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

- 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.

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.