Abstract
Background: Vatreptacog alfa, a recombinant factor VIIa (rFVIIa) analog with three amino acid substitutions and 99% identity to native FVIIa, was developed to improve the treatment of hemophilic patients with inhibitors. Objectives: To confirm the safety and assess the efficacy of vatreptacog alfa in treating bleeding episodes in hemophilic patients with inhibitors. Patients and methods: In this international, multicenter, randomized, double-blind, active-controlled, crossover, confirmatory phase III trial (adept™2) in patients with hemophilia A or B and inhibitors, bleeds were randomized 3 2 to treatment with vatreptacog alfa (one to three doses at 80 μg kg-1) or rFVIIa (one to three doses at 90 μg kg-1). Treatment failures after three doses of trial product (TP) were managed according to the local standard of care. Results: In the 72 patients enrolled, 567 bleeds were treated with TP. Both vatreptacog alfa and rFVIIa gave 93% effective bleeding control at 12 h. Vatreptacog alfa was superior to rFVIIa in secondary efficacy outcomes, including the number of doses used to treat a bleed and sustained bleeding control 24-48 h after the first dose. Eight patients (11%) developed antibodies against vatreptacog alfa, including four with cross-reactivity against rFVIIa and one with an in vitro neutralizing effect to vatreptacog alfa. Conclusions: This large randomized controlled trial confirmed the well-established efficacy and safety profile of rFVIIa, and showed that vatreptacog alfa had similar or better efficacy than rFVIIa. However, because of the development of anti-drug antibodies, a positive benefit-risk profile is unlikely to be achieved with vatreptacog alfa.
Original language | English (US) |
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Pages (from-to) | 1244-1253 |
Number of pages | 10 |
Journal | Journal of Thrombosis and Haemostasis |
Volume | 12 |
Issue number | 8 |
DOIs | |
State | Published - Jan 1 2014 |
Externally published | Yes |
Keywords
- Antibodies
- Clinical trial, phase III
- Hemophilia
- Inhibitors
- Recombinant factor VIIa
ASJC Scopus subject areas
- Hematology