Immunogenicity of erenumab: A pooled analysis of six placebo-controlled trials with long-term extensions.

Abstract

Immunogenicity of erenumab, a human anti-calcitonin gene-related peptide receptor monoclonal antibody developed for migraine prevention, has been evaluated throughout clinical development. Integrated post hoc analysis assessing immunogenicity of erenumab across six clinical trials in patients with episodic and chronic migraine (N = 2985). Anti-erenumab antibody incidence and potential impact on pharmacokinetics, efficacy, and safety were evaluated in short-term (double-blind treatment phase 12-24 weeks) and long-term (double-blind treatment phase plus extensions of up to 5 years) analyses. Anti-erenumab binding antibody incidence was low with few patients developing neutralizing antibodies. Antibody responses were mostly transient with low magnitude. Binding antibodies developed as early as 2-4 weeks after the first dose; the majority developed within the first 6 months and very few after the first year. Serum concentrations of erenumab in antibody-positive patients were generally lower than, but within the range of, antibody-negative patients. There was no impact of anti-erenumab antibodies on erenumab efficacy or safety with no differences between antibody-positive and antibody-negative patients in change in monthly migraine days or adverse event rates. This pooled analysis showed that immunogenicity had no meaningful clinical impact on efficacy or safety of erenumab in patients with migraine.Clinical Trial Registration: ClinicalTrials.gov, NCT01952574; ClinicalTrials.gov, NCT02456740; Clinicaltrials.gov NCT02483585; Clinicaltrials.gov, NCT02174861; Clinicaltrials.gov, NCT02630459; Clinicaltrials.gov, NCT03812224.