Aerpio Pharmaceuticals announced topline results from the company’s 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).
Administration of AKB-9778 twice daily did not meet the study’s primary endpoint of the percentage of patients with an improvement of two or more steps in the study eye diabetic retinopathy severity score (DRSS) compared to placebo. The percentage of patients achieving this endpoint for AKB-9779 twice daily (BID) and placebo were 9.6% and 3.8%, respectively (P=0.270). 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 (P=0.158). The rates of progression to sight-threatening complications, including diabetic macular edema (DME) and/or proliferative diabetic retinopathy (PDR), during the 48-week treatment period were similar between treatment groups.
AKB-9778 did show encouraging data in a number of prespecified, key secondary endpoints, consistent with the observations in the prior phase 2a (TIME-2) trial, including changes in Urine Albumin-Creatinine Ratio (UACR), a measure of kidney function, and in IOP. 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.
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 of 10.9% versus 7.0% in the placebo arm, and headache of 10.9% compared to placebo of 3.5%. There was one death in the study, and it was in the placebo group.
“While we are disappointed in the primary endpoint results of this study, we are nevertheless encouraged by the fact that several other promising findings observed in our prior 3-month phase 2a trial have been prospectively confirmed in this 1-year trial,” Stephen Hoffman, MD, PhD, Chief Executive Officer of Aerpio, said in a company news release. “We and our clinical advisors believe that collectively these data support a potentially important role of the Tie2 pathway for the treatment of diabetic complications, as well as for open angle glaucoma. After a full analysis of the study data, we plan to provide an update on the status of the NPDR program. We would like to thank the patients and investigators that participated in this trial.”
TIME-2b Study Design
The TIME-2b study was a double-masked, placebo-controlled, multicenter trial designed to evaluate the effect of AKB-9778 in patients with moderate-to-severe NPDR. 167 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 TIME-2b study was the percentage of patients who improved by two or more steps in DRSS in the study eye. One of the study’s secondary objectives, the urine albumin to creatinine ratio or UACR, was prospectively included based on a post-hoc analysis of this biomarker in the TIME-2 Phase 2a clinical trial of AKB-9778 in diabetic macular edema.