Target engagement markers to take the right drug to the market – liver glycogen case

Target engagement confirmation was of interest for a global pharmaceutical company developing a dual GLP-1/glucagon agonist. In the absence of a suitable target engagement marker, its physiological response marker could be used as a substitute

 

Liver glycogen as a marker of glucagon signalling

 

It is well-known that glucagon promotes glycogen conversion to glucose (glycogenolysis) in the liver. We therefore implemented a method using 13C magnetic resonance spectroscopy (MRS) to assess liver glycogen content without using invasive biopsies. The study successfully showed a significant reduction in liver glycogen after treatment compared to controls, thus serving as a marker of glucagon receptor signalling and the pharmacodynamic effects of the dual agonist.

 

 

Antaros Medical News

Antaros┬áMedical – Publications

 

“This is a strong marker of glucagon receptor signalling and of pharmacodynamic effects.”

 

Edvin Johansson

Senior Director MR Imaging & Modelling

The importance of identifying target engagement in type 2 diabetes

Type 2 diabetes affects over 400 million people worldwide (WHO 2019). Although significant advances have been made in diabetes medicine there remains substantial unmet medical need. For new candidate drugs, it is necessary to have tools to investigate novel mechanisms of actions, efficacy and tissue distribution in order to guide development programme strategies or to differentiate against competition. In addition, complexity is increasing with e.g. dual or trigonal agonists that bind several targets with different but also overlapping biological effects. Therefore, sophisticated solutions are required for studying target engagement in clinical trials.