Document Type


Original Publication Date


Journal/Book/Conference Title

The New England Journal of Medicine



DOI of Original Publication



Originally Published at :

Date of Submission

January 2015



Serum proprotein convertase subtilisin/kexin 9 (PCSK9) binds to low-density lipoprotein (LDL) receptors, increasing the degradation of LDL receptors and reducing the rate at which LDL cholesterol is removed from the circulation. REGN727/SAR236553 (designated here as SAR236553), a fully human PCSK9 monoclonal antibody, increases the recycling of LDL receptors and reduces LDL cholesterol levels.


We performed a phase 2, multicenter, double-blind, placebo-controlled trial involving 92 patients who had LDL cholesterol levels of 100 mg per deciliter (2.6 mmol per liter) or higher after treatment with 10 mg of atorvastatin for at least 7 weeks. Patients were randomly assigned to receive 8 weeks of treatment with 80 mg of atorvastatin daily plus SAR236553 once every 2 weeks, 10 mg of atorvastatin daily plus SAR236553 once every 2 weeks, or 80 mg of atorvastatin daily plus placebo once every 2 weeks and were followed for an additional 8 weeks after treatment.


The least-squares mean (±SE) percent reduction from baseline in LDL cholesterol was 73.2±3.5 with 80 mg of atorvastatin plus SAR236553, as compared with 17.3±3.5 with 80 mg of atorvastatin plus placebo (P


In a randomized trial involving patients with primary hypercholesterolemia, adding SAR236553 to either 10 mg of atorvastatin or 80 mg of atorvastatin resulted in a significantly greater reduction in LDL cholesterol than that attained with 80 mg of atorvastatin alone. (Funded by Sanofi and Regeneron Pharmaceuticals; ClinicalTrials. gov number, NCT01288469.)


From The New England Journal of Medicine, Roth, E. M., McKenny, J. M., Hanotin, C. et al., Atorvastatin with or without an Antibody to PCSK9 in Primary Hypercholesterolemia, Vol. 367, Page 1891, Copyright © 2012 Massachusetts Medical Society. Reprinted with permission.

Is Part Of

VCU Pharmacotherapy and Outcomes Science Publications

nejmoa1201832_appendix.pdf (474 kB)
Supplementary Appendix

nejmoa1201832_disclosures.pdf (236 kB)
Disclosure Forms

nejmoa1201832_protocol.pdf (1886 kB)