Aerpio Pharmaceuticals announced new results from the fifth cohort of subjects from a phase 1b trial of a topical ocular formulation of AKB-9778 providing evidence of tolerability and IOP reduction from patients in that cohort with ocular hypertension (OHT) or primary open angle glaucoma (POAG).
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, 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 (see above).
Results from cohort 5 are as follows:
- Subjects in cohort 5 randomized to the active arm exhibited statistically significant decreases in IOP at all post-AKB-9778 administration time points on both Days 1 and 7 compared with Day -1 baseline values when they were being treated with prostaglandin alone (see Figure 1; Diurnal = mean IOP of 2, 4 and 8 hour time points; ** P < 0.05, *** P < 0.001).
- When the change is placebo-corrected, AKB-9778 plus prostaglandin versus prostaglandin alone produced a statistically significant decrease in IOP on Day 7 at 0, 4 and 8 hours post dose as compared to placebo (placebo-adjusted data at 0 hrs. -2.26 mmHg, p = 0.007; 2 hrs. -1.24, p = 0.138; 4 hrs. -1.47 mmHg; p = 0.048; 8 hrs. -1.80 mmHg; p = 0.041). We believe these results suggest a persistent IOP-lowering activity from adding AKB-9778 to standard-of-care prostaglandin therapy.
Topical ocular administration of AKB-9778 was well tolerated over seven 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 seven days of dosing.
“These early data suggest potential for a best in class profile for AKB-9778 to lower IOP when used in combination with prostaglandins,” Brian Levy, DO, M.Sc., CEO of at Ocunexus Therapeutics and former CMO of Aerie Pharmaceuticals, said in a company news release. “Although this is a small study, we observed IOP reductions in the fifth cohort of this trial that are comparable to or better than those produced by common commercial adjunctive therapies used in conjunction with prostaglandins. Moreover, AKB-9778 was well-tolerated through seven days of dosing with minimal hyperemia, no conjunctival hemorrhage and no discomfort on instillation. I look forward to the potential confirmation of these results in a larger and longer duration study.”
Pravin U. Dugel, MD, Partner, Retinal Consultants of Arizona, Clinical Professor, Roski Eye Institute, USC Keck School of Medicine, and Member of Aerpio’s Board of Directors said, “The opportunity to treat glaucoma via a novel mechanism-of-action that targets the Schlemm’s canal and the primary outflow channel may provide great benefit for patients beyond current therapies and definitely warrants further study. In addition to an impressive IOP-lowering activity on top of a prostaglandin, the encouraging tolerability profile observed from this cohort is also important for patient acceptance and compliance, as most current therapies have tolerability issues.”
Based on these results, Aerpio plans to further advance its glaucoma program through strategic alternatives such as a partnership or collaboration.