Premium
M281, an Anti‐FcRn Antibody: Pharmacodynamics, Pharmacokinetics, and Safety Across the Full Range of IgG Reduction in a First‐in‐Human Study
Author(s) -
Ling Leona E.,
Hillson Jan L.,
Tiessen Renger G.,
Bosje Tjerk,
Iersel Mattheus Paulus,
Nix Darrell J.,
Markowitz Lynn,
Cilfone Nicholas A.,
Duffner Jay,
Streisand James B.,
Manning Anthony M.,
Arroyo Santiago
Publication year - 2019
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt.1276
Subject(s) - pharmacokinetics , pharmacodynamics , antibody , tolerability , pharmacology , adverse effect , medicine , placebo , immunoglobulin g , immunology , immunoglobulin e , pathology , alternative medicine
M281 is a fully human, anti‐neonatal Fc receptor (FcRn) antibody that inhibits FcRn‐mediated immunoglobulin G (IgG) recycling to decrease pathogenic IgG while preserving IgG production. A randomized, double‐blind, placebo‐controlled, first‐in‐human study with 50 normal healthy volunteers was designed to probe safety and the physiological maximum for reduction of IgG. Intravenous infusion of single ascending doses up to 60 mg/kg induced dose‐dependent serum IgG reductions, which were similar across all IgG subclasses. Multiple weekly doses of 15 or 30 mg/kg achieved mean IgG reductions of ≈85% from baseline and maintained IgG reductions ≥75% from baseline for up to 24 days. M281 was well tolerated, with no serious or severe adverse events ( AE s), few moderate AE s, and a low incidence of infection‐related AE s similar to placebo treatment. The tolerability and consistency of M281 pharmacokinetics and pharmacodynamics support further evaluation of M281 in diseases mediated by pathogenic IgG.