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

Paul Giangrande; Tatiana Andreeva; Pratima Chowdary; Silke Ehrenforth; Hideji Hanabusa; Frank W. G. Leebeek; Steven R. Lentz; Laszlo Nemes; Lone Hvitfeldt Poulsen; Elena Santagostino; Chur Woo You; Wan Hui Ong Clausen; Peter G. Jönsson; Johannes Oldenburg; for the Pathfinder™2 Investigators

doi:10.1160/TH16-06-0444

Thrombosis and Haemostasis, Table of Contents

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

¹Oxford Haemophilia and Thrombosis Centre, Churchill Hospital, Oxford, UK

,

Tatiana Andreeva

²St. Petersburg Hemophilia Centre, St. Petersburg, Russian Federation

,

Pratima Chowdary

³KD Haemophilia Centre and Thrombosis Unit, Royal Free Hospital, London, UK

,

Silke Ehrenforth

⁴Novo Nordisk A/S, Søborg, Denmark

,

Hideji Hanabusa

⁵Department of Hematology, Ogikubo Hospital, Tokyo, Japan

,

Frank W. G. Leebeek

⁶Department of Haematology, Erasmus University Medical Center, Rotterdam, The Netherlands

,

Steven R. Lentz

⁷The University of Iowa, Iowa City, USA

,

Laszlo Nemes

⁸National Haemophilia Center and Haemostasis Department, State Health Center, Budapest, Hungary

,

Lone Hvitfeldt Poulsen

⁹Centre for Haemophilia and Thrombosis, Aarhus University Hospital, Aarhus N, Denmark

,

Elena Santagostino

¹⁰Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, IRCCS Ca’ Granda Foundation, Maggiore Hospital Policlinico, Milan, Italy

,

Chur Woo You

¹¹Pediatric Department, Eulji University Hospital, Daejeon, South Korea

,

Wan Hui Ong Clausen

⁴Novo Nordisk A/S, Søborg, Denmark

,

Peter G. Jönsson

⁴Novo Nordisk A/S, Søborg, Denmark

,

Johannes Oldenburg

¹²Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, Bonn, Germany

,

for the Pathfinder™2 Investigators

› Author Affiliations

Abstract

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.

Keywords

GlycoPEGylated - recombinant factor VIII - haemostasis - safety - efficacy

Full Text

References

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