Sepetaprost 0.002% Noninferiority vs. Timolol 0.5% in Patients with Primary Open-Angle Glaucoma or Ocular Hypertension: ANGEL-2.

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.