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.
Orloff
David G
DG
Medpace, Inc., Cincinnati, Ohio, USA. d.orloff@medpace.com
D000924:Anticholesteremic Agents / Q000494:pharmacology*; D050197:Atherosclerosis / Q000188:drug therapy*; D015415:Biomarkers; D017277:Drug Approval; D006801:Humans; D008075:Lipoproteins, HDL / Q000502:physiology*; D011804:Quinolines / Q000494:pharmacology*
D000924:Anticholesteremic Agents; D015415:Biomarkers; D008075:Lipoproteins, HDL; D011804:Quinolines; C483909:torcetrapib