Thromb Haemost 2017; 117(02): 252-261
DOI: 10.1160/TH16-06-0444
Coagulation and Fibrinolysis
Schattauer GmbH

Clinical evaluation of glycoPEGylated recombinant FVIII: Efficacy and safety in severe haemophilia A

Paul Giangrande
1  Oxford Haemophilia and Thrombosis Centre, Churchill Hospital, Oxford, UK
,
Tatiana Andreeva
2  St. Petersburg Hemophilia Centre, St. Petersburg, Russian Federation
,
Pratima Chowdary
3  KD Haemophilia Centre and Thrombosis Unit, Royal Free Hospital, London, UK
,
Silke Ehrenforth
4  Novo Nordisk A/S, Søborg, Denmark
,
Hideji Hanabusa
5  Department of Hematology, Ogikubo Hospital, Tokyo, Japan
,
Frank W. G. Leebeek
6  Department of Haematology, Erasmus University Medical Center, Rotterdam, The Netherlands
,
Steven R. Lentz
7  The University of Iowa, Iowa City, USA
,
Laszlo Nemes
8  National Haemophilia Center and Haemostasis Department, State Health Center, Budapest, Hungary
,
Lone Hvitfeldt Poulsen
9  Centre for Haemophilia and Thrombosis, Aarhus University Hospital, Aarhus N, Denmark
,
Elena Santagostino
10  Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, IRCCS Ca’ Granda Foundation, Maggiore Hospital Policlinico, Milan, Italy
,
Chur Woo You
11  Pediatric Department, Eulji University Hospital, Daejeon, South Korea
,
Wan Hui Ong Clausen
4  Novo Nordisk A/S, Søborg, Denmark
,
Peter G. Jönsson
4  Novo Nordisk A/S, Søborg, Denmark
,
Johannes Oldenburg
12  Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, Bonn, Germany
,
for the Pathfinder™2 Investigators› Author Affiliations
Financial support: This trial was sponsored by Novo Nordisk A/S (Bagsværd, Denmark).
Further Information

Publication History

Received:10 June 2016

Accepted after major revision:19 October 2016

Publication Date:
13 November 2017 (online)

Summary

Turoctocog alfa pegol (N8-GP) is a novel glycoPEGylated extended half-life recombinant factor VIII (FVIII) product developed for prophylaxis and treatment of bleeds in patients with haemophilia A, to enable higher activity levels with less frequent injections compared with standard FVIII products. This phase III (NCT01480180), multinational, open-label, non-randomised trial evaluated the safety and clinical efficacy of N8-GP when administered for treatment of bleeds and for prophylaxis, in previously treated patients aged ≥12 years with severe haemophilia A. Patients were allocated to receive N8-GP for prophylaxis or on-demand treatment for up to 1.8 years. Patients on prophylaxis were administered one dose of 50 IU/kg of N8-GP every fourth day. Bleeds were treated with doses of 20–75 IU/kg. Total exposure to N8-GP in the trial was 14,114 exposure days (159 patient-years). For the prophylaxis arm (n=175), the median annualised bleeding rate (ABR) was 1.33 (interquartile range, 0.00–4.61), the mean ABR was 3.70 (95 % confidence interval 2.94–4.66) and 70 (40 %) patients had no bleeds during the trial. Across treatment arms, 83.6 % of bleeds resolved with one injection and 95.5 % with up to two injections. N8-GP had a favourable safety profile and was well tolerated. The frequency and types of adverse events reported were as expected in this population. One patient developed inhibitory antibodies against FVIII (≥0.6 Bethesda units [BU]) after 93 N8-GP exposure days. No clinically significant safety concerns were identified and N8-GP was effective for prophylaxis and treatment of bleeds in previously treated patients.