Efficacy and safety of alirocumab in patients with hypercholesterolemia not adequately controlled with non-statin lipid-lowering therapy or the lowest strength of statin: ODYSSEY NIPPON study design and rationale

Abstract

BackgroundStatins are generally well-tolerated and serious side effects are infrequent, but some patients experience adverse events and reduce their statin dose or discontinue treatment altogether. Alirocumab is a highly specific, fully human monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9), which can produce substantial and sustained reductions of low-density lipoprotein cholesterol (LDL-C).MethodsThe randomized, double-blind, placebo-controlled, parallel-group, phase 3 ODYSSEY NIPPON study will explore alirocumab 150 mg every 4 weeks (Q4W) in 163 Japanese patients with hypercholesterolemia who are on the lowest-strength dose of atorvastatin (5 mg/day) or are receiving a non-statin lipid-lowering therapy (LLT) (fenofibrate, bezafibrate, ezetimibe, or diet therapy alone). Hypercholesterolemia is defined as LDL-C ≥ 100 mg/dL (2.6 mmol/L) in patients with heterozygous familial hypercholesterolemia or non-familial hypercholesterolemia with a history of documented coronary heart disease, or ≥120 mg/dL (3.1 mmol/L) in patients with non-familial hypercholesterolemia classified as primary prevention category III (i.e. high-risk patients). During the 12-week double-blind treatment period, patients will be randomized (1:1:1) to receive alirocumab subcutaneously (SC) 150 mg Q4W alternating with placebo for alirocumab Q4W, or alirocumab 150 mg SC every 2 weeks (Q2W), or SC placebo Q2W. The primary efficacy endpoint is the percentage change in calculated LDL-C from baseline to week 12. The long-term safety and tolerability of alirocumab will also be investigated.DiscussionThe ODYSSEY NIPPON study will provide insights into the efficacy and safety of alirocumab 150 mg Q4W or 150 mg Q2W among Japanese patients with hypercholesterolemia who are on the lowest-strength dose of atorvastatin, or are receiving a non-statin LLT (including diet therapy alone).Trial registration ClinicalTrials.gov number: NCT02584504

PCSK9 Antibody-based Treatment Strategies for Patients With Statin Intolerance

“…In addition, Teramoto et al investigated the efficiency of alirocumab in lowering LDL-C (Table I) (21). In this study, 163 patients with hypercholesterolemia were randomized to a placebo-controlled study.…”

Real-World Data to Identify Hypercholesterolemia Patients on Suboptimal Statin Therapy

“…Although non-statin LMT (i.e., a cholesterol absorption inhibitor and fibrates) could be prescribed for patients who are unable to take or are not taking statin treatment for any reasons, the present study suggested that fewer patients on non-statin LMT achieved the target lipid levels recommended by the JAS guidelines compared to patients on statins 3) . Novel PCSK9 inhibitors, which show greater efficacy for lowering LDL-C levels, may represent a potential option for those patients unable to take statins for any reason 3, 20) .…”