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

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.

Extended half‐life pegylated, full‐length recombinant factor VIII for prophylaxis in children with severe haemophilia A

“…Efficacy of BAX 855 in bleeding treatment in terms of ratings of 'excellent' or 'good' and in terms of infusions administered per bleeding event was comparable with results reported for other FVIII preparations in children [19,29,32], adolescents and adults [14,18,30,31,33].…”

Efficacy and safety of rVIII-SingleChain: results of a phase 1/3 multicenter clinical trial in severe hemophilia A

“…6,15,17,18 rVIII-SingleChain was also analogous in terms of the numbers of injections needed to achieve hemostatic control; 93.5% of bleeds were controlled with 1 or 2 injections. With 1 or 2 injections, efmoroctocog alfa controlled 97.7% of bleeding episodes, moroctocog alfa (Refacto) controlled 88% (of 677 bleeding events across 2 studies), and rurioctacog alfa pegol (Adynovate) controlled 95.9% of bleeding episodes.…”

Back to the future: a recent history of haemophilia treatment

“…The efficacy of products that bypassed the need for FVIII and FIX in intrinsic coagulation was established in the early 1980s by randomized, double-blind clinical trials [30,31]. However, efficacy of products such as FEIBA and Autoplex in controlling spontaneous bleeding was less than that obtained using FVIII or FIX concentrates in patients without inhibitors (40-60% vs. 80-90%) [15][16][17][18][19][20]30,31]. In the context of this much improved but still relatively unsatisfactory background, two approaches have substantially changed the picture: the development of recombinant activated factor VII (rFVIIa) as a new bypassing product and the use of immune tolerance to eradicate the inhibitor, a treatment already pioneered in the early 1980. rFVIIa can stop 80-90% of the spontaneous haemorrhages, particularly when administered early in the home setting [32,33], and elective orthopaedic surgery can be carried out safely [34,35].…”

“…The first generation of recombinant products had an impeccable record of efficacy and safety [15][16][17]. Nevertheless, the manufacturers chose to implement further technological improvements leading to a substantial reduction in the content of proteins other than FVIII or FIX [18][19][20]. In the last few years, experimental data [21] and two retrospective cohort studies [22,23], carried out in previously untreated boys with severe haemophilia A, have raised the suspicion that the cumulative incidence of inhibitors is higher with recombinant FVIII than with plasma-derived products containing, besides other proteins, large amounts of von Willebrand factor, the carrier and stabilizer of FVIII.…”