Aerpio Pharmaceuticals announced new results from the fifth cohort of subjects from a phase 1b trial of a topical ocular formulation of Tie2 activator AKB-9778, providing evidence of tolerability and IOP reduction from patients in that cohort with ocular hypertension (OHT) or primary open angle glaucoma (POAG).

AKB-9778 binds to and inhibits vascular endothelial protein tyrosine phosphatase (VE-PTP), an important negative regulator of Tie2. Decreased Tie2 activity contributes to vascular instability in many diseases including diabetes. AKB-9778 activates the Tie2 receptor irrespective of extracellular levels of its binding ligands, angiopoietin-1 (agonist) or angiopoietin-2 (antagonist) and may be the most efficient pharmacologic approach to maintain normal Tie2 activation.

The trial is a randomized, double-masked study designed to assess increasing concentrations of AKB-9778 dosed topically as eye drops. The primary outcome of the study is ocular safety and tolerability with change in IOP) at day 7 as a pharmacodynamic outcome. Conjunctival hyperemia and IOP were assessed at 0 (pre-dose), 2, 4, and 8 hours post-dose on day -1 (baseline), day 1 (first day of AKB-9778 dosing) and day 7 (last day of AKB-9778 dosing).

Based on favorable tolerability and pharmacodynamic findings in cohorts 1-4, Aerpio elected to recruit a fifth cohort of subjects with OHT/POAG on standard of care prostaglandin therapy to assess the safety, tolerability and pilot efficacy of once-daily AKB-9778 (40 mg/mL) as an adjunctive therapy. In the fifth cohort 43 patients were recruited with OHT/POAG and baseline IOP measurements between 17 and 27 mmHg while treated with once-daily prostaglandin therapy. Patients were randomized 3:1 to receive either AKB-9778 (32 subjects) or placebo (11 subjects), administered in the morning for 7 days, while continuing their evening prostaglandin therapy.

Subjects in cohort 5 randomized to the active arm exhibited statistically significant decreases in IOP at all post-AKB-9778 administration timepoints on both days 1 and 7 compared with day -1 baseline values when they were being treated with prostaglandin alone.

Topical ocular administration of AKB-9778 was well tolerated over 7 days in cohort 5. In the active arm treated with AKB-9778 plus prostaglandin, 18.8% of subjects experienced hyperemia compared with 9.1% of subjects in the prostaglandin-alone arm. In all cases, this hyperemia was minimal-to-mild in severity, transient in duration and generally considered non-adverse. There were no reports of conjunctival hemorrhage or pain on instillation during the 7 days of dosing.