Delving into the Latest Updates on Sepetaprost with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

+ [1]

Target

EP3 x PTGFR

Mechanism

EP3 agonists(Prostanoid EP3 receptor agonists), PTGFR agonists(Prostanoid FP receptor agonists)

Therapeutic Areas

Eye Diseases

Active Indication

Glaucoma 1, Open Angle, A

Inactive Indication-

Originator Organization

Ono Pharmaceutical Co., Ltd.

Active Organization

Santen Pharmaceutical Co., Ltd.

Inactive Organization

Ono Pharma USA, Inc.

Ono Pharmaceutical Co., Ltd.

Drug Highest PhasePhase 3

First Approval Date-

Regulation-

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Structure

Molecular FormulaC26H36F2O6

InChIKeyBKVUSNOUTQMSBE-XCMGCKIWSA-N

CAS Registry1262873-06-2

INTRODUCTIONGlaucoma is a leading cause of blindness with intraocular pressure (IOP) as the only known modifiable risk factor. Prostaglandin FP receptor agonists are the first-line medical treatment for glaucoma and ocular hypertension. Despite their efficacy, their IOP lowering effect may be insufficient requiring second agents, and poor patient compliance to medical therapy may preclude their full effect.AREAS COVEREDThis literature review examines the novel FP receptor drugs and drug delivery devices in clinical phase trials for treatment of glaucoma. Three novel drugs targeting FP receptors were identified, including latanoprostene bunod, NCX 470, and sepetaprost. Additionally, sustained drug delivery devices in early clinical phase trials included intracameral implants, punctal plugs, ocular rings, and contact lenses.EXPERT OPINIONNO hybrid FP receptor agonists and dual FP/EP3 receptor agonists may show promise as novel medical therapies with greater efficacy than approved prostaglandin analogs in clinical use, with a similar safety profile. Alternatively, drug delivery systems may provide a similar IOP lowering effect to existing agonists but overcome issues with patient compliance and convenience. A personalized approach to drug delivery devices may be required to ensure the most appropriate fit for the patient according to the invasiveness and duration of therapy desired.

01 Apr 2023·Experimental Eye Research

FP and EP2 prostanoid receptor agonist drugs and aqueous humor outflow devices for treating ocular hypertension and glaucoma

Review

Author: Sharif, Najam A ; Pinchuk, Leonard ; Lu, Fenghe ; Odani-Kawabata, Noriko

Prostaglandin (PG) receptors represent important druggable targets due to the many diverse actions of PGs in the body. From an ocular perspective, the discovery, development, and health agency approvals of prostaglandin F (FP) receptor agonists (FPAs) have revolutionized the medical treatment of ocular hypertension (OHT) and glaucoma. FPAs, such as latanoprost, travoprost, bimatoprost, and tafluprost, powerfully lower and control intraocular pressure (IOP), and became first-line therapeutics to treat this leading cause of blindness in the late 1990s to early 2000s. More recently, a latanoprost-nitric oxide (NO) donor conjugate, latanoprostene bunod, and a novel FP/EP3 receptor dual agonist, sepetaprost (ONO-9054 or DE-126), have also demonstrated robust IOP-reducing activity. Moreover, a selective non-PG prostanoid EP2 receptor agonist, omidenepag isopropyl (OMDI), was discovered, characterized, and has been approved in the United States, Japan and several other Asian countries for treating OHT/glaucoma. FPAs primarily enhance uveoscleral (UVSC) outflow of aqueous humor (AQH) to reduce IOP, but cause darkening of the iris and periorbital skin, uneven thickening and elongation of eyelashes, and deepening of the upper eyelid sulcus during chronic treatment. In contrast, OMDI lowers and controls IOP by activation of both the UVSC and trabecular meshwork outflow pathways, and it has a lower propensity to induce the aforementioned FPA-induced ocular side effects. Another means to address OHT is to physically promote the drainage of the AQH from the anterior chamber of the eye of patients with OHT/glaucoma. This has successfully been achieved by the recent approval and introduction of miniature devices into the anterior chamber by minimally invasive glaucoma surgeries. This review covers the three major aspects mentioned above to highlight the etiology of OHT/glaucoma, and the pharmacotherapeutics and devices that can be used to combat this blinding ocular disease.

01 Apr 2022·Journal of Ocular Pharmacology and TherapeuticsQ4 · MEDICINE

Phase 2b, Randomized, 3-Month, Dose-Finding Study of Sepetaprost in Patients with Primary Open-Angle Glaucoma or Ocular Hypertension: The ANGEL Study

Q4 · MEDICINE

Article

Author: Odani-Kawabata, Noriko ; Wirta, David L. ; Lu, Fenghe ; Kuwayama, Yasuaki ; Shao, Hui

