title: Efficacy and safety of OBI-1, an antihaemophilic factor VIII (recombinant), porcine sequence, in subjects with acquired haemophilia A.
abstract: Acquired haemophilia A (AHA) is a rare bleeding disorder caused by autoantibodies against human factor VIII (hFVIII). OBI-1 is an investigational, B-domain deleted, recombinant FVIII, porcine sequence, with low cross-reactivity to anti-hFVIII antibodies. Efficacy can be monitored with FVIII activity levels in addition to clinical assessments. This prospective, open label, phase 2/3 study was designed to evaluate the efficacy of OBI-1 treatment for bleeding episodes in subjects with AHA. After an initial dose of 200 U kg(-1) , OBI-1 was titrated to maintain target FVIII activity levels, in correlation with clinical assessments, throughout the treatment phase. All 28 subjects with AHA had a positive response to OBI-1 treatment 24 h after initiation despite inhibition of FVIII activity levels immediately after infusion in 10 subjects with baseline anti-porcine FVIII inhibitors. Control of the qualifying bleed was ultimately achieved in 24 of 28 subjects. No related serious adverse events, thrombotic events, allergic reactions or thrombocytopaenia occurred. The results of this study indicate that OBI-1 is safe and effective in treating bleeding episodes in subjects with AHA. The ability to safely and effectively titrate dosing based on FVIII activity levels in this study demonstrates that OBI-1 fulfils the unmet medical need to monitor the key coagulation parameter in AHA patients.
authors.affiliation: Section of Hematology/Oncology, Tulane University, New Orleans, LA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Kruse-Jarres
authors.affiliation: Division of Hematology, Hôpital Maisonneuve-Rosemont, University of Montreal, Montreal, QC, Canada.
authors.forename: J
authors.initials: J
authors.lastname: St-Louis
authors.affiliation: Indiana Hemophilia and Thrombosis Center, Indianapolis, IN, USA.
authors.forename: A
authors.initials: A
authors.lastname: Greist
authors.affiliation: Indiana Hemophilia and Thrombosis Center, Indianapolis, IN, USA.
authors.forename: A
authors.initials: A
authors.lastname: Shapiro
authors.affiliation: Division of Hematology/Oncology, Tufts New England Medical Center, Boston, MA, USA.
authors.forename: H
authors.initials: H
authors.lastname: Smith
authors.affiliation: Katharine Dormandy Haemophilia Centre and Thrombosis Unit, Royal Free Hospital, London, UK.
authors.forename: P
authors.initials: P
authors.lastname: Chowdary
authors.affiliation: Katharine Dormandy Haemophilia Centre and Thrombosis Unit, Royal Free Hospital, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Drebes
authors.affiliation: Division of Hematology/Oncology, Children's Hospital of Los Angeles, Los Angeles, CA, USA.
authors.forename: E
authors.initials: E
authors.lastname: Gomperts
authors.affiliation: Baxter BioScience, Vienna, Austria.
authors.forename: C
authors.initials: C
authors.lastname: Bourgeois
authors.affiliation: Baxter Healthcare, Westlake Village, CA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Mo
authors.affiliation: Baxter Healthcare, Westlake Village, CA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Novack
authors.affiliation: Baxter Healthcare, Westlake Village, CA, USA.
authors.forename: H
authors.initials: H
authors.lastname: Farin
authors.affiliation: Baxter Healthcare, Westlake Village, CA, USA.
authors.forename: B
authors.initials: B
authors.lastname: Ewenstein
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D057134:Antibodies, Neutralizing; D001323:Autoantibodies / Q000276:immunology; D003429:Cross Reactions / Q000276:immunology; D005169:Factor VIII / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D005260:Female; D006467:Hemophilia A / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D013552:Swine; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D057134:Antibodies, Neutralizing; D001323:Autoantibodies; D011994:Recombinant Proteins; D005169:Factor VIII
keywords: acquired haemophilia A; bleeding episodes; recombinant FVIII porcine sequence; replacement therapy