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Pharmacokinetics and safety of OBI‐1, a recombinant B domain‐deleted porcine factor VIII, in subjects with haemophilia A
Author(s) -
KEMPTON C. L.,
ABSHIRE T. C.,
DEVERAS R. A.,
HOOTS W. K.,
GILL J. C.,
KESSLER C. M.,
KEY N. S.,
KONKLE B. A.,
KURIAKOSE P.,
MACFARLANE D. E.,
BERGMAN G.
Publication year - 2012
Publication title -
haemophilia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.213
H-Index - 92
eISSN - 1365-2516
pISSN - 1351-8216
DOI - 10.1111/j.1365-2516.2012.02789.x
Subject(s) - medicine , chromogenic , haemophilia a , pharmacokinetics , recombinant dna , haemophilia , placebo , coagulation , antibody , haemophilia b , pharmacology , gastroenterology , immunology , surgery , pathology , gene , chemistry , biochemistry , chromatography , alternative medicine
Summary. 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 C max appeared higher for OBI‐1 (OSCA: 176.00 U dL −1 , standard deviation ± 88.00; chromogenic: 151.00 ± 31.51 U dL −1 ) than Hyate:C (OSCA: 82.3 ± 19.22 U dL −1 ; chromogenic: 52.67 ± 13.8 U dL −1 ). Mean AUC also appeared higher for OBI‐1 (OSCA: 2082.87 ± 1323.43 U h −1 dL −1 ; chromogenic: 1817.28 ± 625.14 U h −1 dL −1 ) than Hyate:C (OSCA: 1177.8 ± 469.49 U h −1 dL −1 ; chromogenic: 707.61 ± 420.05 U h −1 dL −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 29 days 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.