Purpose: This phase 2b, randomized, observer-masked, placebo- and active-controlled, parallel-group, multinational (USA and Japan), multicenter study (NCT03216902) assessed the optimal dose of sepetaprost ophthalmic solution in patients with primary open-angle glaucoma or ocular hypertension. Methods: After washout, patients ≥18 years (USA) or ≥20 years of age (Japan) received once-daily sepetaprost for 3 months [0.0005% (n = 43); 0.001% (n = 43); 0.002% (n = 44); and 0.003% (n = 45)], latanoprost 0.005% (n = 44) or placebo until week 6, followed by sepetaprost 0.003% until month 3 (n = 22). Safety assessments included adverse event (AE) occurrence. Results: Baseline mean diurnal intraocular pressure (IOP) was 24.3 mmHg for latanoprost and ranged between 24.1 and 24.5 mmHg for the sepetaprost groups. Sepetaprost 0.002% had the lowest IOP at each month 3 time point (9:00 AM; 1:00 PM; 5:00 PM) of all sepetaprost concentrations (mean ± standard error: 17.6 ± 0.5; 17.4 ± 0.4; 16.7 ± 0.4 mmHg); similar values were observed with latanoprost (18.1 ± 0.6; 17.3 ± 0.5; 17.2 ± 0.5 mmHg). A positive dose-response relationship was observed with the 3 lower sepetaprost doses; sepetaprost 0.002% had numerically greater IOP-lowering effects than sepetaprost 0.003%. All sepetaprost doses had statistically significantly greater IOP reductions from baseline versus placebo at week 6 (P < 0.0001). This IOP-lowering effect was consistent between Japan- and USA-based patients. Most AEs were mild and occurred numerically less frequently with sepetaprost 0.002% (34.1%) versus latanoprost (50.0%). The most frequently reported AE was conjunctival hyperemia. Conclusion: In this study, sepetaprost 0.002% was the optimal concentration, showing comparable IOP-lowering efficacy and safety with latanoprost 0.005%. Most AEs were mild; occurrence was numerically lower with sepetaprost 0.002% than latanoprost 0.005%.

100 Deals associated with Sepetaprost

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB12043

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Glaucoma 1, Open Angle, A	Phase 3	JP	Santen Pharmaceutical Co., Ltd.	09 Aug 2022
Glaucoma, Open-Angle	Discovery	US	Ono Pharmaceutical Co., Ltd.	01 May 2014

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04742283 (ANGEL-2, CTgov)	Phase 2	Glaucoma, Open-Angle	323	Timolol Maleate Ophthalmic Solution 0.5% BID (Timolol Maleate Opthalmic Solution 0.5% BID)	kattbwgpiz(etsyuwspuj) = bajsbqeuts vbwmatnpcu (yajiqseodu, qnnuhgitbi - eeilznnrwx) View more	-	26 Jan 2023
				DE-126 Ophthalmic Solution 0.002% QD (DE-126 Opthalmic Solution 0.002% QD and Vehicle QD)	kattbwgpiz(etsyuwspuj) = vlqgqkyyfz vbwmatnpcu (yajiqseodu, bptmhtgvhr - tvrjghnksh) View more
NCT03216902 (Angel Study, Pubmed) Manual	Phase 2	Ocular Hypertension \| Glaucoma, Open-Angle	174	Sepetaprost	(ygqxiqfxug) = ejxwhmkiqt nkpwisgaps (zaokzvxtnz )	Positive	15 Feb 2022
				latanoprost	(ygqxiqfxug) = llatgjzerz nkpwisgaps (zaokzvxtnz )
NCT02083289 (Pubmed \| Br J Ophthalmol) Manual	Phase 2	Ocular Hypertension \| Glaucoma, Open-Angle	123	ONO-9054	(kepbqpckhf) = rgzabpusvy anzjfwuadn (kjhivasato ) View more	Positive	01 Jun 2017
				Latanoprost	(kepbqpckhf) = tccznpdahl anzjfwuadn (kjhivasato )
NCT01670266 (Pubmed \| Br J Ophthalmol) Manual	Phase 1	Ocular Hypertension \| Glaucoma, Open-Angle	12	Placebo+ONO-9054 (AM dosing)	(iyjtqbqbnu) = mild ocular hyperaemia（6 pts），mild-moderate dryness thiefvwiry (qwndqylpwo )	Positive	01 Jun 2016
				Placebo+ONO-9054 (PM dosing)
ARVO2016	Phase 2	Glaucoma, Open-Angle \| Ocular Hypertension	-	ONO-9054 (0.003%, 30 μg/mL)	(mcceyqsyng) = the number of hyperemia AEs reported for ONO-9054 was higher than reported for Xalatan® (19.4% vs 8.2%) iubpieuijv (tmjozklxyw )	Positive	01 May 2016
				Xalatan® (0.005%, 50 μg/mL)
NCT01508988 (Pubmed \| Invest Ophthalmol Vis Sci) Manual	Phase 1	Glaucoma, Open-Angle \| Ocular Hypertension	48	ONO-9054	(gmurorqali) = yzqoszjsqb pqidsyrfmn (orxxnrromj )	Positive	01 Dec 2015
				Placebo	-
ARVO2013	Not Applicable	-	-	ONO-9054	(lhnobjvbyk) = vcnwruflkp fuqfaevpih (qlhmguyjqo )	-	01 Jun 2013