The safety and efficacy of
Kogenate, a recombinant
factor VIII (rFVIII) preparation for the treatment of
bleeding episodes, were studied in a 123-patient meta-analysis population of previously treated patients (
PTPs), including 15 enrolled in the registration Phase III trial (PTP-I group), 93 from the post-marketing special investigation (PTP-II group), and 15 from short-term special investigations in surgery or
tooth extraction (SI group). These patients (82 severe, 31 moderate, 9 mild, and 1 unknown), aged 11 months to 72 years, were enrolled in 28 centers in Japan. Blood samples taken at the baseline and at 3, 6, 9, 12, 18, and 24 months after the introduction of
Kogenate were evaluated for FVIII inhibitor
antibodies,
antibodies formed against trace
proteins derived from the rFVIII production process, and for general changes in laboratory test results. Mean exposure to
Kogenate was 1103 days in PTP-I, 86 days in PTP-II, 27 days in patients in surgery, and 2 days in patients with
tooth extraction. Assessment of FVIII inhibitor activity was conducted in 115 of the 123 patients by means of the Bethesda assay. Twelve patients were found to have a low titer of FVIII inhibitor (0.5-3.0 BU/mL) prior to any administration of
Kogenate, and 103 were inhibitor-negative at the baseline. Among this latter group, 3 patients (2.9%) tested inhibitor-positive, with titers ranging from 1.2 to 2.1 BU/mL, with 4 patients below 1.0 BU/mL. One patient in the 11
PTPs investigated (PTP-I) developed
antibodies against baby hamster kidney
protein and mouse
immunoglobulin G, but these findings were transient and asymptomatic. Hemostasis was achieved (markedly effective or effective) in 3666 of the 3855
bleeding episodes (95.1%) observed in 108 patients. Only 1 infusion was necessary in 3790 (98.3%) of these episodes. These data indicate that
Kogenate is safe and very effective for the treatment of
bleeding in
PTPs with
hemophilia A.