Delving into the Latest Updates on Sepetaprost with Synapse

In this exploratory study (EudraCT 2020-004836-93), adults with primary open-angle glaucoma (POAG) or ocular hypertension (OHT) were randomized to sepetaprost or latanoprost for 3 months following a ≤ 35-day screening period. The primary endpoint was mean 24-h intraocular pressure (IOP) at month 3 with sepetaprost vs. latanoprost. Safety outcomes included rate of adverse events (AEs).

RESULTS:

Overall, 33 participants received treatment (sepetaprost, n = 17; latanoprost, n = 16). Mean 24-h IOP was numerically lower with sepetaprost vs. latanoprost at month 3 (- 0.88 mmHg; 95% confidence interval [CI] - 2.89, 1.14; not statistically significant at the 0.05 level [NS]). Mean change from baseline in IOP at month 3 ranged from - 5.63 to - 7.00 mmHg for sepetaprost and - 3.84 to - 6.66 mmHg for latanoprost. Lower nocturnal IOP was observed with sepetaprost vs. latanoprost at month 3 (- 1.61 mmHg difference; 95% CI - 4.05, 0.83; not statistically significant; however, the 90% CI was - 5.27, - 0.17 and therefore, nominal statistical significance was achieved at the 0.10 level). Mean difference between groups indicated similar, or numerically lower, IOP with sepetaprost at individual time points at week 6 and month 3. At 36 and 48 h following sepetaprost cessation, mean IOP was lower vs. baseline IOP at the same time points. AEs occurred in 13 (76.5%) vs. 11 (68.8%) participants treated with sepetaprost vs. latanoprost.

CONCLUSION:

In participants with POAG or OHT, mean 24-h IOP and nocturnal IOP at month 3 were consistently numerically lower with sepetaprost vs. latanoprost. Safety profiles were similar between groups.

TRIAL REGISTRATION:

EudraCT 2020-004836-93.

01 Mar 2025·Ophthalmology Glaucoma

Sepetaprost 0.002% Noninferiority vs. Timolol 0.5% in Patients with Primary Open-Angle Glaucoma or Ocular Hypertension

Article

Author: Bacharach, Jason ; Wirta, David L ; El-Harazi, Sherif M ; Tepedino, Michael E

PURPOSE:

Sepetaprost is a novel investigative prodrug, the active form of which is a dual agonist targeting both prostaglandin F receptors and prostaglandin E receptor 3. This study (NCT04742283) aimed to demonstrate the noninferiority of sepetaprost ophthalmic solution 0.002% to timolol maleate ophthalmic solution 0.5% in participants with primary open-angle glaucoma (POAG) or ocular hypertension (OHT).

DESIGN:

A phase IIb, randomized, double-masked, active-controlled, multicenter study conducted in the United States.

PARTICIPANTS:

In total, 323 adult (≥18 years) participants (POAG, 68.4%; OHT, 31.6%) were randomized 1:1 to receive either once-daily sepetaprost (n = 162) or twice-daily timolol (n = 161) in 1 eye for 3 months.

METHODS:

Intraocular pressure (IOP) was measured at 3 timepoints (8:00 am, 10:00 am, and 4:00 pm) at 3 visits (weeks 2 and 6 and month 3).

MAIN OUTCOME MEASURES:

The primary efficacy endpoint was noninferiority of sepetaprost to timolol. Noninferiority was established if the upper limit of the 2-sided 95% confidence interval (CI) for the difference in mean IOP (sepetaprost minus timolol) was ≤1.5 mmHg at all 9 specified timepoints and ≤1.0 mmHg at 5 or more of the 9 timepoints. Superiority was tested if noninferiority was achieved. Safety, including adverse events (AEs) and suspected adverse reactions, was evaluated throughout.

