Evinacumab for the treatment of homozygous familial hypercholesterolemia

ABSTRACT

Introduction

Hypercholesterolemia is mainly caused by abnormal lipoprotein metabolism and can increase the risk of cardiovascular disease. Angiopoietin-like protein 3 (ANGPTL3) can increase low-density lipoprotein cholesterol (LDL-C) and other lipids by inhibiting lipoprotein lipase activity. Evinacumab is a monoclonal antibody against ANGPTL3, it can decrease levels of LDL-C and has shown potential benefit in patients with homozygous familial hypercholesterolemia (HoFH).

Areas covered

A comprehensive literature search was conducted in PubMed (January 2000 to August 2021). Key search terms included ANGPTL3, evinacumab and HoFH. Other sources were derived from product labeling and ClinicalTrials.gov. All English-language articles identified from the data sources were reviewed and evaluated. Phase 1, 2 and 3 clinical trials were included. The pharmacological characteristics, clinical evidence, and safety of evinacumab were reviewed.

Expert opinion

Evinacumab is an ANGPTL3 inhibitor. Phase 3 clinical trials found that in patients with HoFH, evinacumab reduced LDL-C by 47%, but placebo increased by 2%. Evinacumab was well-tolerated. Common adverse events included nasopharyngitis, influenza-like illness, dizziness, rhinorrhea, and nausea. It has the potential to become a valuable treatment option for patients with HoFH.

KEYWORDS:

• Low-density lipoprotein cholesterol
• angiopoietin-like 3
• homozygous familial hypercholesterolemia
• evinacumab
• hypertriglyceridemia

Article highlights

• Evinacumab is a monoclonal antibody against ANGPTL3.

• Evinacumab is indicated as an adjunct to other LDL-C lowering therapies for the treatment of patients with HoFH.

• The recommended dose is 15 mg/kg subcutaneous every 4 weeks.

• Common adverse events included nasopharyngitis, influenza-like illness, dizziness, rhinorrhea, and nausea.

• Clinical trials: Phase 1 – NCT01749878, NCT02107872; Phase 2 – NCT03175367, NCT02265952; Phase 3 – NCT03399786; ongoing clinical trials – NCT03409744.

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

Y Gao contributed to the conception and design, and critically revised the manuscript. B Zhang contributed to data acquisition and analysis. J Yang contributed to conception and design, and drafted the manuscript.

Additional information

Funding

This manuscript was not funded.