title: Evaluation of cardiovascular parameters in cynomolgus monkeys following IV administration of LBR-101, a monoclonal antibody against calcitonin gene-related peptide.
abstract: Calcitonin gene-related peptide (CGRP) is a well-validated target for migraine therapy and a known potent systemic vasodilator. LBR-101 is a monoclonal antibody against CGRP in clinical development for the preventive treatment of episodic and chronic migraine. Understanding the hemodynamic and cardiovascular consequences of chronic CGRP inhibition is therefore warranted. Given the conservation in CGRP sequence between monkeys and humans, addressing this question in monkeys is ideal as it allows dosing at super-therapeutic levels. To this end, two independent studies were conducted in monkeys: a single dedicated cardiovascular safety study and a repeat-dose, chronic study, both with electrocardiogram and hemodynamic assessments. LBR-101 was very well tolerated in both studies, with no clinically significant changes noted in any hemodynamic parameter, nor any relevant changes noted in any ECG parameter. In cynomolgus monkeys, cardiovascular and hemodynamic parameters do not appear to be affected by long-term inhibition of CGRP with LBR-101.
authors.affiliation: Labrys Biologics, Inc.; San Mateo, CA USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Walter
authors.affiliation: Labrys Biologics, Inc.; San Mateo, CA USA.
authors.forename: Abbas
authors.initials: A
authors.lastname: Alibhoy
authors.affiliation: Labrys Biologics, Inc.; San Mateo, CA USA.
authors.forename: Rafael
authors.initials: R
authors.lastname: Escandon
authors.affiliation: Labrys Biologics, Inc.; San Mateo, CA USA.
authors.forename: Marcelo E
authors.initials: ME
authors.lastname: Bigal
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000276:immunology / Q000494:pharmacology*; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors* / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004562:Electrocardiography; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008252:Macaca fascicularis; D008297:Male; D008881:Migraine Disorders / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology
chemical_list: D000911:Antibodies, Monoclonal; D015740:Calcitonin Gene-Related Peptide
keywords: CGRP; antibody; cardiovascular; hemodynamic; migraine; safety