Efficacy and safety of pegylated full‐length recombinant factor VIII with extended half‐life for perioperative haemostasis in haemophilia A patients

Abstract

Introduction: BAX 855 is a pegylated full-length recombinant factor VIII (rFVIII) with an extended half-life, built on a licensed rFVIII (ADVATE â ). BAX 855 demonstrated efficacy and safety in prophylaxis and the treatment of bleeding episodes in previously treated patients (PTPs) with severe haemophilia A. Aim: This phase 3 surgery study evaluates the haemostatic efficacy and safety of BAX 855 for perioperative haemostasis in PTPs with severe haemophilia A undergoing surgery. Methods: Elective procedures were prospectively classified as major or minor. The dose and frequency of BAX 855 administered perioperatively were to be guided by each patient's pharmacokinetic profile for major procedures or BAX 855 incremental recovery for minor procedures. Haemostatic efficacy was evaluated using a predefined scale. Blood loss was compared to the expected average and maximum blood loss predicted preoperatively. Results: A total of 15 male patients (aged 19-52 years) underwent 15 procedures (11 major and four minor). The overall intra-and perioperative haemostatic efficacy of BAX 855 was 'excellent' in all 15 subjects (100%). Postoperatively, evaluated at postoperative Day 1, all treatments were 'excellent' except for one minor (dental) procedure which was rated 'good'. No related adverse events, allergic reactions, thrombotic events, nor signs of immunogenicity in terms of induction of binding antibodies to FVIII, PEG or PEG-VIII, or FVIII inhibitors were observed. Conclusion: These results demonstrate that BAX 855 is safe and haemostatically effective in patients with severe haemophilia A undergoing surgery.

Outcome of Clinical Trials with New Extended Half-Life FVIII/IX Concentrates

“…A phase III surgical study with BAX 855 (NCT01913405) initiated in December 2013 is currently ongoing and an interim analysis has been recently published [19]. This first analysis reports on 15 procedures (11 major) in 15 subjects for which overall intra- and peri-operative haemostatic efficacy was rated as “excellent” in all cases and no related adverse events were observed [19].…”

“…This first analysis reports on 15 procedures (11 major) in 15 subjects for which overall intra- and peri-operative haemostatic efficacy was rated as “excellent” in all cases and no related adverse events were observed [19]. Surgical procedures were covered on average with 30–35 IU/kg twice daily maintaining a mean trough level well above 50% until post-operative Day 7 [19]. …”

Extended Half-Life Factor VIII and Factor IX Preparations

“…Furthermore, it was shown that BAX855 is safe and hemostatically effective in patients with severe hemophilia A undergoing surgery [32].…”

Many factor VIII products available in the treatment of hemophilia A: an embarrassment of riches?

“…Moreover, the enhanced affinity for VWF may accelerate the formation of VWF:FVIII complex that not only increases the half-life but also may result in decreased immunogenicity by inhibiting endocytosis of FVIII by dendritic cells 25,26. These modifications resulted in a FVIII molecule with an increased half-life that is comparable to the PEGylated EHL product (Adynovate) 8,10,27,28. When FVIII is normally activated, the heavy and light chains are cleaved and released from VWF.…”