Anti-hemophilic factor (recombinant), plasma/albumin-free method (octocog-alpha; ADVATE^®) in the management of hemophilia A

Abstract

Removal of blood-based additives from recombinant clotting factor concentrates continues to be advocated by the hemophilia community due to the history of infectious disease transmission with previous blood-derived clotting factor concentrates. In 2003, octocog-alpha, antihemophilic factor (recombinant), plasma/albumin-free method (ADVATE^®) was introduced, providing the first third-generation recombinant factor VIII (rFVIII) concentrate. Completed clinical trials have demonstrated ADVATE^® to be safe and effective in adult and pediatric subjects utilizing both prophylactic and on-demand treatment regimens, and for perioperative hemostatic coverage. In the five completed studies involving more than 200 previously treated patients (PTPs), a single incidence of low-titer, non-persistent inhibitor was reported. Active post authorization safety surveillance (PASS) is being performed to expand the efficacy and safety profile of ADVATE^® in routine clinical practice. Laboratory studies have documented the storage and post-reconstitution stability of ADVATE^®, conferring the desired versatility for home treatment. The evolving real-world experience and ongoing studies will provide further insight into ADVATE^® pharmacokinetics, alternative prophylactic dosing regimens, methods for perioperative hemostatic management, and utility in immune tolerance induction. Experience with ADVATE^®, and its place in today’s treatment paradigm, is the focus of this article.

Keywords:

• ADVATE^®
• factor VIII
• hemophilia
• octocog-alpha

Acknowledgements

The following investigators comprised the ADVATE Clinical Study Group:

Thomas Abshire, MD, USA; Carmen Altisent, MD, Spain, Erik Berntorp, MD, PhD, Sweden; Victor Blanchette, MD, Canada; Peter Collins, MD, UK; Donna Di Michele, MD, USA; Jorge Di Paola, MD, USA; Paul Giangrande, MD, UK; Joan Gill, MD, USA; Alessandro Gringeri, MD, Italy; Ralph Gruppo, MD, USA; Hideji Hanabusa, MD, Japan; Yoshiro Hatae, MD, Japan; Charles Hay, MD, UK; Hans-Hermann Brackmann, MD, Germany; Fernando Hernández, MD, Spain; Keith Hoots, MD, USA; Anne Marie Hurlet-Jensen, MD, USA; Katsuyuki Fukutake, MD, Japan; Jorgen Ingerslev, MD, Denmark; Eizou Kakishita, MD, Japan; Wolfhart Kreuz, MD, Germany; Roshni Kulkarni, MD, USA; Thierry Lambert, MD, France; Christine Lee, MD, UK; Raina Liesner, MD, UK; Christoph Male, MD, Austria; Marilyn Manco-Johnson, MD, USA; Catherine Manno, MD, USA; Pier Mannuccio Mannucci, MD, Italy; Pier Mannuccio Mannucci, MD, Italy; Peter Marks, MD, PhD, USA; Junichi Mimaya, MD, Japan; Claude Négrier, MD, France; Rachelle Nuss, MD, USA; Idith Ortiz, MD, Puerto Rico; Ingrid Pabinger, MD, Austria; Pia Petrini, MD, Sweden; Claire Philipp, MD, USA; Steven Pipe, MD, USA; Hartmut Pollmann, MD, Germany; Margaret Ragni, MD, USA; Bruce Ritchie, MD, Canada; Chantal Rothschild, MD, France; Hideaki Sakai, MD, Japan; Inge Scharrer, MD, Germany; Wolfgang Schramm, MD, Germany; Amy Shapiro, MD, USA; Midori Shima, MD, Japan; Akira Shirahata, MD, Japan; Martti Siimes, MD, Finland; Junki Takamatsu, MD, Japan; Masashi Taki, MD, Japan; Michael Tarantino, MD, USA; Alexis Thompson, MD, USA; Arthur Thompson, MD, USA; Marijke van den Berg, MD, The Netherlands; Jozef Vermylen, MD, Belgium; Mario Von Depka, MD, Germany; Irwin Walker, MD, Canada; Indira Warrier, MD, USA; Wing-Yen Wong, MD, USA.

The author gratefully acknowledges Kathleen Casey PhD, Gerald Spotts PhD, and Bruce M. Ewenstein MD, PhD for their thoughtful review and input on the manuscript.