AKB-9778, a small molecule competitive inhibitor of vascular endothelial-protein tyrosine phosphatase (VE-PTP), has a good safety and efficacy profile in patients with diabetic macular oedema, suggests a preliminary dose-escalation study.
By blocking VE-PTP, AKB-9778 promotes the activation of Tie2, a protein involved in the regulation of vascular permeability, explain the researchers. In preclinical studies, AKB-9778 has been shown to suppress vascular leakage as well as neovascularisation of the retina and choroid, they add.
In this phase Ib trial, four groups of six patients were treated with open-label AKB-9778 self-administered twice daily via subcutaneous injections at doses of 5.0 mg, 15.0 mg, 22.5 mg or 30.0 mg for 4 weeks.
Participants treated with the higher 22.5 mg and 30.0 mg doses, but not those given the 5.0 mg and 15.0 mg doses, experienced headache, dizziness and vasovagal events such as presyncope or syncope – adverse events that are consistent with the anticipated vasodilatory activity of AKB-9778, say the researchers.
“Modest decreases” in resting systolic blood pressure were also observed in the 22.5 mg and 30.0 mg groups, they report, adding that these effects and the adverse events were “transient” and “generally resolved” shortly after dosing.
At 4 weeks, best-corrected visual acuity (BCVA) improved from intake in the 15.0 mg, 22.5 mg and 30.0 mg groups; of 18 participants, 10 achieved an improvement of five to 10 letters, one improved by 11 letters and two by over 15 letters.
Moreover, seven patients who received AKB-9778 at doses of 15.0 mg or more showed decreases in study eye central subfield thickness (CST) from baseline, with reductions of over 100 μm in five patients and of 50 to 100 μm in two patients.