A safety evaluation of evolocumab

ABSTRACT

Introduction: Evolocumab is an injectable, fully human monoclonal antibody and a member of the newest class of low density lipoprotein cholesterol (LDL-C) lowering agents called proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. The PCSK9 inhibitors are the most significant advance in lipid therapy since the introduction of the first statin 30 years ago.

Areas covered: The PCSK9 monoclonal antibodies have demonstrated a consistently high LDL-C lowering efficacy with and without statins and/or other lipid lowering therapies (LLT). LDL-C levels achieved with these agents are lower than has ever been possible before. This review will focus on the overall safety of evolocumab including cognitive impairment, very low LDL-C levels, new onset diabetes and glucose abnormalities, effect on vitamin E and steroid hormones, liver and muscle abnormalities, and immunogenicity and injection site reactions. The phase II and III clinical trials had relatively low patient-years of exposure, but the open label extension studies and the recently published outcomes trial, FOURIER, will be the focus of this paper. The safety profile of evolocumab to date is remarkable and extremely encouraging as will be demonstrated.

Expert opinion: The PCSK9 inhibitors will be responsible for a new era in lipid therapy that will expand our knowledge of lipid levels and cardiovascular disease (CVD) prevention with an efficacy and safety profile not previously available in clinical practice.

KEYWORDS:

• Evolocumab
• lipid lowering therapy (LLT)
• low density lipoprotein cholesterol (LDL-C)
• monoclonal antibody
• proprotein convertase subtilisin/kexin type 9 (PCSK9)

Declaration of interest

E Roth is a consultant, speaker and received honorarium for Amgen, Regeneron and Sanofi. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper was not funded.