Background:
Octanate is a highly purified, double virus inactivated, human plasma-derived factor VIII (FVIII) concentrate with all coagulation FVIII bound to its natural stabilizer VWF in a VWF:RCo/FVIII:C ratio of approximately 0.4. Five prospective GCP studies with octanate were conducted in 77 previously treated patients (PTPs) with severe haemophilia A. None of these 77 PTPs developed an inhibitor.
Aim:
To assess the immunogenicity in previously untreated patients (PUPs), a prospective clinical trial has been initiated in 2000. This included 48 PUPs with severe hemophilia A after treatment with octanate for an observational period of 100 exposure days and at least 6 months.
Methods:
Patients with severe haemophilia A without previous exposure to FVIII or FVIII containing products were enrolled. Efficacy and tolerability are assessed by a 4-point verbal rating scale. Inhibitor assay, according to modified Bethesda method is tested pre-treatment, every 3-4 exposure days (ED 1-20) and every 10 EDs (ED 21-100) but at minimum every three months.
Results:
Two of 48 (4.2%) subjects receiving treatment developed clinically relevant inhibitor titers over the course of the study. Another two displayed inhibitors that disappeared spontaneously without change of dose or dosing interval. All inhibitors developed under on- demand treatment and before ED 50. From the 48 subjects, 42 had exceeded 50 EDs at the time of this analysis. octanate was well-tolerated and the adverse event profile was consistent with the population studied. The haemostatic efficacy in prophylaxis and treatment of bleeding were generally rated as “excellent” and no complication was reported for any surgical treatment.
Conclusion:
Despite frequent inhibitor testing and predominant on-demand treatment, octanate showed a low rate of clinically relevant inhibitor formation (4.2%) in this cohort of patients.