CETP Inhibition and HDL: Joint Statement by IAS, EAS and NLA
Joint Statement by EAS, IAS and NLA on CETP Inhibition and HDL
News - May 21, 2012May 21, 2012
The IAS, EAS and NLA released on May 21, 2012 a joint statement about the recent termination of the development of dalcetrapib, a cholesteryl ester transfer protein (CETP) inhibitor, by Hoffman-La Roche (Genentech) after its Phase III dal-OUTCOMES trial in acute coronary syndrome patients failed to demonstrate a significant reduction in cardiovascular adverse events[1]. In contrast to the earlier CETP inhibitor, torcetrapib, no safety concerns were reported.
While disappointing, the pursuit of an extensive programme of clinical trials and basic research to develop dalcetrapib has provided new information on the biology of HDL in both man and animal models, and on CETP inhibition as a viable therapeutic target for raising levels of HDL-cholesterol. Several other CETP inhibitors that raise HDL-cholesterol levels to a greater extent than dalcetrapib and also significantly lower LDL cholesterol and novel HDL-raising agents remain under development by both major pharmaceutical manufacturers and biotechnology companies. We anticipate that these ongoing research efforts will shed further light on the feasibility of acute and/or chronic HDL modification as approaches to improve cardiovascular outcomes in dyslipidemic patients with cardiometabolic disease.
The National Cholesterol Education Program in the United States[2] and the 2011 European Society of Cardiology/EAS Guidelines for the Management of Dyslipidaemias[3] emphasize that low levels of HDL-cholesterol represent a strong and independent risk factor for the development of premature atherosclerosis and cardiovascular disease; and the measurement of HDL-cholesterol should be used in predicting risk and choosing goals for reduction of LDL and non-HDL cholesterol. Further research may provide a means of changing HDL cholesterol with a beneficial effect on the incidence of cardiovascular disease.
The IAS, EAS and NLA released on May 21, 2012 a joint statement about the recent termination of the development of dalcetrapib, a cholesteryl ester transfer protein (CETP) inhibitor, by Hoffman-La Roche (Genentech) after its Phase III dal-OUTCOMES trial in acute coronary syndrome patients failed to demonstrate a significant reduction in cardiovascular adverse events[1]. In contrast to the earlier CETP inhibitor, torcetrapib, no safety concerns were reported.
While disappointing, the pursuit of an extensive programme of clinical trials and basic research to develop dalcetrapib has provided new information on the biology of HDL in both man and animal models, and on CETP inhibition as a viable therapeutic target for raising levels of HDL-cholesterol. Several other CETP inhibitors that raise HDL-cholesterol levels to a greater extent than dalcetrapib and also significantly lower LDL cholesterol and novel HDL-raising agents remain under development by both major pharmaceutical manufacturers and biotechnology companies. We anticipate that these ongoing research efforts will shed further light on the feasibility of acute and/or chronic HDL modification as approaches to improve cardiovascular outcomes in dyslipidemic patients with cardiometabolic disease.
The National Cholesterol Education Program in the United States[2] and the 2011 European Society of Cardiology/EAS Guidelines for the Management of Dyslipidaemias[3] emphasize that low levels of HDL-cholesterol represent a strong and independent risk factor for the development of premature atherosclerosis and cardiovascular disease; and the measurement of HDL-cholesterol should be used in predicting risk and choosing goals for reduction of LDL and non-HDL cholesterol. Further research may provide a means of changing HDL cholesterol with a beneficial effect on the incidence of cardiovascular disease.
References
- "Roche provides update on Phase III study of dalcetrapib." Roche press release, May 7, 2012; http://www.roche.com/media/media_releases/med-cor-2012-05-07.htm.
- ATP III Update 2004: Implications of Recent Clinical Trials for the ATP III Guidelines. JAMA, 2001;285:2486-2497
- ESC/EAS Guidelines for the management of dyslipidaemias. June 2011 Atherosclerosis. 2011 Jul; 217(1):3-46.
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