Recombinant factor VIIa analog in the management of hemophilia with inhibitors: results from a multicenter, randomized, controlled trial of vatreptacog alfa

S. R Lentz; S Ehrenforth; F Abdul Karim; T Matsushita; K. N Weldingh; J Windyga; J. N Mahlangu; Adept TM2 Investigators

doi:10.1111/jth.12634

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Recombinant factor VIIa analog in the management of hemophilia with inhibitors: results from a multicenter, randomized, controlled trial of vatreptacog alfa

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Recombinant factor VIIa analog in the management of hemophilia with inhibitors: results from a multicenter, randomized, controlled trial of vatreptacog alfa

S. R Lentz, S Ehrenforth, F Abdul Karim, T Matsushita, K. N Weldingh, J Windyga, J. N Mahlangu and Adept TM2 Investigators

Journal of thrombosis and haemostasis, Vol.12(8), pp.1244-1253

08/2014

DOI: 10.1111/jth.12634

PMCID: PMC4238784

PMID: 24931322

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Abstract

Summary 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.

recombinant factor VIIa

hemophilia

inhibitors

antibodies

clinical trial, phase III

Details

Title: Subtitle: Recombinant factor VIIa analog in the management of hemophilia with inhibitors: results from a multicenter, randomized, controlled trial of vatreptacog alfa
Creators: S. R Lentz - University of Iowa
S Ehrenforth - Novo Nordisk A/S
F Abdul Karim - National Blood Centre
T Matsushita - Nagoya University Hospital
K. N Weldingh - Novo Nordisk A/S
J Windyga - Institute of Hematology and Transfusion Medicine
J. N Mahlangu - University of the Witwatersrand and National Health Laboratory Service
Adept TM2 Investigators
Resource Type: Journal article
Publication Details: Journal of thrombosis and haemostasis, Vol.12(8), pp.1244-1253
DOI: 10.1111/jth.12634
PMID: 24931322
PMCID: PMC4238784
NLM abbreviation: J Thromb Haemost
ISSN: 1538-7933
eISSN: 1538-7836
Number of pages: 10
Grant note: Biogen/Idec Novo Nordisk in compliance with international guidelines for good publication practice Kyowa/Kirin Kaketsuken GSK Bayer ChugaAUTHOR: other from Chuga – other what? Please clarify., Octapharma LFB Baxter
Language: English
Date published: 08/2014
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
Record Identifier: 9984094571702771

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