Arena Pharmaceuticals Announces First In Class Treatment for Type 2 Diabetes Begins Phase 1 Trial

Phase 1 clinical trial of APD597, a novel first in class oral drug candidate that targets the glucose-dependent insulinotropic receptor (GDIR) for the treatment of type 2 diabetes will begin shortly. The GDIR has the potential to stimulate insulin release in response to increases in blood glucose. Ortho-McNeil-Janssen Pharmaceuticals will be a partner in the program.

Ortho-McNeil’s Phase 1 program will evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of APD597 in single and multiple ascending dose studies in healthy volunteers. The planned clinical studies will also include the evaluation of patients with type 2 diabetes.

The GDIR is an orphan G protein-coupled receptor (GPCR), and it is expressed in beta cells, the cells in the pancreas responsible for producing insulin in response to increases in blood glucose. The GDIR signals through a similar intracellular pathway as the GLP-1 receptor, with common downstream effects, but unlike the GLP-1 receptor, the GDIR has proven amenable to small molecule drug discovery.

Stimulation of the GDIR is intended to more efficiently promote insulin release by beta cells in response to elevated blood glucose levels. In addition, the GDIR is expressed in cells other than pancreatic beta cells, such as endocrine cells in the gastrointestinal tract, and in preclinical studies the GDIR stimulates the release of GLP and GIP, two incretins that play an important role in insulin regulation and glucose homeostasis. GDIR stimulation has also been found to increase the levels and activity of intracellular factors thought to be involved in the preservation of beta cells, and GDIR signaling may therefore also serve to maintain beta cell mass in type 2 diabetes.