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

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...

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Bibliographic Details
Published in:	Haemophilia : the official journal of the World Federation of Hemophilia Vol. 18; no. 5; pp. 798 - 804
Main Authors:	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.
Format:	Journal Article
Language:	English
Published:	Oxford, UK Blackwell Publishing Ltd 01-09-2012
Subjects:	Adolescent Adult Animals Antibodies Bioavailability Blood Coagulation Factor Inhibitors - blood Coagulation Coagulation factors factor VIII Factor VIII - administration & dosage Factor VIII - adverse effects Factor VIII - antagonists & inhibitors Factor VIII - pharmacokinetics haemophilia A Hemophilia Hemophilia A - blood Hemophilia A - therapy Humans Infusions, Intravenous inhibitor Male Middle Aged OBI-1 Peptide Fragments - administration & dosage Peptide Fragments - adverse effects Peptide Fragments - pharmacokinetics Pharmacokinetics porcine factor VIII Recombinant Proteins - administration & dosage Recombinant Proteins - adverse effects Recombinant Proteins - pharmacokinetics Standard deviation Swine Young Adult
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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 Cmax 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−1dL−1; chromogenic: 1817.28 ± 625.14 U h−1dL−1) than Hyate:C (OSCA: 1177.8 ± 469.49 U h−1dL−1; chromogenic: 707.61 ± 420.05 U h−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 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.
Bibliography:	ArticleID:HAE2789 ark:/67375/WNG-JNMFDR6N-R istex:60235414AB00AF05E01BA043D0113802FF015A16 ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 ObjectType-News-3
ISSN:	1351-8216 1365-2516
DOI:	10.1111/j.1365-2516.2012.02789.x