Efficacy and safety of alirocumab 150 mg every 4 weeks in hypercholesterolemic patients on non-statin lipid-lowering therapy or lowest strength dose of statin: ODYSSEY NIPPON

Abstract Background Alirocumab, a fully human monoclonal antibody to proprotein convertase subtilisin/kexin type 9, given every 2 weeks (Q2W), significantly reduced low-density lipoprotein cholesterol (LDL-C) levels in Japanese hypercholesterolemic patients on background statin. We evaluated alirocumab 150 mg every 4 weeks (Q4W) in patients on lowest-dose statin or non-statin lipid-lowering therapy (LLT). Methods ODYSSEY NIPPON was a double-blind study conducted in Japanese patients with LDL-C ≥100 mg/dL (heterozygous familial hypercholesterolemia or non-familial hypercholesterolemia with coronary heart disease) or ≥120 mg/dL (non-familial hypercholesterolemia, Japan Atherosclerosis Society category III) on atorvastatin 5 mg/day or non-statin LLT. Patients were randomized (1:1:1) to subcutaneous alirocumab 150 mg Q4W, alirocumab 150 mg Q2W, or placebo for the 12-week double-blind treatment period (DBTP), followed by a 52-week open-label treatment period (OLTP). At entry into the OLTP, patients received alirocumab 150 mg Q4W, with possible up-titration to 150 mg Q2W at Week 24. Results Least-square mean percent change in LDL-C from baseline at Week 12 (primary efficacy endpoint) was −43.8% for alirocumab Q4W, −70.1% for Q2W, and −4.3% for placebo. During the OLTP, mean LDL-C change from baseline was −45.1% at Week 20, with a further reduction at Week 36, with achieved levels maintained to Week 64. Percent of patients with ≥1 adverse event (DBTP) was 51.9% with alirocumab Q4W, 47.2% with Q2W, and 46.4% with placebo. Most common adverse events were infections and infestations (25.9%, 22.6%, 17.9%, respectively), gastrointestinal disorders (13.0%, 9.4%, 12.5%), nervous system disorders (5.6%, 7.5%, 10.7%), and general disorders and administration-site conditions (3.7%, 11.3%, 5.4%). Conclusions Hypercholesterolemic Japanese patients who tolerate only lowest-strength dose statin or non-statin LLT can achieve robust LDL-C reduction with alirocumab 150 mg Q4W, in addition to their current LLT. Alirocumab 150 mg Q4W dosing was efficacious and generally well tolerated without new safety concerns. (ClinicalTrials.gov number: NCT02584504 )