Author + information
- Received July 2, 2019
- Revision received November 21, 2019
- Accepted December 9, 2019
- Published online February 10, 2020.
- Raul D. Santos, MD, MSc, PhDa,∗ (, )@rauldsf_santos,
- Evan A. Stein, MD, PhDb,
- G. Kees Hovingh, MD, PhD, MBAc,
- Dirk J. Blom, MD, PhDd,
- Handrean Soran, MDe,
- Gerald F. Watts, MDf,g,
- J. Antonio G. López, MDh,
- Sarah Bray, PhDh,
- Christopher E. Kurtz, MDh,
- Andrew W. Hamer, MDh and
- Frederick J. Raal, MD, MMed, PhDi
- aLipid Clinic Heart Institute (InCor), University of São Paulo Medical School Hospital and Hospital Israelita Albert Einstein, São Paulo, Brazil
- bDepartment of Medicine, Cardiology, University of Chicago Pritzker School of Medicine, Chicago, Illinois
- cDepartment of Vascular Medicine, Amsterdam UMC, Location AMC, Amsterdam, the Netherlands
- dDivision of Lipidology and Hatter Institute for Cardiovascular Research in Africa, Department of Medicine, University of Cape Town, Cape Town, South Africa
- eCardiovascular Trials Unit, Manchester University Hospital NHS Foundation Trust, Manchester, United Kingdom
- fSchool of Medicine, Faculty of Health and Medical Sciences, University of Western Australia, Perth, Western Australia, Australia
- gLipid Disorders Clinic, Department of Cardiology, Royal Perth Hospital, Perth, Western Australia, Australia
- hAmgen, Thousand Oaks, California
- iCarbohydrate and Lipid Metabolism Research Unit, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa
- ↵∗Address for correspondence:
Dr. Raul D. Santos, Lipid Clinic Heart Institute (InCor), University of São Paulo Medical School Hospital and Hospital Israelita Albert Einstein, São Paulo 05403-900, Brazil.
Background Proprotein convertase subtilisin/kexin type 9 inhibitor therapy is a treatment option for patients with familial hypercholesterolemia (FH) who are unable to reach low-density lipoprotein cholesterol (LDL-C) goals.
Objectives The aim of this study was to provide long-term safety and efficacy data for evolocumab in patients with homozygous FH (HoFH) and severe heterozygous FH (HeFH).
Methods In this open-label, single-arm study, patients with HoFH or severe HeFH ≥12 years of age and on stable lipid-lowering therapy began subcutaneous evolocumab 420 mg monthly or 420 mg every 2 weeks if on lipoprotein apheresis. After 12 weeks, those not on apheresis could be up-titrated to 420 mg every 2 weeks. The primary endpoint was the incidence of treatment-emergent adverse events; secondary endpoints were changes in LDL-C and other lipids.
Results In total, 300 patients (106 with HoFH, including 14 <18 years of age at enrollment) received evolocumab for a median of 4.1 years. Adverse events occurred in 89.3% of patients, the most common of which were nasopharyngitis, influenza, upper respiratory tract infection, and headache. Mean change in LDL-C from baseline to week 12 was −21.2% (−59.8 mg/dl) in patients with HoFH and −54.9% (−104.4 mg/dl) in those with severe HeFH and was sustained over time. Of 48 patients with HoFH who were up-titrated, mean change in LDL-C improved from −19.6% at week 12 to −29.7% after 12 weeks of 420 mg every 2 weeks. The adjudicated cardiovascular event rate was 2.7% per year. Of 61 patients receiving apheresis at enrollment, 16 discontinued apheresis.
Conclusions Evolocumab was well tolerated and effectively reduced plasma LDL-C levels in patients with HoFH and severe HeFH over a median of 4.1 years.
Study funding was provided by Amgen. Dr. Santos has received honoraria for consulting, speaking activities, or research from Amgen, Akcea, AstraZeneca, Biolab, Esperion, Kowa, Merck, Merck Sharp & Dohme, Novo Nordisk, and Sanofi/Regeneron; and is a recipient of a scholarship from Conselho Nacional de Pesquisa e Desenvolvimento Tecnologico (process 303734/2018-3). Dr. Stein has received fees for consulting from Gemphire, CymaBay, and AstraZeneca related to homozygous familial hypercholesterolemia; has received expert witness fees from Amgen; and is a founder and CEO of LIB Therapeutics. Dr. Hovingh has served as consultant and speaker for biotechnology and pharmaceutical companies that develop molecules that influence lipoprotein metabolism, including Regeneron, Pfizer, Merck Sharp & Dohme, Sanofi, and Amgen; has served as principal investigator for clinical trials conducted with a.o. Amgen, Sanofi, Eli Lilly, Novartis, Kowa, Genzyme, Cerenis, Pfizer, Dezima, and AstraZeneca; has received research grants from ZonMW, the European Union, Amgen, Sanofi, AstraZeneca, Aegerion, and Synageva; has received honoraria and investigator fees (to the Department of Vascular Medicine) for sponsor-driven studies and lectures for companies with approved lipid-lowering therapy in the Netherlands; and is partly employed by Novo Nordisk (0.7FTE) and the AMC (0.3FTE). Dr. Blom has received honoraria for consulting, speaking activities, or research from Amgen, Sanofi/Regeneron, Aegerion, Gemphire, AstraZeneca, and Novo Nordisk. Dr. Soran has received research grants from Akcea, Amgen, Amryt, Sanofi-Genzyme, Alexion, Pfizer, and Merck Sharp & Dohme; and has received honoraria from Sanofi, Bristol-Myers Squibb, Eli Lilly, AstraZeneca, Pfizer, Takeda, Amgen, and Merck Sharp & Dohme. Dr. Watts has received honoraria for advisory board membership or research grants from Amgen, Regeneron, Sanofi, Pfizer, Gemphire, Kowa, and Arrowhead. Drs. López, Bray, Kurtz, and Hamer are employees and shareholders of Amgen. Dr. Raal has received research grants, honoraria, or consulting fees for professional input and/or lectures from Sanofi, Regeneron, Amgen, and The Medicines Company.
- Received July 2, 2019.
- Revision received November 21, 2019.
- Accepted December 9, 2019.
- 2020 The Authors