The role of erenumab in the treatment of migraine

Abstract

Calcitonin gene related peptide (CGRP) monoclonal antibodies (mAbs) have been the first class of specifically developed preventive treatments for migraine. Clinical trials data suggest superiority of the CGRP mAbs to placebo in terms of prevention of migraine symptoms, migraine-specific quality of life and headache related disability. Treatment-related side effects overall did not differ significantly from placebo and discontinuation rate due to side effects has been low across the clinical trials, perhaps in view of their peripheral mode of action. Along with their route and frequency of administration, these novel class of drugs may constitute an improvement compared with the established arsenal of migraine treatments. Erenumab is a fully human antibody and the only mAb acting on the CGRP pathway by blocking its receptor. It is the first of the CGRP mAb class approved by the US Food and Drug Administration (May 2018) and the European Medicines Agency (July 2018). Erenumab exists in two different doses (70 mg and 140 mg) and it is administered with monthly subcutaneous injections. This review summarises erenumab pharmacological characteristics, clinical trials data, focusing on the potential role of this treatment in clinical practice.

Pharmacokinetics, Pharmacodynamics and Drug–Drug Interactions of New Anti-Migraine Drugs—Lasmiditan, Gepants, and Calcitonin-Gene-Related Peptide (CGRP) Receptor Monoclonal Antibodies

“…Prolonged absorption of mAbs from the injection site after s.c. administration is the cause of the flip-flop effect, and the peak concentration usually takes about 5-8 days of drug administration [90,97,98,101,108,111].…”

“…The volume of distribution for antibodies usually does not exceed the volume of the central compartment (3-7 L) [90,97,98,101,108,111].…”

“…Generally, mAbs administered with concomitant medications are not expected to result in clinically relevant pharmacokinetic interactions and are unlikely to affect drug-metabolizing enzymes or transporters because they are metabolized by general proteolytic degradation pathways [90,97,98,101,108,111].…”

“…Immunogenicity profiles of erenumab [88], fremanezumab [123], and galcanezumab [124] show no effect of ADA formation on mAbs' efficacy or safety, or on pharmacokinetics of galcanezumab [113]. Reported immunogenicity rates for these three mAbs were relatively low at 8.9% [90,119,125,126], 0.4-1.6%, and 12.5% for erenumab, fremanezumab, and galcanezumab, respectively [119].…”

“…Erenumab is eliminated in two phases: at low concentrations, elimination mainly takes place by saturable binding to the target CGRP receptor, and at higher concentrations, mainly by non-specific proteolysis. Throughout administration, erenumab is eliminated primarily by non-specific proteolysis [88][89][90].…”