Effects of RG7652, a Monoclonal Antibody Against PCSK9, on LDL-C, LDL-C Subfractions, and Inflammatory Biomarkers in Patients at High Risk of or With Established Coronary Heart Disease (from the Phase 2 EQUATOR Study)

Am J Cardiol. 2017 May 15;119(10):1576-1583. doi: 10.1016/j.amjcard.2017.02.020. Epub 2017 Mar 1.


RG7652 (MPSK3169A), a fully human immunoglobulin G1 (IgG1) monoclonal antibody directed against proprotein convertase subtilisin/kexin type 9 (PCSK9), blocks the interaction between PCSK9 and low-density lipoprotein (LDL) receptor. EQUATOR (ClinicalTrials.govNCT01609140), a randomized, double-blind, and dose-ranging phase 2 study, evaluated RG7652 in patients (1) at high risk for or (2) with coronary heart disease (CHD). The primary end point was change in LDL cholesterol (LDL-C) from baseline to day 169. Patients (n = 248; median age, 64 years; 57% men; 52% with established CHD; 82% on statins) with baseline LDL-C levels of 90 to 250 mg/dl (mean, 126 mg/dl) continuing on standard-of-care therapy were randomized to receive 1 of 5 RG7652 doses or placebo, subcutaneously every 4, 8, or 12 weeks for 24 weeks. Significant dose-dependent reductions in LDL-C levels from baseline to nadir (56 to 74 mg/dl [48% to 60%]) were observed in all RG7652-dosed patients; effects persisted to day 169 with the highest doses (reduction vs placebo up to 62 mg/dl [51%]) with no unexpected safety signals. RG7652 reduced apolipoprotein B and lipoprotein(a) levels. LDL-C subfraction analysis by nuclear magnetic resonance spectroscopy revealed a prominent decrease in large LDL-C and some decrease in small LDL particles. There was significant reduction in mean particle size of LDL-C on day 169 but no significant reductions in systemic markers of inflammation (high-sensitivity C-reactive protein, interleukin-6, and tumor necrosis factor-alpha). RG7652 reduced LDL-C levels and was well tolerated in patients at high risk for or with CHD on standard-of-care therapy. In conclusion, RG7562 treatment affected large LDL-C and, to a lesser extent, small LDL-C particles; RG7562 did not affect systemic circulating pro-inflammatory cytokines or high-sensitivity C-reactive protein.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal, Humanized
  • Biomarkers / blood
  • Cholesterol, LDL / blood*
  • Cholesterol, LDL / drug effects
  • Coronary Disease / blood
  • Coronary Disease / diagnosis
  • Coronary Disease / prevention & control*
  • Cytokines / blood*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Humans
  • Inflammation / blood
  • Injections, Subcutaneous
  • Magnetic Resonance Spectroscopy
  • Male
  • Middle Aged
  • Proprotein Convertase 9 / immunology*
  • Risk Factors
  • Young Adult


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Biomarkers
  • Cholesterol, LDL
  • Cytokines
  • RG7652
  • PCSK9 protein, human
  • Proprotein Convertase 9

Associated data

  • ClinicalTrials.gov/NCT01609140