While some companies are pursuing compounds that affect energy metabolism through centrally mediated pathways, Karo Bio AB and partner Bristol-Myers Squibb Co. are bypassing the central nervous system wiring with their selective thyroid hormone nuclear receptor agonists that turn on expression of genes related to metabolism.

Leptin, a hormone that acts on the hypothalamus to affect both hunger and cellular metabolism, is in development to treat obesity by Amgen Inc. (AMGN, Thousand Oaks, Calif.), while Regeneron Pharmaceuticals Inc. (REGN, Tarrytown, N.Y.) is testing its Axokine CNTF, which is related to leptin, in Phase III trials.