Clinical evaluation of an advanced category antihaemophilic factor prepared using a plasma/albumin-free method: Pharmacokinetics, efficacy, and safety in previously treated patients with haemophilia A1

Michael D. Tarantino, Peter W. Collins, Charles R.M. Hay, A. D. Shapiro, Ralph A. Gruppo, Erik Berntorp, G. L. Bray, S. A. Tonetta, P. C. Schroth, A. D. Retzios, S. S. Rogy, M. G. Sensel, B. M. Ewenstein, Thomas Abshire, Wing Yen Wong, Jorgen Ingerslev, Peter W. Marks, Roshni Kulkarni, Margaret V. Ragni, Anne Marie Hurlet-JensenArthur Thompson, Paul Giangrande, Christine Lee, Pier Mannuccio Manucci, Claude Negrier, Jozef Vermylen, Joan Gill, Ingrid Pabinger, Claire Philipp, Rachelle Nuss, Donna Di Michele

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137 Scopus citations

Abstract

The efficacy and safety of an advanced category recombinant antihaemophilic factor produced by a plasma- and albumin-free method (rAHF-PFM) was studied in 111 previously treated subjects with haemophilia A. The study comprised a randomized, double-blinded, crossover pharmacokinetic comparison of rAHF-PFM and RECOMBINATE rAHF (R-FVIII); prophylaxis (three to four times per week with 25-40 IU kg-1 rAHF-PFM) for at least 75 exposure days; and treatment of episodic haemorrhagic events. Median age was 18 years, 96% of subjects had baseline factor VIII <1%, and 108 received study drug. Bioequivalence, based on area under the plasma concentration vs. time curve and adjusted in vivo recovery, was demonstrated for rAHF-PFM and R-FVIII. Mean (±SD) half-life for rAHF-PFM was 12.0 ± 4.3 h. Among 510 bleeding events, 473 (93%) were managed with one or two infusions of rAHF-PFM and 439 (86%) had efficacy ratings of excellent or good. Subjects who were less adherent to the prophylactic regimen had a higher bleeding rate (9.9 episodes subject-1 year-1) than subjects who were more adherent (4.4 episodes subject-1 year-1; P < 0.03). One subject developed a low titre, non-persistent inhibitor (2.0 BU) after 26 exposure days. These data demonstrate that rAHF-PFM is bioequivalent to R-FVIII, and suggest that rAHF-PFM is efficacious and safe, without increased immunogenicity, for the treatment of haemophilia A.

Original languageEnglish
Pages (from-to)428-437
Number of pages10
JournalHaemophilia
Volume10
Issue number5
DOIs
StatePublished - 1 Sep 2004
Externally publishedYes

Keywords

  • Factor VIII
  • Haemophilia A
  • Recombinant antihaemophilic factor plasma-free method
  • Recombinant factor VIII

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