Tags

Type your tag names separated by a space and hit enter

Recombinant factor VIIa analog in the management of hemophilia with inhibitors: results from a multicenter, randomized, controlled trial of vatreptacog alfa.
J Thromb Haemost 2014; 12(8):1244-53JT

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.

Authors+Show Affiliations

Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24931322

Citation

Lentz, S R., et al. "Recombinant Factor VIIa Analog in the Management of Hemophilia With Inhibitors: Results From a Multicenter, Randomized, Controlled Trial of Vatreptacog Alfa." Journal of Thrombosis and Haemostasis : JTH, vol. 12, no. 8, 2014, pp. 1244-53.
Lentz SR, Ehrenforth S, Karim FA, et al. Recombinant factor VIIa analog in the management of hemophilia with inhibitors: results from a multicenter, randomized, controlled trial of vatreptacog alfa. J Thromb Haemost. 2014;12(8):1244-53.
Lentz, S. R., Ehrenforth, S., Karim, F. A., Matsushita, T., Weldingh, K. N., Windyga, J., & Mahlangu, J. N. (2014). Recombinant factor VIIa analog in the management of hemophilia with inhibitors: results from a multicenter, randomized, controlled trial of vatreptacog alfa. Journal of Thrombosis and Haemostasis : JTH, 12(8), pp. 1244-53. doi:10.1111/jth.12634.
Lentz SR, et al. Recombinant Factor VIIa Analog in the Management of Hemophilia With Inhibitors: Results From a Multicenter, Randomized, Controlled Trial of Vatreptacog Alfa. J Thromb Haemost. 2014;12(8):1244-53. PubMed PMID: 24931322.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Recombinant factor VIIa analog in the management of hemophilia with inhibitors: results from a multicenter, randomized, controlled trial of vatreptacog alfa. AU - Lentz,S R, AU - Ehrenforth,S, AU - Karim,F Abdul, AU - Matsushita,T, AU - Weldingh,K N, AU - Windyga,J, AU - Mahlangu,J N, AU - ,, Y1 - 2014/07/16/ PY - 2014/03/18/received PY - 2014/05/30/accepted PY - 2014/6/17/entrez PY - 2014/6/17/pubmed PY - 2015/4/4/medline KW - antibodies KW - clinical trial, phase III KW - hemophilia KW - inhibitors KW - recombinant factor VIIa SP - 1244 EP - 53 JF - Journal of thrombosis and haemostasis : JTH JO - J. Thromb. Haemost. VL - 12 IS - 8 N2 - 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. SN - 1538-7836 UR - https://www.unboundmedicine.com/medline/citation/24931322/Recombinant_factor_VIIa_analog_in_the_management_of_hemophilia_with_inhibitors:_results_from_a_multicenter_randomized_controlled_trial_of_vatreptacog_alfa_ L2 - https://dx.doi.org/10.1111/jth.12634 DB - PRIME DP - Unbound Medicine ER -