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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
JACC - Journal of the American College of Cardiology, 06/25/2012
Clinical Article
McKenney JM et al. – When added to atorvastatin, PCSK9 inhibition with SAR236553 further reduces LDL–C by 40% to 72%. These additional reductions are both dose– and dosing frequency–dependent.
Methods- This double–blind, parallel–group, placebo–controlled trial.
- Randomized 183 patients with LDL–C 100 mg/dl (2.59 mmol/l) on stable–dose atorvastatin 10, 20, or 40 mg for ≥ 6 weeks to: subcutaneous placebo every 2 weeks (Q2W); SAR236553 50, 100, or 150 mg Q2W; or SAR236553 200 or 300 mg every 4 weeks (Q4W), alternating with placebo for a total treatment period of 12 weeks.
- SAR236553 demonstrated a clear dose–response relationship with respect to percentage LDL–C lowering for both Q2W and Q4W administration: 40%, 64%, and 72% with 50, 100, and 150 mg Q2W, respectively, and 43% and 48% with 200 and 300 mg Q4W.
- LDL–C reduction with placebo at week 12 was 5%.
- SAR236553 also substantially reduced non–high–density lipoprotein cholesterol, apolipoprotein B, and lipoprotein(a).
- SAR236553 was generally well tolerated.
- One patient on SAR236553 experienced a serious adverse event of leukocytoclastic vasculitis.