Atorvastatin with or without an Antibody to PCSK9 in Primary Hypercholesterolemia

Authors

Eli M. Roth, Sterling Res Grp
James M. McKenny, Virginia Commonwealth University
Corinne Hanotin, Sanofi
Gaelle Asset, Sanofi
Evan A. Stein, Metab & Atherosclerosis Res Ctr, Medpace Reference Labs

Document Type

Article

Original Publication Date

2012

Journal/Book/Conference Title

The New England Journal of Medicine

Volume

367

DOI of Original Publication

10.1056/NEJMoa1201832

Comments

Originally Published at :http://dx.doi.org/10.1056/NEJMoa1201832

Date of Submission

January 2015

Abstract

Background

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.

Methods

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.

Results

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

Conclusions

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.)

Rights

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