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 A

• Published in: Haemophilia : the official journal of the World Federation of Hemophilia Vol. 10; no. 5; pp. 428 - 437
• Main Authors: Tarantino, M. D., Collins, P. W., Hay, C. R. M., Shapiro, A.D., Gruppo, R. A., Berntorp, E., Bray, G. L., Tonetta, S. A., Schroth, P. C., Retzios, A. D., Rogy, S. S., Sensel, M. G., Ewenstein, B. M.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.09.2004
• Subjects: Adolescent; Adult; Aged; Child; Clinical Medicine; Double-Blind Method; factor VIII; Factor VIII - adverse effects; Factor VIII - pharmacokinetics; Factor VIII - therapeutic use; haemophilia A; Hematologi; Hematology; Hemophilia A - drug therapy; Hemorrhage - prevention & control; Hemostasis - drug effects; Humans; Klinisk medicin; Medical and Health Sciences; Medicin och hälsovetenskap; Middle Aged; plasma-free method; recombinant antihaemophilic factor; recombinant antihaemophilic factor plasma-free method; recombinant factor VIII; Recombinant Proteins; Treatment Outcome
• ISSN: 1351-8216; 1365-2516
• DOI: 10.1111/j.1365-2516.2004.00932.x

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.