Recombinant B‐domain‐deleted porcine sequence factor <scp>VIII</scp> (r‐<scp>pFVIII</scp>) for the treatment of bleeding in patients with congenital haemophilia A and inhibitors

<jats:sec><jats:title>Introduction</jats:title><jats:p>Development of inhibitors to human <jats:styled-content style="fixed-case">FVIII</jats:styled-content> (<jats:styled-content style="fixed-case">hFVIII</jats:styled-content>) significantly complicates the control of bleeding events in patients with haemophilia A.</jats:p></jats:sec><jats:sec><jats:title>Aim</jats:title><jats:p>This prospective, multicentre, open‐label, non‐comparative, Phase <jats:styled-content style="fixed-case">II</jats:styled-content> study evaluated the haemostatic activity of a recombinant B‐domain‐deleted porcine <jats:styled-content style="fixed-case">FVIII</jats:styled-content> (r‐<jats:styled-content style="fixed-case">pFVIII</jats:styled-content>), in the treatment of non‐life/non‐limb‐threatening bleeding in individuals with haemophilia A and <jats:styled-content style="fixed-case">FVIII</jats:styled-content> inhibitors.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Acute bleeding episodes in patients with <jats:styled-content style="fixed-case">pFVIII</jats:styled-content> inhibitor titres <0.8 <jats:styled-content style="fixed-case">BU mL</jats:styled-content><jats:sup>−1</jats:sup> were treated with 50 U kg<jats:sup>−1</jats:sup> body weight r‐<jats:styled-content style="fixed-case">pFVIII</jats:styled-content>. Those with <jats:styled-content style="fixed-case">pFVIII</jats:styled-content> inhibitor titres of >0.8 <jats:styled-content style="fixed-case">BU mL</jats:styled-content><jats:sup>−1</jats:sup> received an initial calculated r‐<jats:styled-content style="fixed-case">pFVIII</jats:styled-content> loading dose followed by 50 U kg<jats:sup>−1</jats:sup> treatment dose. Treatment continued at 6‐hourly intervals until bleeding was determined, controlled or till a maximum of eight doses was reached.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>All 25 bleeding episodes in nine patients (mean age: 23.7 years; range: 14–34 years) were controlled successfully with eight or fewer injections of r‐<jats:styled-content style="fixed-case">pFVIII</jats:styled-content>. The median time from bleeding onset to the administration of r‐<jats:styled-content style="fixed-case">pFVIII</jats:styled-content> was 5.7 h (range: 1.5–20.0 h). Twenty of the bleeding episodes (80%) were controlled with one treatment dose of r‐<jats:styled-content style="fixed-case">pFVIII</jats:styled-content> (with or without a loading dose, median dose: 200.8 U kg<jats:sup>−1</jats:sup>; range: 50–576 U kg<jats:sup>−1</jats:sup>) regardless of <jats:styled-content style="fixed-case">pFVIII</jats:styled-content> level. r‐<jats:styled-content style="fixed-case">pFVIII</jats:styled-content> was well tolerated and no treatment‐emergent serious adverse events were considered by the investigator to be related to r‐<jats:styled-content style="fixed-case">pFVIII</jats:styled-content> administration.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>The results suggest that <jats:styled-content style="fixed-case">FVIII</jats:styled-content> replacement therapy with r‐<jats:styled-content style="fixed-case">pFVIII</jats:styled-content> could be a viable alternative to bypassing agents for the treatment of bleeding episodes in individuals with haemophilia A and <jats:styled-content style="fixed-case">FVIII</jats:styled-content> inhibitors.</jats:p></jats:sec>