Perioperative haemostasis with full‐length, PEGylated, recombinant factor VIII with extended half‐life (rurioctocog alfa pegol) in patients with haemophilia A: Final results of a multicentre, single‐arm phase III trial

• Published in: Haemophilia : the official journal of the World Federation of Hemophilia 2019-09, Vol.25 (5), p.773-781
• Main Authors: Gruppo, Ralph, López‐Fernández, Maria‐Fernanda, Wynn, Tung T., Engl, Werner, Sharkhawy, Marlies, Tangada, Srilatha
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; BAX 855; Blood transfusion; Coagulation factors; extended half‐life recombinant factor VIII; Factor VIII - pharmacology; Factor VIII - therapeutic use; Factor VIII deficiency; Female; haemophilia A; Headache; Hemophilia; Hemophilia A - drug therapy; Hemostasis; Humans; Immunogenicity; Immunoglobulin G; Immunoglobulin M; Male; Middle Aged; Original; perioperative haemostasis; Perioperative Period - methods; rurioctocog alfa pegol; Surgery; TAK-660; Treatment Outcome; Young Adult
• ISSN: 1351-8216; 1365-2516
• DOI: 10.1111/hae.13807

Introduction Rurioctocog alfa pegol (BAX 855, TAK‐660) is a PEGylated, full‐length, recombinant factor VIII (rFVIII) with extended half‐life developed from unmodified rFVIII (antihaemophilic factor [recombinant]). Aim To determine the perioperative haemostatic efficacy and safety of rurioctocog alfa pegol in male previously treated patients (PTPs) with severe haemophilia A. Methods This multicentre, single‐arm, phase III study included PTPs who were to undergo major or minor elective or minor emergency surgical, dental or other invasive procedures. Rurioctocog alfa pegol dose and frequency were individualized based on patients’ pharmacokinetic profiles for major surgeries and by rurioctocog alfa pegol incremental recovery for minor surgeries. Haemostatic efficacy was assessed using the Global Haemostatic Efficacy Assessment score. Results Twenty‐one patients aged 16‐61 years underwent 21 major and five minor surgeries. For all 24 evaluable surgeries, overall haemostatic efficacy was rated as excellent and blood loss comparable to that expected in non‐haemophilic patients. No blood transfusions were required intraoperatively but were administered postoperatively for four surgeries in three patients. Five injury‐related postoperative bleeding episodes occurred in five patients, of which two required additional rurioctocog alfa pegol treatment. Two non‐serious adverse events of mild severity (increased ALT level and headache) were considered possibly related to rurioctocog alfa pegol. There were no deaths or treatment‐related serious adverse events. No patients developed inhibitory antibodies to FVIII or persistent IgG‐ or IgM‐binding antibodies to FVIII, PEG‐FVIII or PEG. Conclusion Rurioctocog alfa pegol was well tolerated and effective for perioperative use in patients with haemophilia A and showed no signs of immunogenicity.