Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptor superfamily comprising four subtypes designated PPAR alpha, PPAR gamma1, PPAR gamma2, and PPAR delta. PPARs regulate gene expression, thereby controlling energy metabolism. PPAR gamma has a key role in adipogenesis, insulin sensitivity, and glucose and lipid metabolism, and also plays a major role in vascular biology. Thiazolidinediones (TZDs) are the ligands of PPAR gamma. Rosiglitazone and pioglitazone are established and economically successful PPAR gamma agonists with combined 2007 sales of about US$ 6.6 bln explaining the high interest in next generation products. The thiazolidinedione's (TZDs) recently found themselves in the spotlight when the safety of GlaxoSmithKline's rosiglitazone was brought into question by a meta-analysis that associated it with increased risk of myocardial ischemic events. This means that physicians and the FDA may require new drugs to stand the test of time before they recommend or initiate them as first- or second-line therapy. As a consequence, sales of GSK’s rosiglitzone declined by more than 20 %, but for the benefit of Takeda’s pioglitzone which raised by 23 %. A number of next generation PPAR gamma agonists are in clinical development, some of them including PPAR alpha agonistic action in a balanced manner. The PPAR alpha agonist fenofibrate from Solvay Pharmaceuticals and Abbott yielded 2007 sales of US$ 1.9 bln. Next generation products are in advanced development to stop generic erosion of branded product sales.

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