Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

12.2   Pharmacodynamics

In Study 1 [see Clinical Studies (14)], the pharmacological effect of efgartigimod alfa was assessed by measuring the decrease in serum IgG levels and AChR autoantibody levels. In patients testing positive for AChR antibodies and who were treated with VYVGART, there was a reduction in total IgG levels relative to baseline. Decrease in AChR autoantibody levels followed a similar pattern.

Pharmacokinetic Properties

12.3 Pharmacokinetics

Efgartigimod alfa exhibits linear pharmacokinetics, and following single doses of efgartigimod alfa, exposures increase proportionally up to 50 mg/kg (5 times the recommended dosage).

Distribution

The volume of distribution is 15 to 20L.
Metabolism and Elimination

Efgartigimod alfa is expected to be degraded by proteolytic enzymes into small peptides and amino acids.

The terminal half-life is 80 to 120 hours (3 to 5 days).
After a single intravenous dose of 10 mg/kg efgartigimod alfa in healthy subjects, less than 0.1% of the administered dose was recovered in urine.

Specific Populations

Age, Sex, and Race
A population pharmacokinetics analysis assessing the effects of age, sex, and race did not suggest any clinically significant impact of these covariates on efgartigimod alfa exposures.

Patients with Renal Impairment

No dedicated pharmacokinetic study has been performed in patients with renal impairment.
A population PK analysis of data from the VYVGART clinical studies indicated that patients with mild renal impairment (eGFR 60-89 mL/min/1.72m²) had 22% increase in exposure relative to the exposure in patients with normal renal function [see Use in Specific Populations (8.6)].

Patients with Hepatic Impairment

No dedicated pharmacokinetic study has been performed in patients with hepatic impairment. Hepatic impairment is not expected to affect the pharmacokinetics of efgartigimod alfa.

Drug Interaction Studies

Clinical drug interactions studies have not been performed with efgartigimod alfa.
P450 Enzymes

Efgartigimod alfa is not metabolized by cytochrome P450 enzymes; therefore, interactions with concomitant medications that are substrates, inducers, or inhibitors of cytochrome P450 enzymes are unlikely.

Drug Interactions with Other Drugs or Biological Products

Efgartigimod alfa may decrease concentrations of compounds that bind to the human FcRn [see Drug Interactions (7.1)].