Drug release profile of a novel exenatide long-term drug delivery system (OKV-119) administered to cats

Abstract

Beneficial weight-loss properties of glucagon-like peptide-1 receptor agonists (GLP-1RA) in obese people, with corresponding improvements in cardiometabolic risk factors, are well established. OKV-119 is an investigational drug delivery system that is being developed for the long-term delivery of the GLP-1RA exenatide to feline patients. The purpose of this study was to evaluate the drug release characteristics of subcutaneous OKV-119 implants configured to release exenatide for 84 days. Following a 7-day acclimation period, five purpose-bred cats were implanted with OKV-119 protypes and observed for a 112-day study period. Food intake, weekly plasma exenatide concentrations and body weight were measured. Exenatide plasma concentrations were detected at the first measured timepoint (Day 7) and maintained above baseline for over 84 Days. Over the first 28 days, reduced caloric intake and a reduction in body weight were observed in four of five cats. In these cats, a body weight reduction of at least 5% was maintained throughout the 112-day study period. This study demonstrates that a single OKV-119 implant can deliver the GLP-1RA exenatide for a months long duration. Results suggest that exposure to exenatide plasma concentrations ranging from 1.5 ng/ml to 4 ng/ml are sufficient for inducing weight loss in cats.

Keywords: Adherence; Drug delivery; Exenatide; Feline diabetes; Feline obesity.

Fig. 1

Exenatide plasma concentrations from baseline to Day 105 in purpose bred cats implanted with OKV-119 protypes configured to release exenatide for 84 Days

Fig. 2

Heat map of food consumed by cats (n = 5) during the acclimation period (Days − 6 to Day − 1) and after insertion of the OKV-119 implant (Day 0 to Day 28). Each box represents the amount of food remaining (right y-axis) on a given day with study days (left y-axis). Columns correspond to each cat on the x-axis. Darker shades indicate less food consumed on a given day. Caloric intake was not reported on Days 0, 7, 14 and 28 (crossed-out boxes) because food was removed on the eve prior fasting blood draws

Fig. 3

Percent change in body weight in five purpose bred cats from Day 0 to Day 112 following administration of a subcutaneous OKV-119 implant. Cats were housed in individual pens for the intitial 28 day study period, and then housed as a group for the remainder of the study period