Antihemophilic factor
Researchers have observed a low inhibitor rate in previously untreated patients (PUPs) with severe hemophilia A who received treatment with Octanate®.
The study included 51 PUPs who received octanate, a plasma-derived, von Willebrand factor-stabilized coagulation factor VIII (FVIII) concentrate.
Five of these patients (9.8%) developed FVIII inhibitors, all of whom were receiving on-demand treatment.
The hemostatic efficacy of octanate was rated as “excellent” for 99.6% of all infusions, and tolerability was rated “very good” for 99.98% of infusions.
“We are very excited by the low inhibitor rates and the excellent efficacy and tolerability achieved with octanate® in this particularly challenging patient population,” said Larisa Belyanskaya, head of IBU Haematology at Octapharma AG, the company marketing octanate.
Octapharma sponsored this study, the results of which were published in Haemophilia.
The study enrolled 51 Caucasian males with previously untreated, severe hemophilia A. They had a median age at study entry of 7.7 months (range, 0.1 months to 67.3 months).
Patients received octanate, either prophylactically or on-demand, for 100 exposure days (EDs) or 5 years, whichever came first.
There were a mean of 136.33 (±246.3) EDs, and the mean dose of octanate was 38.4 (±28.6) IU/kg/ED. Most patients (78.4%) had at least 100 EDs. The total number of EDs was 6953.
Prophylaxis accounted for 3027 EDs, immune tolerance induction for 1869 EDs, treatment of bleeds for 1817 EDs, surgical procedures for 149 EDs, and in vivo recovery assessments for 106 EDs.
Inhibitors
Five patients developed FVIII inhibitors, 4 of which were high titer and 1 low titer.
In 3 cases, the inhibitors were considered clinically relevant. In the other 2 cases, the inhibitors disappeared without a change in dose or treatment frequency.
All inhibitors developed during on-demand treatment, and all 4 high-titer inhibitors developed within the first 20 EDs.
All patients who developed inhibitors had major F8 gene defects (intron 22 inversions or large deletions of exons 7-12) that are associated with a high risk of inhibitor development.
Efficacy
The hemostatic efficacy of octanate was rated as “excellent” in 99.6% of infusions (n=4700), “good” in 0.3% (n=15), and “moderate” in 0.02% (n=1).
Most bleeds resolved within 1 day of treatment (81.2%) or within 2 days (14.3%).
Efficacy was rated as “excellent” for all but 1 of the 2611 prophylactic infusions. One was rated as “good.”
For treatment of bleeds, efficacy was rated as “excellent” for 99.2% of infusions (n=1809), “good” for 0.8% (n=14), and “moderate” for 0.05% (n=1).
There were 23 evaluable surgical procedures in 19 patients. The efficacy of octanate was rated as “excellent” in all cases (201 infusions).
Safety
There were 260 treatment-emergent adverse events (AEs) in 45 patients (88.2%). Seventy-eight of these AEs were serious.
Twenty-one AEs were considered probably or possibly related to octanate—asymptomatic parvovirus B19 seroconversions (n=16) and FVIII inhibitor development (n=5). These were classified as serious AEs according to the study protocol.
The tolerability of octanate was considered “very good” in 99.98% of infusions (n=8674) and “good” in 0.02% (n=2).
