Regional Variations in Alirocumab Dosing Patterns in Patients with Heterozygous Familial Hypercholesterolemia During an Open-Label Extension Study

Gisle Langslet,Michel Farnier,Alexia Letierce,John R Guyton,G Kees Hovingh,Marie T Baccara-Dinet,Garen Manvelian

doi:10.1007/s10557-020-06984-0

Abstract

PurposeDuring the alirocumab open-label extension study ODYSSEY OLE (open-label extension; NCT01954394), physicians could adjust alirocumab dosing for enrolled patients, who were diagnosed with heterozygous familial hypercholesterolemia (HeFH) and who had completed previous phase III clinical trials with alirocumab. This post hoc analysis evaluated the differences in physician–patient dosing decisions between the regions of Western Europe, Eastern Europe, North America, and the rest of the world (ROW).MethodsPatients (n = 909) who received starting dose alirocumab 75 mg every 2 weeks (Q2W) during ODYSSEY OLE (patients from FH I, FH II, and LONG TERM parent studies) were included. Low-density lipoprotein cholesterol (LDL-C) levels were blinded until week 8; subsequently, LDL-C values were communicated to physicians. From week 12, dose adjustment from 75 to 150 mg Q2W, or vice versa, was possible.ResultsMean LDL-C values used for the decision to increase dose from 75 to 150 mg Q2W were higher in Eastern Europe (3.7 mmol/L; 144.0 mg/dL) and ROW (3.8 mmol/L; 145.2 mg/dL) compared with Western Europe (3.1 mmol/L; 118.6 mg/dL) and North America (3.3 mmol/L; 126.6 mg/dL). Irrespective of region, the mean LDL-C at the time of decision to maintain at 75 mg Q2W was approximately 1.8 mmol/L (70 mg/dL). During ODYSSEY OLE (median treatment duration of 131.7 weeks), alirocumab was shown to have no unexpected long-term safety concerns.ConclusionsIn this OLE study, the observed variations in clinical treatment decisions suggest that physicians may perceive the severity of HeFH and/or the treatment of HeFH differently depending on their region.

Highlights

Heterozygous familial hypercholesterolemia (HeFH) is a common genetic disorder characterized by elevated levels of low-density lipoprotein cholesterol (LDL-C) [1,2,3]
Recent European and American guidelines recommend considering the addition of a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor for patients with HeFH and LDL-C ≥ 100 mg/dL (≥ 2.6 mmol/L) while taking maximally tolerated statin and ezetimibe therapy [5, 7]
46.9% of patients had atherosclerotic cardiovascular disease (ASCVD) and 50.1% were at very high cardiovascular risk [5]

Summary

Introduction

Heterozygous familial hypercholesterolemia (HeFH) is a common genetic disorder characterized by elevated levels of low-density lipoprotein cholesterol (LDL-C) [1,2,3]. Cardiovasc Drugs Ther (2020) 34:515–523 typically initiated on maximally tolerated statin therapy, with or without ezetimibe. Recent European and American guidelines recommend considering the addition of a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor for patients with HeFH and LDL-C ≥ 100 mg/dL (≥ 2.6 mmol/L) while taking maximally tolerated statin and ezetimibe therapy [5, 7]. Alirocumab, a monoclonal antibody that inhibits PCSK9, was shown in randomized controlled trials to significantly lower levels of LDL-C and other lipids compared with placebo or ezetimibe in patients with and without HeFH [8,9,10,11]. All patients were receiving background statin with or without other lipid-lowering therapies (LLTs). Alirocumab was administered subcutaneously in one of the two available dosages (75 or 150 mg every 2 weeks [Q2W]), and, unique within the ODYSSEY alirocumab clinical development program, with dose adjustment per physician’s clinical judgment applied to physician– patient shared decision-making

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Conclusion