Abstract 13651: Efficacy and Safety of Alirocumab in Japanese Patients With Hypercholesterolemia on Stable Statin Therapy: First Data With the 75 mg Every Two Weeks Dose
Introduction: The current study (NCT01812707) evaluated the effects of alirocumab, a fully human monoclonal antibody to proprotein convertase subtilisin kexin type 9 (PCSK9), at doses of 50, 75 and 150 mg once every two weeks (Q2W) in Japanese patients with hypercholesterolemia on stable atorvastatin therapy (5-20 mg).
Methods: This multicenter, double-blind, placebo-controlled trial randomized 100 patients with LDL-C ≥100 mg/dL on statin therapy to receive either alirocumab 50, 75 or 150mg Q2W via single 1 mL subcutaneous injection or placebo. The primary efficacy endpoint was % change in calculated LDL-C from baseline to Week 12. Safety was assessed by adverse events (AEs).
Results: Demographics and disease characteristics were consistent among the four groups (25 patients per group); mean baseline LDL-C ranged from 120.5-122.2 mg/dL and 64% of patients were receiving atorvastatin doses of 5 mg, with 36% on doses of 10 or 20 mg.
At Week 12, all alirocumab doses significantly reduced LDL-C from baseline vs placebo (all P<0.0001) in a dose-dependent manner: least-squares mean reductions of 3, 55, 62 and 72% from baseline were observed for placebo, 50, 75, and 150 mg alirocumab Q2W, respectively, corresponding to mean (SD) LDL-C concentrations of 116.0 (16.8), 54.4 (16.3), 46.4 (18.5) and 35.0 (24.1) mg/dL. Total cholesterol, Lp(a) and triglycerides were also substantially reduced with alirocumab.
Treatment emergent AEs (TEAEs) were reported in 8 (32%), 13 (52%), 12 (48%), and 16 (64%) patients in the placebo, alirocumab 50, 75, and 150 mg Q2W groups, respectively. The most frequent TEAE, nasopharyngitis, occurred in 18 patients across the four groups. Eight patients had local injection site reactions of mild intensity with no dose relation. Two patients had serious AEs: vertigo (n=1, placebo) and breast cancer (n=1, 150 mg alirocumab), neither considered related to the study drug.
Conclusions: Alirocumab demonstrated robust efficacy over 12 weeks, reducing LDL-C from baseline by 55-72% when added to stable statin therapy. TEAEs were reported in 49% of patients overall, the most frequent across the groups being nasopharyngitis. This study provided the first data for the alirocumab 75 mg Q2W dose in a Japanese population, reducing LDL-C by 62%.
Author Disclosures: T. Teramoto: Honoraria; Modest; GlaxoSmithKline, Astellas KK, MSD KK, Kissei KK, Kowa KK, Daiichi Sankyo KK, Pfizer KK, Bayer KK, Shionogi KK, Kobayashi KK. Consultant/Advisory Board; Modest; GlaxoSmithKline, Astellas KK, MSD KK, Kissei KK, Kowa KK, Daiichi Sankyo KK, Pfizer KK, Bayer KK, Shionogi KK, Kobayashi KK. M. Kobayashi: Employment; Significant; Sanofi. K. Uno: Employment; Significant; Sanofi. Y. Takagi: Employment; Significant; Sanofi. O. Matsuoka: None. M. Sugimoto: None. S. Inoue: None. F. Minami: None. M.T. Baccara-Dinet: Employment; Significant; Sanofi.
- © 2014 by American Heart Association, Inc.