Immune Globulin Subcutaneous, Human – Klhw 20% Solution (xembify®, IGSC-C 20%) is Effective in Primary Humoral Immunodeficiency (PI): Results from a Prospective, Open-Label, Multicenter, Phase 3 Study

Immune globulin subcutaneous, human – klhw 20% solution (IGSC-C 20%) is a new treatment for patients with PI. The primary objective determined whether the pharmacokinetics (PK) of IGSC-C 20% is noninferior to intravenous (IV) immune globulin injection (human),10% caprylate/chromatography purified (IGIV-C 10%). This study included participants, aged 2–72 years with PI (n=53). Participants received IGIV-C 10% during the Run-in Phase (n=44) prior to IV PK profiling or entered the IV Phase directly (n=9), then switched to weekly infusions of IGSC-C 20% (n=49) for approximately 24 weeks at a dose adjustment factor (DAF) of 1.37. The primary (PK IgG) and exploratory (infection rates and pathogen antibody titers) endpoints were assessed. Steady state IgG trough concentration was 1.333-fold higher with IGSC-C 20% (∼1245 mg/dL) than IGIV-C 10% (∼957 mg/dL). The geometric least-squares means ratio of the area-under-the-curve for IGSC-C 20% (n=39) vs IGIV-C 10% (n=49) was 104% (90% CI: 100%–107%). IGIV-C 10% rose rapidly to 2075 (range: 1350–3000) mg/dL IgG followed by a decline; IGSC-C 20% postinfusion remained stable between 1263 mg/dL and 1358 mg/dL through 7 days. The rates of serious bacterial infections per subject-year was 0.049 (95% CI: 0.020-0.098; upper 99% CL: 0.110) with IGSC-C 20% and 0.120 (0.051-0.232; 0.259) with IGIV-C 10%. Infection rates and trough pathogen antibody titers were comparable between treatments. IGSC-C 20% (at DAF of 1.37) provided noninferior and bioequivalent IgG exposure to IGIV-C 10%, with 33% higher mean IgG trough values, and less fluctuations in IgG concentrations.