title: Long-acting recombinant factor VIII Fc fusion protein (rFVIIIFc) for perioperative haemostatic management in severe haemophilia A.
abstract: The Phase 3 A-LONG and Kids A-LONG studies demonstrated the prolonged half-life of rFVIIIFc compared with rFVIII, and the safety and efficacy of rFVIIIFc in subjects with severe haemophilia A. Eligible subjects from A-LONG and Kids A-LONG continued rFVIIIFc treatment by enrolling in ASPIRE, an ongoing extension study. Based on combined data from the primary studies and ASPIRE interim data, the safety and efficacy of rFVIIIFc in subjects requiring surgery were evaluated. Perioperative dosing regimens were determined by investigators with guidance based on pharmacokinetic data and recommendations from a clinical dosing committee. In addition to dosing frequency, factor consumption, blood loss, transfusions, bleeding episodes, and haemostatic response were assessed. Across studies, 21 subjects underwent 23 evaluable major surgeries, including 19 orthopaedic surgeries; 41 subjects underwent 52 minor surgeries, including 30 dental procedures. No major and 10 minor surgeries were performed in paediatric subjects. Of the major (n = 22) and minor (n = 32) surgeries assessed for haemostatic response, all were rated as excellent or good by the investigator/surgeon. During most major surgeries (95.7 %), haemostasis was maintained with one rFVIIIFc infusion. Blood loss in major surgeries was consistent with similar surgeries in subjects without haemophilia. Across studies, rFVIIIFc was well tolerated; no subject developed an inhibitor.
authors.forename: Johnny N
authors.initials: JN
authors.lastname: Mahlangu
authors.forename: Margaret
authors.initials: M
authors.lastname: Ragni
authors.forename: Naresh
authors.initials: N
authors.lastname: Gupta
authors.forename: Savita
authors.initials: S
authors.lastname: Rangarajan
authors.forename: Robert
authors.initials: R
authors.lastname: Klamroth
authors.forename: Johannes
authors.initials: J
authors.lastname: Oldenburg
authors.forename: Keiji
authors.initials: K
authors.lastname: Nogami
authors.forename: Guy
authors.initials: G
authors.lastname: Young
authors.forename: Lynda M
authors.initials: LM
authors.lastname: Cristiano
authors.forename: Yingwen
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Dr. Geoffrey Allen, 593 Eddy St, Providence, RI 02903, USA, Tel.: +1 773 699 7564, Fax: +1 401 444 6104, E-mail: geoff.a.allen@gmail.com.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Allen
authors.forename: Glenn F
authors.initials: GF
authors.lastname: Pierce
authors.forename: Brian
authors.initials: B
authors.lastname: Robinson
mesh_terms: D000293:Adolescent; D000328:Adult; D016063:Blood Loss, Surgical / Q000517:prevention & control; D001803:Blood Transfusion; D002648:Child; D002675:Child, Preschool; D005169:Factor VIII / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006207:Half-Life; D006467:Hemophilia A / Q000097:blood / Q000601:surgery* / Q000628:therapy*; D006488:Hemostasis, Surgical / Q000379:methods*; D006490:Hemostatics / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D006490:Hemostatics; D007141:Immunoglobulin Fc Fragments; D011993:Recombinant Fusion Proteins; C587014:factor VIII-Fc fusion protein; D005169:Factor VIII
keywords: Phase 3 trial; factor VIII; haemophilia A; haemostasis; surgery