SEPETAPROST

Sepetaprost, developed by Santen and Ono Pharmaceuticals, is sold as Setaneo ophthalmic solution 0.002% as a once-daily eyedrop to reduce elevated intraocular pressure (IOP) in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OHT). 

Sepetaprost is a novel investigative prodrug. It is a bicyclic prostaglandin derivative. The active form binds to and stimulates FP and EP3 receptors, promoting aqueous humor outflow and thereby lowering intraocular pressure (IOP). By activating both receptors, it increases the outflow of aqueous humor from the eye more effectively than traditional first-line prostaglandin analogs.

Clinical studies have shown that Sepetaprost 0.002% provides sustained IOP reduction consistently over 24-hours.

Comparisons with Timolol and Latanoprost have shown noninferior or superior efficacy of Sepetaprost. [1,2]

Conjunctival hyperemia (redness of the eye) is the most frequently reported ocular side effect. The majority of reported adverse reactions were considered mild to moderate, with no unexpected systemic safety concerns observed.

CLINICAL STUDIES 

1. The ANGEL-2 Study:

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

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.

REFERENCE:

Wirta DL, El-Harazi SM, Tepedino ME, Bacharach J. Sepetaprost 0.002% Noninferiority vs. Timolol 0.5% in Patients with Primary Open-Angle Glaucoma or Ocular Hypertension: ANGEL-2. Ophthalmol Glaucoma. 2025 Jul-Aug;8(4):384-392. doi: 10.1016/j.ogla.2025.02.004. Epub 2025 Mar 4. PMID: 40043909.

2. In another study, 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.

Conclusions: 

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.

REFERENCE:

Konstas AG, Garhöfer G, Lübke J, Voykov B, Ropo A. 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 Aug;42(8):3810-3825. doi: 10.1007/s12325-025-03227-2. Epub 2025 Jun 10. PMID: 40493333; PMCID: PMC12313740.