title: Pegylated, full-length, recombinant factor VIII for prophylactic and on-demand treatment of severe hemophilia A.
abstract: Current management of hemophilia A includes prophylaxis with factor VIII (FVIII) replacement every 2 to 3 days. BAX 855, Baxalta's pegylated full-length recombinant FVIII (rFVIII), was designed to increase half-life and, thus, reduce the frequency of prophylactic infusions while maintaining hemostatic efficacy. BAX 855 was evaluated in previously treated patients with severe hemophilia A who were aged 12 to 65 years. A phase 1 study compared the pharmacokinetic (PK) profile of BAX 855 with that of licensed rFVIII (Advate). In a pivotal study, the annualized bleeding rate (ABR), PK parameters, and efficacy of bleeding treatment were assessed. In the phase 1 study, the mean half-life (T1/2) and the mean residence time of BAX 855 compared with Advate were 1.4- to 1.5-fold higher. These results were confirmed in the pivotal study. The pivotal study met its primary endpoint: Prophylaxis with BAX 855 resulted in an ABR that was significantly lower than half the ABR of on-demand treatment (P < .0001). The median ABR was 1.9, and 39.6% of compliant subjects had no bleeding episodes during prophylaxis, whereas subjects treated on-demand had a median ABR of 41.5. BAX 855 was also efficacious for the treatment of bleeding episodes, with 95.9% of bleeding episodes treated with 1 to 2 infusions and 96.1% having efficacy ratings of excellent/good. No FVIII inhibitory antibodies or safety signals were identified. These studies provide evidence that BAX 855 was safe and efficacious for on-demand treatment and prophylaxis administered twice weekly in patients with hemophilia A. The trials were registered at www.clinicaltrials.gov as #NCT01736475 and #NCT01599819.
authors.affiliation: Puget Sound Blood Center and University of Washington, Seattle, WA;
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Konkle
authors.affiliation: Academy of Medical Sciences of Ukraine, Lviv, Ukraine;
authors.forename: Oleksandra
authors.initials: O
authors.lastname: Stasyshyn
authors.affiliation: Katharine Dormandy Haemophilia Centre and Thrombosis Unit, Royal Free Hospital, London, United Kingdom;
authors.forename: Pratima
authors.initials: P
authors.lastname: Chowdary
authors.affiliation: St. Thomas' Hospital, London, United Kingdom;
authors.forename: David H
authors.initials: DH
authors.lastname: Bevan
authors.affiliation: Quintiles Drug Research Unit at Guy's Hospital, London, United Kingdom;
authors.forename: Tim
authors.initials: T
authors.lastname: Mant
authors.affiliation: Nara Medical University Hospital, Nara, Japan;
authors.forename: Midori
authors.initials: M
authors.lastname: Shima
authors.affiliation: Baxalta Innovations GmbH, Vienna, Austria; and.
authors.forename: Werner
authors.initials: W
authors.lastname: Engl
authors.affiliation: Baxalta US Inc., Westlake Village, CA.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Dyck-Jones
authors.affiliation: Baxalta Innovations GmbH, Vienna, Austria; and.
authors.forename: Monika
authors.initials: M
authors.lastname: Fuerlinger
authors.affiliation: Baxalta US Inc., Westlake Village, CA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Patrone
authors.affiliation: Baxalta US Inc., Westlake Village, CA.
authors.forename: Bruce
authors.initials: B
authors.lastname: Ewenstein
authors.affiliation: Baxalta Innovations GmbH, Vienna, Austria; and.
authors.forename: Brigitt
authors.initials: B
authors.lastname: Abbuehl
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D005169:Factor VIII / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D006467:Hemophilia A / Q000188:drug therapy*; D006470:Hemorrhage / Q000517:prevention & control*; D006490:Hemostatics / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000737:chemistry; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D006490:Hemostatics; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D005169:Factor VIII