Pharmacokinetics, efficacy and safety of IMMUNATE solvent/detergent (IMMUNATE S/D) in previously treated patients with severe hemophilia A: results of a prospective, multicenter, open-label phase III study.
BACKGROUND
IMMUNATE Solvent/Detergent (S/D) is a plasma-derived, human factor VIII (FVIII)/von Willebrand factor (VWF) complex subjected to S/D and vapor heat treatment.


METHODS
This prospective clinical study evaluated the pharmacokinetics (PK) (compared to IMMUNATE), efficacy and safety of IMMUNATE S/D in 56 previously treated patients with severe hemophilia A. Subjects received IMMUNATE S/D either on-demand (47/56), as a prophylactic regimen (49/56), or both (40/56).


RESULTS
IMMUNATE and IMMUNATES/D were equivalent with respect to the FVIII and VWF PK parameters assessed. Bleeding episodes (623) were reported in 47/56 subjects. For 89% of episodes, subjects required only 1 infusion with a mean dose of 29.6 IU/kg and 96% of episodes had an excellent or good response. The duration of prophylaxis ranged from 0.1 to 5.2 months. The median number of bleeds per month in subjects on prophylaxis was 0 (range 0-10). No FVIII inhibitory antibodies were observed in 56 subjects after 2,646 treatment exposure days. No related serious adverse events were reported.


CONCLUSIONS
The introduction of S/D treatment did not alter the PK characteristics and function of VWF and FVIII molecules in IMMUNATE S/D which is effective and safe for treatment of bleeding episodes, management of surgical procedures and prophylaxis.
Nemes
L
L
National Medical Center, National Hemophilia Center, Budapest, Hungary.
Lissitchkov
T
T
Dobaczewski
G
G
Klukowska
A
A
Komrska
V
V
Zimmermann
R
R
Auerswald
G
G
Engl
W
W
Abbühl
B
B
Pavlova
B G
BG
Ehrlich
H J
HJ
D000906:Antibodies / Q000097:blood; D064420:Drug-Related Side Effects and Adverse Reactions; D005169:Factor VIII / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006467:Hemophilia A / Q000628:therapy*; D006470:Hemorrhage / Q000517:prevention & control; D006801:Humans; D010599:Pharmacokinetics; D016896:Treatment Outcome; D014841:von Willebrand Factor / Q000008:administration & dosage / Q000493:pharmacokinetics
D000906:Antibodies; C523253:Immunate solvent detergent, human; D014841:von Willebrand Factor; D005169:Factor VIII