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Clinical Trial
. 2020 Aug;34(4):515-523.
doi: 10.1007/s10557-020-06984-0.

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

Gisle Langslet  1 , G Kees Hovingh  2   3 , John R Guyton  4 , Marie T Baccara-Dinet  5 , Alexia Letierce  6 , Garen Manvelian  7 , Michel Farnier  8
Affiliations
Clinical Trial

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

Gisle Langslet et al. Cardiovasc Drugs Ther. 2020 Aug.

Abstract

Purpose: During 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).

Methods: Patients (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.

Results: Mean 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.

Conclusions: In 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.

Keywords: Alirocumab; Dose adjustment; Familial hypercholesterolemia; LDL-C; Open-label extension; PCSK9.

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Conflict of interest statement

Dr. Langslet has received speaker and expert witness fees from Sanofi, Amgen, and Boehringer Ingelheim. Professor Hovingh is a holder of a Vidi grant (016.156.445) from the Netherlands Organisation for Scientific Research (NWO) and from Klinkerpad; has received research support from Aegerion, Amgen, and Sanofi; has served as a consultant and received speaker fees from Amgen; Aegerion; Sanofi; Regeneron Pharmaceuticals, Inc.; and Pfizer; and has been employed part-time by Novo Nordisk AS, Copenhagen, Denmark, since April 2019. Professor Guyton has received research support from Sanofi, Regeneron Pharmaceuticals, Inc., Amgen, and Amarin; and has served as a consultant for Amgen, and FH Foundation. Drs. Baccara-Dinet and Letierce are stockholders and employees of Sanofi. Dr. Manvelian is a stockholder and an employee of Regeneron Pharmaceuticals, Inc. Dr. Farnier has received research support from Sanofi/Regeneron Pharmaceuticals, Inc.; Amgen; and Merck and Co; has served as a consultant for Sanofi/Regeneron Pharmaceuticals, Inc.; Pfizer; Amgen; Merck and Co; Eli Lilly; AstraZeneca; Kowa; Akcea/Ionis; Amarin; and Servier; and has received speaker fees from Sanofi/Regeneron Pharmaceuticals, Inc.; Abbott; Amgen; Merck and Co; Pfizer; and Mylan.

Figures

Fig. 1
Fig. 1
Regional distribution of patients in ODYSSEY OLE included in current analysis (safety population). North America: Canada and the USA. Western Europe: Austria, Belgium, Denmark, Finland, France, Germany, Italy, the Netherlands, Norway, Portugal, Spain, Sweden, and the UK. Eastern Europe: Bulgaria, Czech Republic, Hungary, Romania, and the Russian Federation. ROW: Argentina, Israel, Mexico, and South Africa. ROW, rest of world.
Fig. 2
Fig. 2
Summary of LDL-C levels used to guide dose decisions by region for a overall population, b patients with ASCVD at baseline, and c patients without ASCVD at baseline (safety population). ASCVD, atherosclerotic cardiovascular disease; LDL-C, low-density lipoprotein cholesterol; Q2W, every 2 weeks; ROW, rest of world; SD, standard deviation
See this image and copyright information in PMC

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