M281, an Anti-FcRn Antibody: Pharmacodynamics, Pharmacokinetics, and Safety Across the Full Range of IgG Reduction in a First-in-Human Study

Clin Pharmacol Ther. 2019 Apr;105(4):1031-1039. doi: 10.1002/cpt.1276. Epub 2018 Dec 4.


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 (AEs), few moderate AEs, and a low incidence of infection-related AEs similar to placebo treatment. The tolerability and consistency of M281 pharmacokinetics and pharmacodynamics support further evaluation of M281 in diseases mediated by pathogenic IgG.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies / adverse effects
  • Antibodies / metabolism*
  • Antibodies / therapeutic use*
  • Double-Blind Method
  • Female
  • Healthy Volunteers
  • Histocompatibility Antigens Class I / metabolism*
  • Humans
  • Immunoglobulin G / metabolism*
  • Infusions, Intravenous / methods
  • Male
  • Receptors, Fc / metabolism*
  • Young Adult


  • Antibodies
  • Histocompatibility Antigens Class I
  • Immunoglobulin G
  • Receptors, Fc
  • Fc receptor, neonatal