Population pharmacokinetic and exposure-response analysis of eptinezumab in the treatment of episodic and chronic migraine.

Pharmacology Research & Perspectives
Brian BakerJohn Latham

Abstract

Eptinezumab is a humanized mAb that targets calcitonin gene-related peptide and is under regulatory review for the prevention of episodic and chronic migraine (EM, CM). It is important to determine whether exposures achieved with intravenous (IV) administration of eptinezumab achieve desired pharmacologic effects. Population pharmacokinetics, including dose- and exposure-response analyses, were performed using patient-level data from the eptinezumab clinical trial program with IV doses ranging from 10 to 1000 mg in pharmacokinetic analyses or 10 to 300 mg in phase 2/3 clinical studies in patients with EM or CM. Exposure-response analysis explored the relationship between eptinezumab exposure metrics and efficacy parameters including monthly migraine days. The pharmacokinetic profile of eptinezumab was characterized by rapid attainment of maximum plasma concentration (ie, end of IV administration) and a terminal half-life of 27 days. Covariate analysis found that patient characteristics had no clinically significant effects on pharmacokinetic parameters and were insufficient to influence dosing. Dose- and exposure-response analyses found exposure with single doses ≥100 mg was associated with greater efficacy compared with doses ...Continue Reading

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Citations

Dec 8, 2020·Pain Management·María Dolores Villar-MartínezPeter J Goadsby
Apr 16, 2021·Endocrinology, Diabetes & Metabolism·Brian BakerJeff Smith
May 20, 2021·Expert Opinion on Biological Therapy·Valerio SpuntarelliPaolo Martelletti

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