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

C L Kempton; T C Abshire; R A Deveras; W K Hoots; J C Gill; C M Kessler; N S Key; B A Konkle; P Kuriakose; D E Macfarlane; G Bergman

doi:10.1111/j.1365-2516.2012.02789.x

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

Journal article

Peer reviewed

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

C L Kempton, T C Abshire, R A Deveras, W K Hoots, J C Gill, C M Kessler, N S Key, B A Konkle, P Kuriakose, D E Macfarlane, …

Haemophilia : the official journal of the World Federation of Hemophilia, Vol.18(5), pp.798-804

09/2012

DOI: 10.1111/j.1365-2516.2012.02789.x

PMID: 22512291

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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 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.

Factor VIII - pharmacokinetics

Humans

Middle Aged

Peptide Fragments - administration & dosage

Peptide Fragments - pharmacokinetics

Male

Recombinant Proteins - pharmacokinetics

Recombinant Proteins - adverse effects

Hemophilia A - therapy

Hemophilia A - blood

Recombinant Proteins - administration & dosage

Blood Coagulation Factor Inhibitors - blood

Young Adult

Animals

Swine

Adolescent

Factor VIII - administration & dosage

Factor VIII - antagonists & inhibitors

Adult

Factor VIII - adverse effects

Peptide Fragments - adverse effects

Infusions, Intravenous

Details

Title: Subtitle: Pharmacokinetics and safety of OBI-1, a recombinant B domain-deleted porcine factor VIII, in subjects with haemophilia A
Creators: C L Kempton - Aflac Cancer Center and Blood Disorders Service and Department of Hematology and Medical Oncology, Emory University, Atlanta, GA, USA. christine.kempton@emory.edu
T C Abshire
R A Deveras
W K Hoots
J C Gill
C M Kessler
N S Key
B A Konkle
P Kuriakose
D E Macfarlane
G Bergman
Resource Type: Journal article
Publication Details: Haemophilia : the official journal of the World Federation of Hemophilia, Vol.18(5), pp.798-804
DOI: 10.1111/j.1365-2516.2012.02789.x
PMID: 22512291
ISSN: 1351-8216
eISSN: 1365-2516
Language: English
Date published: 09/2012
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
Record Identifier: 9984094386302771

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