Aerpio Pharmaceuticals announced interim results from its phase 1b clinical trial of a topical ocular formulation of AKB-9778 in development as a potential treatment for primary open angle glaucoma (POAG).
The phase 1b study is an ongoing randomized, double-masked study designed to assess increasing concentrations of AKB-9778 dosed topically as eye drops (5mg/ml QD, 15 mg/ml QD, 40 mg/ml QD and 40 mg/ml BID) in 4 sequential cohorts of 12 subjects, randomized 3:1 to receive AKB-9778 or placebo, for 7 days. The primary outcome of the study is ocular safety and tolerability with change in IOP as a pharmacodynamic outcome. Conjunctival hyperemia grade and IOP were assessed prior to dosing and at 2-, 4- and 8-hours post-dose on Day 1 and Day 7. The unmasked interim analysis was limited to the first three cohorts (5 mg/ml QD, 15 mg/ml QD, 40 mg/ml QD). Topical ocular administration of AKB-9778 was well tolerated over 7 days at all dose levels for the first three cohorts. Compared to placebo, there was a dose dependent increase in minimal to mild conjunctival hyperemia with AKB-9778, which was transient and generally considered non-adverse. There was also a time and dose dependent reduction in IOP that, in the highest QD dose cohort peaked at 4 hours post-dose (-1.47 mmHg; p = 0.041)/-10.64%; p = 0.027) and was sustained through eight hours on day 7, returning to baseline levels at 24 hours post-dose. Based on these interim results, the phase 1b protocol has been amended to include patients with ocular hypertension and POAG to further assess safety and activity on IOP in the target patient population. The company expects to announce full results of the ongoing phase 1b study in the first quarter of 2020.
“We are encouraged by the early safety findings and potential efficacy signal of this ongoing Phase 1b trial,” Kevin Peters, MD, Chief Scientific Officer of Aerpio Pharmaceuticals, said in the news release. “The conventional outflow tract is responsible for the majority of fluid drainage from the front of the eye, which is critical for maintaining normal IOP and is often the site of pathology implicated in the increased IOP in patients suffering from POAG. Recent mouse and human genetic data establish a key role for the Tie2 pathway in the development and maintenance of Schlemm’s canal, a key component of the conventional outflow tract. AKB-9778, a potent small molecule Tie2 activator, has shown IOP lowering effects after subcutaneous administration in two sequential phase 2 studies in patients with diabetic retinopathy and normal IOP. We now look forward further to evaluating AKB-9778’s safety and activity on IOP in patients with ocular hypertension and POAG.”