Safety and efficacy of a glycoPEGylated rFVIII (turoctocog alpha pegol, N8-GP) in paediatric patients with severe haemophilia A

Sandrine Meunier; Jayanthi Alamelu; Silke Ehrenforth; Hideji Hanabusa; Faraizah Abdul Karim; Kaan Kavakli; Melanie Khodaie; Janice Staber; Oleksandra Stasyshyn; Donald L. Yee; Lina Rageliene

doi:10.1160/TH17-03-0166

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2017; 117(09): 1705-1713
DOI: 10.1160/TH17-03-0166

Coagulation and Fibrinolysis

Schattauer GmbH

Safety and efficacy of a glycoPEGylated rFVIII (turoctocog alpha pegol, N8-GP) in paediatric patients with severe haemophilia A

Sandrine Meunier

¹Unité d’Hémostase Clinique, Groupement Hospitalier Est, Hospices Civils de Lyon, Lyon, France

,

Jayanthi Alamelu

²Centre for Haemostasis and Thrombosis, Guy’s and St Thomas’ NHS Foundation Trust, London, UK

,

Silke Ehrenforth

³Novo Nordisk A/S, Søborg, Denmark

,

Hideji Hanabusa

⁴Department of Hematology, Ogikubo Hospital, Suginami-ku, Tokyo, Japan

^†Dr Hanabusa is now deceased.

,

Faraizah Abdul Karim

⁵National Blood Centre, Kuala Lumpur, Malaysia

,

Kaan Kavakli

⁶Department of Hematology, Ege University Children’s Hospital, Izmir, Turkey

,

Melanie Khodaie

³Novo Nordisk A/S, Søborg, Denmark

,

Janice Staber

⁷Pappajohn Biomedical Institute, and Stead Family Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA

,

Oleksandra Stasyshyn

⁸Institute of Blood Pathology and Transfusion Medicine, Ukrainian National Academy of Medical Sciences, Lviv, Ukraine

,

Donald L. Yee

⁹Department of Pediatrics, Hematology-Oncology Section and Department of Medicine, Thrombosis Research Section, Baylor College of Medicine, Houston, Texas, USA

,

Lina Rageliene

¹⁰Children’s Hospital, Affiliate of Vilnius University Hospital Santariskiu Klinikos, Centre for Pediatric Oncology and Hematology, Vilnius, Lithuania

› Author Affiliations

Abstract

Summary

Turoctocog alfa pegol (N8-GP, Novo Nordisk, Bagsværd, Denmark), an extended half-life glycoPEGylated recombinant factor VIII (rFVIII), is being developed for prophylaxis and treatment of bleeds in haemophilia A patients. pathfinder^™5 is a multinational, open-label, single-arm trial to assess safety, efficacy and pharmacokinetics of N8-GP in paediatric (<12 years), previously treated patients. Boys with severe haemophilia A (<1 % FVIII), no history of inhibitors and previously treated with FVIII products (>50 exposure days [ED] for patients aged 0–5 years [younger cohort]; >150 ED for patients aged 6–11 years [older cohort]) were included. For prophylaxis, N8-GP was dosed at 50–75 IU/kg twice weekly; bleeds were treated with 20–75 IU/kg. Half-life was estimated for the patients’ previous FVIII product and for N8-GP. Sixty-eight patients received N8-GP; none developed inhibitors and no other concerns were identified. Median annualised bleeding rate was 1.95 (1.94 and 1.97 in the younger and older cohorts, respectively). Twenty-nine patients (42.6 %; 15 younger and 14 older children, respectively) did not report any bleeding while on N8-GP prophylaxis; 39 patients (57.4 %; 19 younger and 20 older children, respectively) reported 70 bleeds (all mild/moderate). N8-GP treatment was successful for 78.6 % of bleeds in all patients, 80.0 % in younger and 77.5 % in older patients. Most bleeds (80.0 %) were treated with ≤2 injections. Half-life ratio between N8-GP and the patients’ previous FVIII product was 1.85. N8-GP was well tolerated and provided effective prophylaxis and treatment of bleeds in paediatric patients with severe haemophilia A.

Trial registered at www.clinicaltrials.gov (NCT01731600).

Supplementary Material to this article is available online at www.thrombosis-online.com.

Keywords

GlycoPEGylated - haemophilia A - paediatrics - phase III - recombinant FVIII

Full Text

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Supplementary Material

Online Supplementary Material (PDF)