Efficacy and safety of PCSK9 monoclonal antibodies: an evidence-based review and update

Abstract

Objective: Treatment of dyslipidemia lowers cardiovascular (CV) risk. Although statin use is a cornerstone therapy, many patients are not achieving their risk-specific low-density lipoprotein cholesterol (LDL-C) goals. The proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies have been extensively studied as lipid-lowering therapy (LLT). Herein, we present an updated evidencebased review of the efficacy and safety of PCSK9 monoclonal antibodies in the treatment of familial and non-familial hypercholesterolemia. Methods: PubMed database was searched to review Phase III studies on PCSK9 monoclonal antibodies. Then, the US National Institutes of Health Registry and the WHO International Clinical Trial Registry Platform were searched to identify and present the ongoing research. Results: PCSK9 monoclonal antibodies were investigated for the treatment of dyslipidemia, as a single therapeutic agent or as an add-on therapy to the traditional LLT. They proved effective and safe in the treatment of familial and non-familial hypercholesterolemia, and in the prevention of adverse CV events. Conclusions: The use of PCSK9 monoclonal antibodies in the treatment of dyslipidemia is currently recommended to achieve risk-specific LDL-C goal to reduce adverse CV events. Future results of the ongoing research might expand their clinical generalizability to broader patient populations.

Treating Cardiovascular Disease with Liver Genome Engineering

“…PCSK9 is an excellent candidate for gene editing because inhibition of PCSK9 leaves LDLR free to internalize more LDL particles, dramatically lowering plasma cholesterol. Currently available inhibitors of PCSK9 are monoclonal antibodies (mAb) [ 39 ] and siRNAs [ 40 ]. Several mAbs have been shown to be highly effective and safe at reducing cholesterol levels; however, injections need to be repeatedly administered and this can be cost-prohibitive [ 39 ].…”

“…Currently available inhibitors of PCSK9 are monoclonal antibodies (mAb) [ 39 ] and siRNAs [ 40 ]. Several mAbs have been shown to be highly effective and safe at reducing cholesterol levels; however, injections need to be repeatedly administered and this can be cost-prohibitive [ 39 ]. siRNA treatment has also been shown to be effective and safe at lowering cholesterol levels and injections are only needed twice a year [ 40 ].…”

Vaccination against Atherosclerosis: Is It Real?

“…Treatment with antibodies against PCSK9 effectively lowers LDL cholesterol and has been shown to further reduce cardiovascular risk when used in combination with statins [ 63 ]. Human mAbs against PCSK9 (alirocumab and evolocumab) have already been approved by the European Commission (EC) and the US Food and Drug Administration (FDA) as adjunct therapy for hypercholesterolemia.…”

“…The production of antiPCSK9 antibodies in BALB/c mice in response to L-IFPTA+ vaccine administration was long lasting and immunogenically safe [ 56 ]. The safety, PCSK9 antibody response, and LDL-lowering capacity of two PCSK9 peptide-based vaccines have been tested in a phase I trial, but the results have not yet been published [ 63 , 64 ].…”

The Use of Monoclonal Antibody-Based Proprotein Convertase Subtilisin-Kexin Type 9 (PCSK9) Inhibitors in the Treatment of Hypercholesterolemia

“…Plenty of factors, such as variations in the rate of drug absorption, metabolism, transport, excretion, or even in the levels of the non-kinetic target pathways could be attributed to subtherapeutic statin response [ 6 ]. Statins are the cornerstones of therapy [ 7 ] in combination with lifestyle changes for patients with clinical risk factors for CV diseases. High-intensity statin therapy is indicated for clinical ASCVD, but in cases of intolerance, moderate-intensity statins can be administered alternatively.…”