Aerpio Pharmaceuticals dosing of the first subject in a phase 1b trial of a topical ocular formulation of AKB-9778 in development for treatment of primary open angle glaucoma (POAG).
The phase 1 study is a double-masked, multiple-ascending dose trial and will enroll four cohorts of 12 subjects. Subjects will receive increasing daily doses of a topical ocular formulation of AKB-9778 or placebo for 7 days. The primary endpoint of the trial is ocular safety and tolerability, with IOP lowering as the key pharmacodynamic endpoint.
“POAG is characterized by increased IOP leading to optic nerve and neuroretina anomalies and progressive visual field defects,” Kevin Peters, M.D., Chief Scientific Officer of Aerpio Pharmaceuticals, said in a company news release. “Reducing IOP has proven to be the only clinical approach shown to slow or prevent vision loss. The conventional outflow pathway, consisting of the trabecular meshwork and a specialized vessel called Schlemm’s canal, controls IOP and has been identified as the site of increased resistance to aqueous humor outflow in POAG. We have recently shown in animal models that topical ocular dosing of AKB-9778 lowers IOP via its action on Schlemm’s canal, and in two sequential phase 2 clinical studies, we have shown that subcutaneous administration of AKB-9778 significantly reduced IOP in ocular normotensive patients. Bases on these data, we believe that AKB-9778 could provide a novel and differentiated approach to treating POAG and the first approach that directly affects Schlemm’s canal. We look forward to sharing the results of this study by the end of 2019.”
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.