Efficacy and Safety of Alirocumab in Japanese Subjects (Phase 1 and 2 Studies)

• Published in: The American journal of cardiology Vol. 118; no. 1; pp. 56 - 63
• Main Authors: Teramoto, Tamio, Kobayashi, Masahiko, Uno, Kiyoko, Takagi, Yoshiharu, Matsuoka, Osamu, Sugimoto, Masayuki, Inoue, Satoshi, Minami, Fumiko, Baccara-Dinet, Marie Thérèse
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2016; Elsevier Limited
• Subjects: Adult; Aged; Antibodies, Monoclonal - therapeutic use; Apolipoproteins; Atherosclerosis; Cardiovascular; Cardiovascular disease; Cholesterol; Cholesterol, LDL - blood; Coronary vessels; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug dosages; Female; Humans; Hypercholesterolemia - drug therapy; Japan; Laboratories; Lipids; Low density lipoprotein; Male; Middle Aged; Mortality; Studies; Treatment Outcome; Young Adult; coronary artery disease; PCSK9; statin; lipid-lowering drugs; Atherosclerosis; monoclonal antibodies
• ISSN: 0002-9149; 1879-1913
• DOI: 10.1016/j.amjcard.2016.04.011

We assessed the safety and tolerability of ascending single doses of alirocumab in healthy Japanese subjects and evaluated the effect of alirocumab at 3 doses (50, 75, 150 mg) on low-density lipoprotein cholesterol (LDL-C) reduction in patients with primary hypercholesterolemia on atorvastatin. A randomized, single ascending-dose study of alirocumab (100, 150, 250, or 300 mg) or placebo (3:1 ratio), administered subcutaneously, was conducted in 32 healthy Japanese men. The phase 2, randomized, double-blind, placebo-controlled, parallel-group study was performed in patients with primary hypercholesterolemia (defined as calculated LDL-C ≥100 mg/dl [2.6 mmol/l]) who were on a stable dose of atorvastatin (5 to 20 mg). Patients were randomized to alirocumab (50, 75, or 150 mg) or placebo (in single 1.0-ml injection volumes) administered every 2 weeks (Q2W) for 12 weeks; the primary outcome was the mean percent change in calculated LDL-C from baseline to week 12. Single subcutaneous administration of alirocumab in healthy subjects was well tolerated over 15 weeks and resulted in highest mean percent reductions in LDL-C from baseline of approximately 40% to 60%. In the multiple-dose study, least-square mean (SE) changes in calculated LDL-C concentrations from baseline to week 12 were −54.8% (3.1%) for alirocumab 50 mg, −62.3% (3.1%) for alirocumab 75 mg, and −71.7% (3.1%) for alirocumab 150 mg, with a least-square mean (SE) difference versus placebo of −52.2% (4.3%), −59.6% (4.3%), and −69.1% (4.3%), respectively (all p <0.0001). In conclusion, alirocumab was well tolerated and significantly reduced LDL-C concentrations in Japanese patients with primary hypercholesterolemia on atorvastatin. •Alirocumab reduced low-density lipoprotein cholesterol (LDL-C) in Japanese healthy male subjects.•Alirocumab reduced LDL-C by 54.8% to 71.7% in patients with hypercholesterolemia.•No safety or tolerability concerns were apparent with alirocumab.