■ The novel investigational prodrug sepetaprost 0.002% given daily was shown to be statistically noninferior to twice-daily timolol 0.5% for lowering intraocular pressure (IOP) in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OHT), according to a poster presented at AAO 2022. Sepetaprost targets 2 prostaglandin receptors, FP and EP3, and was studied in the phase 2 ANGEL-2 trial, reported investigator David L. Wirta, MD. In the multicenter study, 323 adults aged ≥18 years with POAG or OHT were randomized to once-daily sepetaprost or twice-daily timolol in 1 eye. After a washout period of up to 35 days, patients took 1 drop of sepetaprost daily at 8:00 pm, while the timolol comparator group took 2 drops of timolol daily, one each at 8:00 am and 8:00 pm. IOP was measured at 3 timepoints at the visits on week 2, week 6, and month 3. The primary endpoint was the noninferiority of sepetaprost to timolol, established if the difference in mean IOP between the 2 groups was ≤1.5 mmHg at all 9 timepoints, and ≤1 mmHg for at least 5 out of 9 timepoints.

An IOP reduction was observed in the sepetaprost group by week 2, along with stable IOP lowering throughout the study. Sepetaprost was statistically noninferior to timolol at all specified timepoints and statistically superior to timolol, at 4:00 pm at week 2, week 6, and month 3.