Pharmacokinetics, Pharmacodynamics, and Safety of Intravenous Efgartigimod and Subcutaneous Efgartigimod PH20 in Healthy Chinese Participants.

ABSTRACT

BACKGROUND: Efgartigimod, a human immunoglobulin G (IgG)1-derived Fc fragment targeting the neonatal Fc receptor, has been developed into intravenous (IV) and subcutaneous (SC) formulations for treating generalized myasthenia gravis (gMG) and other autoimmune diseases. Data in the Chinese population were not available to date, and while both formulations have been approved in the USA, the EU, Japan and China for the treatment of gMG. OBJECTIVE: We present the pharmacokinetic, pharmacodynamic, and safety of IV and SC PH20 efgartigimod in healthy Chinese participants. METHODS: In two independent, double-blinded, placebo-controlled, phase I studies of the IV and SC formulations of efgartigimod, healthy Chinese adults were randomized 31 to receive active treatment or matching placebo once every 7 days for four doses. Primary endpoints were pharmacokinetic parameters. RESULTS: After the fourth IV infusion, a mean maximum observed concentration (Cmax) of 194 µg/mL was reached at the end of the 1 h infusion; the mean area under concentration-time curve from time zero to 168 h (AUC0-168h) was 5300 µg × h/mL. After the fourth SC injection, a mean Cmax of 42.1 µg/mL was achieved with a median Tmax of 47.74 h; the mean AUC0-168h was 4790 µg × h/mL. Maximal mean reductions from baseline in total IgG levels were reached approximately 24 days after the first dose (60.7%, IV formulation; 66.4%, SC formulation). Treatment-related adverse events (TRAEs) were reported in seven (58.3%) participants receiving SC efgartigimod, mostly injection-site reactions. No TRAEs or AEs of special interest were reported in the IV study. CONCLUSIONS: The efgartigimod IV and SC pharmacokinetic, pharmacodynamic, and safety profiles in Chinese participants were similar to the known profiles in non-Chinese participants. Both formulations effectively reduced total IgG levels by a similar percentage. CLINICAL TRIAL REGISTRATION CTR20211952 and CTR20211805.