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|Objective:||To compare the effect of SAR236553 (REGN727) with placebo on the occurrence of cardiovascular (CV) events in patients who have experienced a recent ACS event and are receiving evidence-based medical and dietary management of dyslipidemia|
|Study design:||Multicentre, randomized, double-blind, placebo-controlled, parallel group Phase III study|
~18,000 patients aged at least 40 years who have experienced an ACS event 4 to 16 weeks before randomization, and with low-density lipoprotein cholesterol (LDL-C) ³70 mg/dL (1.8 mmol/L)
|Primary outcome:||CV events, a composite endpoint of coronary heart disease (CHD) death, non-fatal myocardial infarction (MI), fatal and non-fatal ischemic stroke and unstable angina requiring hospitalization|
|Other efficacy variables:||
|Safety variables:||Adverse events and clinical laboratory investigations|
Eligible patients will be randomised (1:1) to treatment with SAR236553/(REGN727) 75 mg every 2 weeks or matching placebo, given as a 1 mL subcutaneous injection, in addition to their background optimised lipid modifying therapy. If patients do not reach a pre-determined LDL-C goal with the initial treatment they will be uptitrated to a dose of 150 mg or matching placebo every 2 weeks.The planned duration of follow-up is 5 years and the anticipated date of study closure is Quarter 1, 2018.
Recent trials provide a rationale for monoclonal antibody therapy targeting PCSK9, as an adjuvant therapy in statin-treated patients. Not only does this treatment reduce LDL-C levels by more than 60% on top of statin therapy, but there are also beneficial effects on atherogenic dyslipidemia. Specifically, treatment with SAR236553 (REGN727) 150 mg every 2 weeks lowered triglycerides by ~19% and raised high-density lipoprotein cholesterol (HDL-C) by 5.5%, in addition to also lowering lipoprotein(a) by ~29%1 These data suggest that SAR236553 (REGN727) may have potential benefit in reducing a substantial burden of lipid-related residual vascular risk.
On the basis of these promising data, investigation of SAR236553 (REGN727) has been expanded in the ODYSSEY Phase III clinical programme, with anticipated enrolment of more than 22,000 patients in 11 clinical trials designed to investigate the long-term efficacy and safety of this agent as monotherapy and in combination with other lipid-modifying therapy.
ODYSSEY OUTCOMES is the most important trial as it will evaluate the effect on CV outcomes of SAR236553 (REGN727) on top of statin therapy in a high-risk ACS population. However, we will have to wait some time, as results from ODYSSEY OUTCOMES trial are not expected until 2018.
1. McKenney JM, Koren MJ, Kereiakes DJ, Hanotin C, Ferrand AC, Stein EA. Safety and efficacy of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 serine protease, SAR236553/REGN727, in patients with primary hypercholesterolemia receiving ongoing stable atorvastatin therapy. J Am Coll Cardiol 2012;59:2344-53.
|Key words||PCSK9; SAR236553/REGN727; triglycerides; residual cardiovascular risk; ODYSSEY OUTCOMES|