Pharmacokinetics and safety of OBI-1, a recombinant B domain-deleted porcine factor VIII, in subjects with haemophilia A

Abstract

OBI-1 is a recombinant B-domain deleted porcine factor VIII (FVIII). FVIII treatment in those with haemophilia A may be complicated by the development of anti-FVIII antibodies (inhibitors) leading to a failure to respond to treatment with human FVIII. To compare the pharmacokinetics and safety of a single dose of OBI-1 with Hyate:C in subjects with haemophilia A and inhibitors, subjects were randomized to receive either Hyate:C followed by placebo or placebo followed by OBI-1 in a double-blind fashion. FVIII levels were assayed using both a one-stage coagulation assay (OSCA) and chromogenic assay. Pharmacokinetic parameters for FVIII were calculated for 6/9 subjects randomized; in three subjects baseline anti-porcine FVIII inhibitors led to a lack of measurable FVIII activity. Mean Cmax appeared higher for OBI-1 (OSCA: 176.00UdL-1, standard deviation ±88.00; chromogenic: 151.00±31.51UdL-1) than Hyate:C (OSCA: 82.3±19.22UdL-1; chromogenic: 52.67±13.8UdL-1). Mean AUC also appeared higher for OBI-1 (OSCA: 2082.87±1323.43Uh-1dL-1; chromogenic: 1817.28±625.14Uh-1dL-1) than Hyate:C (OSCA: 1177.8±469.49Uh-1dL-1; chromogenic: 707.61 ±420.05Uh-1dL-1). Two infusion-related events occurred: one with Hyate:C, one with placebo. Four of five subjects without anti-porcine FVIII inhibitors at baseline remained porcine FVIII inhibitor negative 29days after infusion. A single dose of OBI-1 appears to have higher bioavailability than Hyate:C in subjects with haemophilia A without measurable anti-porcine FVIII inhibitors, and is well tolerated. These results should be confirmed in a larger phase 2/3 study. © 2012 Blackwell Publishing Ltd.