Efficacy and safety of the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab among high cardiovascular risk patients on maximally tolerated statin therapy: The ODYSSEY COMBO I study

Abstract

Alirocumab treatment achieved a significantly greater reduction in LDL-C and allowed a greater proportion of patients to achieve LDL-C goals, versus placebo after 24 weeks in high cardiovascular risk patients with suboptimally controlled hypercholesterolemia at baseline despite receiving maximally tolerated statin with or without other lipid-lowering therapy. The frequency of treatment-emergent adverse events and study medication discontinuations were generally comparable between treatment groups.

Efficacy and safety of alirocumab among individuals with diabetes mellitus and atherosclerotic cardiovascular disease in the ODYSSEY phase 3 trials

“…This post‐hoc pooled analysis included individuals with a medical history of Type 1 or Type 2 DM and ASCVD who participated in 9 randomized, double‐blind, placebo‐ or ezetimibe‐controlled ODYSSEY Phase 3 trials with subcutaneous alirocumab administered every 2 weeks (Q2W), with trial durations of 24‐104 weeks (LONG TERM [NCT01507831],26 FH I [NCT01623115],23 FH II [NCT01709500],23 HIGH FH [NCT01617655],22 COMBO I [NCT01644175],24 COMBO II [NCT01644188],20 OPTIONS I [NCT01730040],19 OPTIONS II [NCT01730053]21 and ALTERNATIVE [NCT01709513]) 25. Individual trial results have been published previously.…”

“…Alirocumab is a PCSK9 inhibitor that signficantly reduced LDL‐C and other atherogenic lipid parameters in participants with hypercholesterolaemia in Phase 3 ODYSSEY trials,19, 20, 21, 22, 23, 24, 25, 26 including dedicated trials involving individuals with DM who were receiving insulin therapy27 or with mixed dyslipidaemia,28 with a safety profile comparable to controls. Alirocumab has also been demonstrated to reduce major adverse cardiovascular events vs placebo in patients with recent acute coronary syndrome in the ODYSSEY OUTCOMES trial 29.…”

Efficacy and Safety of Alirocumab 150 mg Every 4 Weeks in Patients With Hypercholesterolemia Not on Statin Therapy: The ODYSSEY CHOICE II Study

“…Alirocumab, a fully human monoclonal antibody that specifically binds to PCSK9, has been shown to significantly lower LDL‐C levels across a range of dosing regimens, whether as monotherapy12 or on a background of statin±other lipid‐lowering therapies 13, 14, 15, 16. A monthly dosing regimen may be convenient and effective,17, 18 with different doses being appropriate when used as monotherapy compared with background statin therapy.…”

PCSK9 Inhibitors in Lipid Management of Patients With Diabetes Mellitus and High Cardiovascular Risk: A Review

“…Alirocumab and evolocumab, either alone or in combination with statins and/or other lipid‐lowering therapies, have been shown in their respective phase 3 clinical trial programs (ODYSSEY and PROFICIO [Program to Reduce LDL‐C and Cardiovascular Outcomes Following Inhibition of PCSK9 In Different Populations]) to significantly reduce LDL‐C levels by up to 60% from baseline (depending on dosing regimen; Table) in patients with hypercholesterolemia, including those with familial hypercholesterolemia, moderate to very high cardiovascular risk, and statin intolerance 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62. The inclusion/exclusion criteria and other details of each phase 3 ODYSSEY and PROFICIO trial are shown in Table S2.…”

“…Subanalyses of the diabetes mellitus subpopulations in the alirocumab and evolocumab phase 3 trials (Table) showed significant reductions in LDL‐C that were generally similar between individuals with and without diabetes mellitus 46, 47, 62, 66, 67, 68, 69, 70. Findings were consistent in the prespecified diabetes mellitus subanalysis of FOURIER, which analyzed 11 031 patients with diabetes mellitus versus 16 533 patients without diabetes mellitus; compared with placebo, median LDL‐C levels were reduced by 57% in those with diabetes mellitus and by 60% in those without diabetes mellitus 71.…”