RESULTS:

The primary endpoint, the noninferiority of sepetaprost to timolol in mean IOP reductions, was met. The upper limit of the 2-sided 95% CI for the between-group difference in mean IOP score was <1.0 mmHg at all 9 timepoints. Superiority of sepetaprost to timolol was observed at 4:00 pm in week 2, week 6, and month 3; IOP mean difference (standard error): -0.76 (0.302), -0.73 (0.328), and -0.95 (0.319), respectively (all P < 0.05). Overall, 23.6% of participants receiving sepetaprost and 21.3% receiving timolol experienced AEs. The most commonly reported ocular AE in both groups was conjunctival hyperemia (sepetaprost, 9.9%; timolol, 2.5%).

CONCLUSIONS:

Once-daily sepetaprost 0.002% was statistically noninferior to twice-daily timolol 0.5% for lowering IOP in participants with POAG or OHT. There were no unexpected safety concerns observed, and all AEs were mild or moderate in severity.

FINANCIAL DISCLOSURE(S):

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

02 Nov 2023·Expert opinion on investigational drugs

Prostaglandin FP receptor agonists in the treatment of glaucoma and ocular hypertension: a literature review

Review

Author: Moshegov, Sophia ; Kerr, Nathan Mitchell

INTRODUCTION:

Glaucoma 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 COVERED:

This 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 OPINION:

NO 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.

100 Deals associated with Sepetaprost

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External Link

KEGG	Wiki	ATC	Drug Bank
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R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Glaucoma	Japan	Santen Pharmaceutical Co., Ltd.	25 Aug 2025
Ocular Hypertension	Japan	Santen Pharmaceutical Co., Ltd.	25 Aug 2025

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Glaucoma, Open-Angle	Phase 3	Japan	Santen Pharmaceutical Co., Ltd.	08 Aug 2022

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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 (Timolol Maleate Opthalmic Solution 0.5% BID)	bqwmavcivw(xsvhchqzkx) = scpfyrcfvi jablauvkao (njggcnultk, 0.242) View more	-	26 Jan 2023
				DE-126 Ophthalmic Solution 0.002% QD (DE-126 Opthalmic Solution 0.002% QD and Vehicle QD)	bqwmavcivw(xsvhchqzkx) = litbqecchj jablauvkao (njggcnultk, 0.239) View more
NCT03216902 (Angel Study, Pubmed) Manual	Phase 2	Ocular Hypertension \| Glaucoma, Open-Angle	174	Sepetaprost	xsrttuivwv(pozqcxjknu) = vnnlmvwqoe knrwwanspn (nhsxfrecdj )	Positive	15 Feb 2022
				latanoprost	xsrttuivwv(pozqcxjknu) = lfywlsjarr knrwwanspn (nhsxfrecdj )
NCT02083289 (Pubmed \| Br J Ophthalmol) Manual	Phase 2	Ocular Hypertension \| Glaucoma, Open-Angle	123	ONO-9054	avluimferz(stzwnjdnro) = jatbsnszhq xzpskoiute (bwnxavkffa ) View more	Positive	01 Jun 2017
				Latanoprost	avluimferz(stzwnjdnro) = qvtqgvijnt xzpskoiute (bwnxavkffa )
NCT01670266 (Pubmed \| Br J Ophthalmol) Manual	Phase 1	Ocular Hypertension \| Glaucoma, Open-Angle	12	Placebo+ONO-9054 (AM dosing)	oqtvzjmbht(dloabwitwp) = mild ocular hyperaemia（6 pts），mild-moderate dryness nignnvqgxt (cuhneeynxu )	Positive	01 Jun 2016
				Placebo+ONO-9054 (PM dosing)
ARVO2016	Phase 2	Glaucoma, Open-Angle \| Ocular Hypertension	-	ONO-9054 (0.003%, 30 μg/mL)	tknwgjiwtw(bmwytvahxq) = the number of hyperemia AEs reported for ONO-9054 was higher than reported for Xalatan® (19.4% vs 8.2%) ndgygfgnqe (yzvclmcofe )	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	bztzzmurdq(yvqfbgshcd) = nwpqxtfevi dvjfsmqghk (yrotezfbyl )	Positive	01 Dec 2015
				Placebo	-