Recombinant long-acting glycoPEGylated factor IX (nonacog beta pegol) in haemophilia B: assessment of target joints in multinational phase 3 clinical trials

Negrier C 1 , Young G 2 , Abdul Karim F 3 , Collins PW 4 , Hanabusa H 5 , Colberg T 6 Show all authors , Goldman B 7 , Walsh CE 8 , paradigm™ 2 and 4 Investigators

Affiliations 

  • 1 Hôpital Louis Pradel, University Claude Bernard Lyon 1, Bron, France
  • 2 Hemostasis and Thrombosis Center, Children's Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA, USA
  • 3 Haemophilia Centre, National Blood Centre, Kuala Lumpur, Malaysia
  • 4 Arthur Bloom Haemophilia Centre, Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK
  • 5 Department of Haematology, Ogikubo Hospital, Tokyo, Japan
  • 6 Haemophilia Medical & Science, Novo Nordisk A/S, Soeborg, Denmark
  • 7 Haemophilia Biostatistics, Novo Nordisk A/S, Soeborg, Denmark
  • 8 Division of Hematology and Medical Oncology, Mount Sinai Medical Center, New York, NY, USA
Haemophilia, 2016 Jul;22(4):507-13.
PMID: 26936227 DOI: 10.1111/hae.12902

Abstract

BACKGROUND: The paradigm(™) 2 and 4 phase 3 clinical trials investigated the safety and efficacy of nonacog beta pegol, a recombinant glycoPEGylated factor IX (FIX) with extended half-life, in previously treated haemophilia B patients.

AIM: These post hoc analyses investigated the bleeding patterns in target joints.

METHODS: Patients randomized to 40 or 10 IU kg(-1) once weekly prophylaxis who had at least one target joint were included. Baseline demographics and disease-specific data were collected. Bleeding patterns were assessed, and an International Society on Thrombosis and Haemostasis (ISTH) definition of target joints was used.

RESULTS: A total of 67% and 8% of patients in the 40 and 10 IU kg(-1) arm, respectively, did not experience target joint bleeds during the paradigm(™) 2 trial. Twenty-four target joints were recorded in each prophylaxis arm at baseline. During the paradigm(™) 2 trial, no bleeds were reported in 17 (71%) and 7 (29%) target joints in the 40 and 10 IU kg(-1) arms respectively. All target joint bleeds in the 40 IU kg(-1) once weekly prophylaxis arm were controlled with a single injection of 40 IU kg(-1) nonacog beta pegol. By the latest ISTH definition, 90% and 58% of target joints in the 40 and 10 IU kg(-1) arms, respectively, were no longer considered target joints at the end of the paradigm(™) 2 trial. At the end of the paradigm(™) 4 extension trial, all target joints in the 40 IU kg(-1) arm were no longer considered target joints.

CONCLUSION: Routine prophylaxis with 40 IU kg(-1) once weekly nonacog beta pegol has the potential for effective management of target joint bleeds in haemophilia B patients.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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