The AUC of HYQVIA compared to conventional IGSC administration was 20% higher. The absolute bioavailability of HYQVIA was 93.3% relative to IGIV.

The pharmacokinetic parameters of HYQVIA compared to intravenously administered Immune Globulin Infusion 10% (Human) are shown in Table 7. The mean IgG dose in weekly equivalents was 147 mg/kg ± 50 (range 134 to 160 mg/kg). The serum IgG trough levels are comparable: mean serum IgG trough with HYQVIA was 1077 mg/dL compared to 1095 mg/dL with intravenously administered Immune Globulin Infusion 10% (Human). C max was lower with HYQVIA (1607 mg/dL) than with intravenously administered Immune Globulin Infusion 10% (Human) (2248 mg/dL). Time to reach maximum concentration of IgG following HYQVIA administration was 5 (3.3-5.1) days.

In the extension trial, reducing the dosing interval from 4 to 2 weeks resulted in a mean increase of 13% in serum IG trough levels.

Table 7 Pharmacokinetic Parameters of HYQVIA Compared to Intravenously Administered Immune Globulin Infusion 10% (Human) (IGIV)    HYQVIA  IGIV 
Number of Subjects 60 68
IgG Weekly Dose [mg/kg/week]
 
 Mean (SD)
 147 (50)
 139 (55)
 
 95% CI
 134 to 160
 126 to 153
 
C max [mg/dL]
 
 Mean (SD)
 1607 (382)
 2248 (547)
 
 95% CI
 1508 to 1706
 2116 to 2380
 
IgG Trough Levels[mg/dL]a
  
 
 Mean (SD)
 1077 (275)
 1095 (321)
 
 
 95% CI
 1004 to 1149
 1017 to 1174
 
AUC/week [g*days/L]b
  
 
 Mean (SD)
 91.4 (21)
 98.7 (24.3)
 
 
 95% CI
 85.9 to 96.8
 92.8 to 104.5
 
Bioavailabilityc
  
 Point estimate
 93.3
 100% (defined)
 
 90% CI
 91.4 to 95.2
 N/A
 
Clearance [mL/kg/day]

 Mean (SD)
 1.6 (0.5)d
 1.4 (0.4)
 
 
 95% CI
 1.5 to 1.8
 1.3 to 1.5
 
Terminal Half-life [days]
  
 Mean (SD)
 59.3 (36.1)
 41.6 (26.9)
 
 95% CI
 50 to 68.6
 35.1 to 48.1
 
T max [days]
  
 Median
 5.0
 0.1
 
 95% CI
 3.3 to 5.1
 0.1 to 0.1

a N=58 for HYQVIA and N=67 for IGIV
 
b Standardized to a 7 day interval
 
c N=58 for HYQVIA
 
d Apparent clearance
Figure 1 shows mean concentration-time plot of IgG in subjects 12 years and older. The concentration-time profile of HYQVIA is similar to that of intravenous administration but without the high peak. The peak to trough variation is more similar to subcutaneous administration.

Figure 1 Pharmacokinetic Comparison of Mean IgG Values for HYQVIA vs. Intravenously and Subcutaneously Administered Immune Globulin Infusion 10% (Human)*

* IGIV and HYQVIA data at 28 day dosing interval; IGSC data at 7 day dosing interval; IGSC dotted line shows weekly dose extrapolated over 21 additional days.
Close
13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fert