Aerpio Therapeutics announced top-line results from the TIME-2b study, a Phase 2b clinical trial designed to assess the efficacy and safety of Aerpio’s lead candidate, AKB-9778, for patients with moderate to severe non-proliferative diabetic retinopathy (NPDR).
TIME-2b was a double-masked, placebo-controlled, multi-center trial designed to evaluate the effect of AKB-9778 in 167 patients with moderate-to-severe NPDR. The patients were randomized to receive 48 weeks of treatment with either AKB-9778 15 mg subcutaneously once daily (and placebo subcutaneously once daily), AKB-9778 15 mg subcutaneously twice daily, or placebo subcutaneously twice daily. The primary endpoint of the study was the percentage of patients who improved by two or more steps in diabetic retinopathy severity score (DRSS) in the study eye. AKB-9778 twice daily did not meet the study’s primary endpoint compared to placebo. The percentage of patients achieving this endpoint for AKB-9778 twice daily (BID) and placebo were 9.6% and 3.8%, respectively. In all qualified eyes (i.e., study eyes and fellow eyes that met the inclusion/exclusion criteria), the percentage of eyes achieving this endpoint was 8.6% and 2.7%, for AKB-9778 BID and placebo, respectively. AKB-9778 was found to be safe and well-tolerated in this patient population through 48 weeks of twice-daily dosing. The most common adverse events with higher incidence in the AKB-9778 BID group were dizziness and headache.
The company plans to advance a topical drop formulation of AKB-9778 into clinical development and expects to initiate a Phase 1b study in the second quarter of 2019 with results anticipated by the end of 2019.
About non-proliferative diabetic retinopathy
Non-proliferative diabetic retinopathy occurs in a large majority of diabetic patients (both type I and type II). Non-proliferative diabetic retinopathy is characterized by microaneurisms within the retina and small areas of hemorrhaging (bleeding) within the retina. Since the blood vessels have been damaged from high blood sugar levels, fluid can leak into the retina, causing edema and swelling of the retina.
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.