Neonatal Fc Receptor Antagonist Efgartigimod Sustainably Reduces Circulating IgG Level in Humans

Observing that management of severe antibody-mediated autoimmune diseases with intravenous immune globulin (IVIG) and plasma exchange therapy can be associated with serious adverse events or a substantial burden on patients, investigators from the Belgian biotechnology company argenx and U.S. collaborators conducted a PhaseI clinical study to assess a novel modified antibody Fc fragment (efgartigimod) that reduces the circulating IgG level by blocking neonatal Fc receptor-mediated IgG recycling.

This randomized, double-blind, placebo-controlled first-inhuman study was conducted in 62 healthy volunteers to explore single and multiple ascending intravenous doses of this Fc receptor antagonist. The study objectives were to assess safety, tolerability, pharmacokinetics, pharmacodynamics and immunogenicity. Findings from this study were compared with the pharmacodynamics profile elicited by efgartigimod in cynomolgus monkeys.

Efgartigimod treatment resulted in a rapid and specific clearance of serum IgG levels in both cynomolgus monkeys and healthy volunteers. In humans, a single administration of efgartigimod reduced IgG levels by up to 50 percent, while multiple dosing further lowered IgG levels on average by 75 percent. Approximately eight weeks following the last administration, IgG levels returned to baseline. Efgartigimod did not alter the homeostasis of albumin or immunoglobulin classes other than IgG. No serious adverse events related to efgartigimod were observed.

The investigators concluded efgartigimod is “safe and results in a specific, profound and sustained reduction of serum IgG levels,” and proposed this therapeutic approach warrants further evaluation in IgG-driven autoimmune diseases.