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)

Autor: John C. Davis, Kun Peng, Thomas Gelzleichter, Laura Pascasio Harris, Alexandr Vilimovskij, Whittemore G. Tingley, Robert Kahn, Sofia Mosesova, Kyra J. Cowan, John D. Davis, Nageshwar Budha, Amos Baruch, Josh Lehrer
Rok vydání: 2016
Předmět:
Adult
Male
medicine.medical_specialty
Magnetic Resonance Spectroscopy
Apolipoprotein B
Adolescent
Injections
Subcutaneous
Coronary Disease
030204 cardiovascular system & hematology
Placebo
Antibodies
Monoclonal
Humanized
03 medical and health sciences
chemistry.chemical_compound
Young Adult
0302 clinical medicine
Double-Blind Method
Risk Factors
Internal medicine
medicine
Humans
030212 general & internal medicine
Aged
Aged
80 and over
Inflammation
biology
Dose-Response Relationship
Drug
business.industry
Cholesterol
PCSK9
Antibodies
Monoclonal
Cholesterol
LDL
Middle Aged
Dose–response relationship
Endocrinology
chemistry
Monoclonal
biology.protein
Cytokines
lipids (amino acids
peptides
and proteins)
Female
Antibody
Proprotein Convertase 9
Cardiology and Cardiovascular Medicine
business
Biomarkers
Lipoprotein
Zdroj: The American journal of cardiology. 119(10)
ISSN: 1879-1913
Popis: 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.
Databáze: OpenAIRE
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