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Remarks
Sepetaprost is a dual agonist of the FP and EP3 receptors. After ocular instillation, it is rapidly hydrolyzed by corneal esterases to its active metabolite, ONO-AG-367, which exhibits potent agonist activity at both FP and EP3 receptors. Unlike conventional FP receptor agonists (e.g., latanoprost), which selectively activate only the FP receptor, sepetaprost lowers intraocular pressure by simultaneously activating both pathways.
References
Suto F, et al. “A Novel Dual Agonist of EP3 and FP Receptors for OAG and OHT: Safety, Pharmacokinetics, and Pharmacodynamics of ONO-9054 in Healthy Volunteers.” Invest Ophthalmol Vis Sci. 2015 Dec;56(13):7963-70.
Wirta DL, et al. “Phase 2b, Randomized, 3-Month, Dose-Finding Study of Sepetaprost in Patients with Primary Open-Angle Glaucoma or Ocular Hypertension: The ANGEL Study.” J Ocul Pharmacol Ther. 2022 Apr;38(3):240-251.
Wirta DL, et al. “Sepetaprost 0.002% Noninferiority vs. Timolol 0.5% in Patients with Primary Open-Angle Glaucoma or Ocular Hypertension: ANGEL-2.” Ophthalmology Glaucoma. 2025 Jul-Aug;8(4):384-392.
Inatani M, et al. “Efficacy and safety of sepetaprost in patients with primary open-angle glaucoma or ocular hypertension: results from the randomised, phase 3 ANGEL-J1 study.” Jpn J Ophthalmol. 2026 Jul;70(4):957-965.
ANGEL-J2 Study: “Long-term safety and efficacy of sepetaprost, with or without timolol, in patients with open-angle glaucoma or ocular hypertension: results from the randomised, phase 3 ANGEL-J2 study.” Japanese Journal of Ophthalmology. 2026.
Konstas AG, et al. “A Study of 24-h Efficacy and Safety of Sepetaprost vs. Latanoprost in Patients with Primary Open-Angle Glaucoma or Ocular Hypertension.” Adv Ther. 2025 Jun 10;42(8):3810-3825.
Wu X, Yang X, Liang Q, et al. “Drugs for the treatment of glaucoma: Targets, structure-activity relationships and clinical research.” European Journal of Medicinal Chemistry. 2021;226:113842.