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.

Abstract

Purpose: To evaluate the long-term safety and intraocular pressure (IOP)-lowering efficacy of sepetaprost, a novel dual FP/EP3 receptor agonist, in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT).

Study design: ANGEL-J2 (NCT05503901) was a phase 3, randomised, parallel-group, open-label study across 20 sites in Japan.

Methods: Adult patients with IOP ≥16 and <22 mmHg were assigned to once-daily sepetaprost 0.002% (Group 1), whereas patients with IOP ≥22 and ≤34 mmHg were randomised 1:1 to once-daily sepetaprost 0.002% alone (Group 2) and with twice-daily timolol 0.5% (Group 3). Over 52 weeks of treatment, efficacy was assessed as the change in mean diurnal IOP from baseline; safety outcomes included the incidence of adverse drug reactions (ADRs).

Results: In total, 131 patients were assigned to Group 1 (n=49), Group 2 (n=42), or Group 3 (n=40). In each group, treatment was associated with rapid and sustained reductions in IOP versus baseline (p<0.0001 at all time-points). Mean (± standard error) change in diurnal IOP from baseline at week 52 was -4.40±0.24, -6.38±0.32, and -7.51±0.29 mmHg in Groups 1, 2, and 3, respectively; similarly, mixed model for repeated measures analyses found that reductions in mean diurnal IOP over 52 weeks were greater in Group 3 versus Group 2. ADRs were reported in 80 patients overall (59.2-65.0% across groups), most commonly mild eyelash growth (22.4-42.5%) and mild conjunctival hyperaemia (28.6-30.6%).

Conclusion: Sepetaprost, with or without timolol, demonstrated good tolerability and may represent an efficacious long-term treatment option for OAG or OHT.