Efficacy and safety of sepetaprost in patients with primary open-angle glaucoma or ocular hypertension: results from the randomised, phase 3 ANGEL-J1 study

Purpose To evaluate the efficacy and safety of sepetaprost, a novel dual FP/EP3 receptor agonist, in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OHT). Study design ANGEL-J1 (NCT05495061) was a phase 3, randomised, investigator-masked, active-controlled, parallel-group, non-inferiority study across 49 sites in Japan. Methods Adults with POAG or OHT were randomised 1:1 to topical sepetaprost 0.002% or latanoprost 0.005%, once daily for 3 months. The primary endpoint was change in mean diurnal intraocular pressure (IOP) from baseline at week 4 (non-inferiority margin, 1.5 mmHg); a key secondary endpoint was mean change in IOP from baseline over 3 months. Safety outcomes included the incidence of adverse drug reactions (ADRs). Results In total, 325 patients were randomised to sepetaprost (n=162) or latanoprost (n=163). In mixed model for repeated measures analyses, ANGEL-J1 met its primary endpoint; the least-squares mean (± standard error) change in mean diurnal IOP from baseline at week 4 was −5.77±0.16 mmHg in the sepetaprost group, which was non-inferior to −6.10±0.16 mmHg in the latanoprost group (least-squares mean difference, 0.32 mmHg [95% confidence interval, −0.12, 0.77]). Non-inferiority for the key secondary endpoint was also established, with comparable mean reductions in IOP between groups maintained over 3 months. ADRs occurred in 59 patients (36.4%) receiving sepetaprost and 33 (20.2%) receiving latanoprost; the most common ADR was conjunctival hyperaemia (29.6% and 8.6%, respectively; mostly mild in severity). Conclusion In patients with POAG or OHT, sepetaprost demonstrated IOP-lowering efficacy that was non-inferior to latanoprost, and an acceptable safety profile.