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J Am Coll Cardiol. 2014 Jun 17;63(23):2531-40. doi: 10.1016/j.jacc.2014.03.018. Epub 2014 Mar 29.

Anti-PCSK9 monotherapy for hypercholesterolemia: the MENDEL-2 randomized, controlled phase III clinical trial of evolocumab.

Author information

  • 1Jacksonville Center for Clinical Research, Jacksonville, Florida. Electronic address: mkoren@encoredocs.com.
  • 2Center for Clinical and Basic Research, Ballerup, Denmark.
  • 3Bethesda Health Research Center, Bethesda, Maryland.
  • 4Orange County Research Center, Tustin, California.
  • 5Amgen Inc., Thousand Oaks, California.
  • 6L-MARC Research Center, Louisville, Kentucky.

Abstract

OBJECTIVES:

The aim of this study was to compare biweekly and monthly evolocumab with placebo and oral ezetimibe in patients with hypercholesterolemia in a phase III trial.

BACKGROUND:

Evolocumab, a fully human monoclonal antibody against proprotein convertase subtilisin/kexin type 9 (PCSK9), significantly reduced LDL-C in phase II trials.

METHODS:

Patients 18 to 80 years of age with fasting low-density lipoprotein cholesterol (LDL-C) ≥100 and <190 mg/dl and Framingham risk scores ≤10% were randomized (1:1:1:1:2:2) to oral placebo and subcutaneous (SC) placebo biweekly; oral placebo and SC placebo monthly; ezetimibe and SC placebo biweekly; ezetimibe and SC placebo monthly; oral placebo and evolocumab 140 mg biweekly; or oral placebo and evolocumab 420 mg monthly.

RESULTS:

A total of 614 patients were randomized and administered doses. Evolocumab treatment reduced LDL-C from baseline, on average, by 55% to 57% more than placebo and 38% to 40% more than ezetimibe (p < 0.001 for all comparisons). Evolocumab treatment also favorably altered other lipoprotein levels. Treatment-emergent adverse events (AEs), muscle-related AEs, and laboratory abnormalities were comparable across treatment groups.

CONCLUSIONS:

In the largest monotherapy trial using a PCSK9 inhibitor to date, evolocumab yielded significant LDL-C reductions compared with placebo or ezetimibe and was well tolerated in patients with hypercholesterolemia. (Monoclonal Antibody Against PCSK9 to Reduce Elevated LDL-C in Subjects Currently Not Receiving Drug Therapy for Easing Lipid Levels-2 [MENDEL-2]; NCT01763827).

Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

KEYWORDS:

PCSK9 inhibition; dyslipidemia; evolocumab; monotherapy

PMID:
24691094
[PubMed - indexed for MEDLINE]
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