A regulatory perspective argues the termination of torcetrapib means future HDL therapies will need preapproval proof of effects on actual disease progression (Am J Cardiol 2007)

The development of HDL-raising therapies suffered a notable setback with the termination of clinical development for torcetrapib, a CETP inhibitor. This regulatory perspective argues that surrogate biomarkers intended to reveal the effect of torcetrapib on atherosclerosis instead provided an uninterpretable picture of its actual effects, potentially because of off-target actions of the drug. The author concludes this experience carries regulatory implications for HDL-raising therapeutics broadly, and that future development programs will likely be required to provide hard preapproval evidence of effects on the natural history of disease, rather than relying on surrogate markers alone.