Aerpio Pharmaceuticals announced that Kevin Peters, MD, Aerpio’s Chief Scientific Officer, presented data from the fifth cohort of subjects from a phase 1b trial showing the potential of a topical ocular formulation of AKB-9778, a VE-PTP inhibitor and Tie2 activator, to lower IOP with minimal conjunctival hyperemia when combined with standard-of-care prostaglandin therapy. The data were presented at the Glaucoma 360 New Horizons Forum 2020, on February 7, in San Francisco.
The presentation included an updated dataset from a phase 1b trial of a topical ocular formulation of AKB-9778 from the fifth cohort of patients with ocular hypertension (OHT) or primary open angle glaucoma (POAG). The updated results from the fifth cohort will be posted on the company’s website.
“We continue to be encouraged by the findings from Aerpio’s topical ocular formulation of AKB-9778 in patients with ocular hypertension or primary open angle glaucoma,” Brian Levy, DO, M.Sc., CEO of at Ocunexus Therapeutics and former CMO of Aerie Pharmaceuticals, said in a company news release. “The IOP lowering observed when AKB-9778 was combined with a prostaglandin in the fifth cohort of Aerpio’s phase 1b trial was comparable to or better than those produced by common commercial adjunctive therapies. Importantly, AKB-9778 achieved this IOP lowering while causing minimal conjunctival hyperemia, no conjunctival hemorrhage, and no discomfort on instillation. Additionally, AKB-9778’s novel mechanism of action that targets the Schlemm’s canal increases our excitement for this program and the results we’ve seen to-date.”
The phase 1b 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). Results from the first 3 cohorts, each comprising 12 subjects with normotensive eyes (non-glaucoma subjects), were reported on October 10, 2019. Subsequently, results from cohort 4, also containing 12 subjects with normotensive eyes, were observed to be consistent with those from cohorts 1 through 3.
Based on favorable tolerability and pharmacodynamic findings in these ocular normotensive subjects from the first four cohorts, 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. Conjunctival hyperemia and IOP were assessed in the same manner as described for cohorts 1-4.
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.