Regulatory considerations in the development of high-density lipoprotein therapies.

The development of high-density lipoprotein (HDL) therapies has experienced a recent setback with the notable termination of clinical development of torcetrapib, a cholesteryl ester transfer protein inhibitor. Potentially because of off-target actions of torcetrapib, surrogate biomarkers intended to elucidate the impact of the drug on atherosclerosis provided an uninterpretable picture of actual effects. This experience has regulatory implications for HDL-raising therapeutics. Future programs will likely be required to provide preapproval hard evidence of effects on the natural history of disease.