Recombinant B domain deleted porcine factor VIII for the treatment of bleeding episodes in adults with acquired hemophilia A

Abstract

Hemophilia A is an inherited deficiency of clotting factor VIII (FVIII) often complicated by inhibitor development (CHAWI) in which neutralizing antibodies block the therapeutic benefit of replacement therapy. Inhibitors to FVIII can also be seen in an auto-immune disease known as acquired hemophilia A (AHA). ‘Bypassing’ therapies have been shown to provide hemostasis but dosing must be done empirically because current assays cannot measure objective markers of treatment efficacy and safety. A recombinant porcine sequence factor VIII (r-pFVIII) has been developed for the management of AHA. Preclinical, Phase I and Phase II clinical research studies in CHAWI subjects showed therapeutic potential and safety of this agent. A Phase II/III study in AHA with serious bleeding episodes shows a positive response in all subjects after administration. Based on current preclinical and clinical trial data, r-pFVIII should become the first line of treatment in the management of hemorrhage in patients with AHA.

Keywords:

• acquired hemophilia A
• factor VIII
• hemophilia A
• inhibitor
• OBIZUR
• recombinant porcine FVIII

Acknowledgements

The author would like to thank J Fowler and E Burkart-Hartman, former and current (respectively) employees of Baxter Healthcare Corporation, for their editorial assistance.

Financial & competing interests disclosure

E Gomperts is a consultant to Baxter and was not compensated for his work in this manuscript. E Gomperts received compensation as ‘Medical Monitor’ in the development of this product. However, he was not paid for the writing of this manuscript. Baxter, initially inspiration, funded the research which is discussed in this manuscript. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Writing assistance was utilized in the production of this manuscript and performed by J Fowler and funded by Baxter.

Key issues

• The efficacy profile of recombinant porcine sequence factor VIII (r-pFVIII) can be more favorable than current bypassing therapies because it is more physiological.

• The use of r-pFVIII allows for more reliable, tailored dosing with unnecessary consumption because of the ability to measure FVIII activity.

• All acquired hemophilia A study subjects showed response in serious and in some cases life-threatening hemorrhages within 24 h of first treatment with r-pFVIII.

• The risk of developing anti-rpFVIII inhibitors during potential future applications of r-pFVIII as a long-term prophylactic treatment option is not known at this time.