^[2]

Acoltremon was approved for medical use in the United States in May 2025.^[2]

Medical uses

Acoltremon is indicated for the treatment of the signs and symptoms of dry eye disease.^[1][2]

Pharmacology

Acoltremon acts as a potent and selective activator (opener) of the TRPM8 calcium channel, which is responsible for the sensation of coldness produced by menthol.^[3] It is slightly less potent as a TRPM8 activator compared to icilin, but is a much more selective TRPM8 ligand when compared to menthol.^[4]

History

The US Food and Drug Administration (FDA) approved acoltremon based on evidence from two clinical trials (COMET-2 and COMET-3) of 931 participants with dry eye disease.^[2] The trials were conducted at 46 sites in the United States.^[2] Two additional studies: COMET-1 and COMET-4 were included in the evaluation of safety benefit of acoltremon.^[2] The number of participants representing efficacy findings may differ from the number of participants representing safety findings due to different pools of study participants analyzed for efficacy and safety.^[2] Both COMET-2 and COMET-3 are phase III, multi-center, vehicle-controlled, double-masked, randomized studies whose primary endpoint was proportion of participants with ≥10 mm increase from baseline in unanesthetized Schirmer Score on day 14.^[2] COMET-1 was a phase IIb multi-center, vehicle-controlled, double-masked, randomized study conducted at 15 sites in the United States which randomized 369 participants with a history of dry eye disease.^[2] COMET-4 was a multi-center, vehicle-controlled, double-masked, randomized study conducted at approximately 10 sites in the United States which enrolled 275 participants with a history of dry eye disease.^[2] Study COMET-2 and COMET-3 have a similar design.^[2] Each study is a multi-center, randomized, double-masked, vehicle-controlled phase III study.^[2] The primary objective of these studies was to evaluate the safety and efficacy of acoltremon compared to vehicle.^[2] Participants 30 years and older with a history of artificial tear use for dry eye disease were qualified based on signs and symptoms of dry eye disease at screening, and were requalified at baseline (day 1) following a 14-day vehicle run-in.^[2] COMET 2 enrolled 465 participants at 23 study sites, whereas COMET-3 enrolled 466 participants at 23 sites.^[2]

Society and culture

Legal status

Acoltremon was approved for medical use in the United States in May 2025.^[5]

Names

Acoltremon is the international nonproprietary name.^[6]

Acoltremon is sold under the brand name Tryptyr.^[2]