Once-weekly prophylaxis with glycoPEGylated recombinant factor VIII (N8-GP) in severe haemophilia A: Safety and efficacy results from pathfinder 2 (randomized phase III trial)

Nicola Curry, Canan Albayrak, Miguel Escobar, Pål Andre Holme, Susan Kearney, Robert Klamroth, Mudi Misgav, Claude Négrier, Allison Wheeler, Elena Santagostino, Midori Shima, Andrea Landorph, Sidsel Marie Tønder, Steven R. Lentz

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: Turoctocog alfa pegol (N8-GP) is a site-specific, 40 kDa glycoPEGylated recombinant factor VIII (FVIII) product with an extended half-life. The comprehensive main phase of the pivotal pathfinder 2 trial showed N8-GP dosed every 4 days (Q4D) provided favourable safety and efficacy for preventing bleeds in 175 patients with haemophilia A. Aim and methods: We investigated the safety and efficacy of N8-GP prophylaxis when administered weekly (Q7D) for 24 weeks to patients with low bleeding rates in the pathfinder 2 extension trial. Patients (≥12 years) with ≤2 bleeds during the preceding 6 months of the pathfinder 2 main phase were eligible for randomization to receive N8-GP 50 IU/kg Q4D or 75 IU/kg Q7D. Safety and efficacy endpoints were incidence of FVIII inhibitors and annualized bleeding rate (ABR), respectively. Results: Fifty-five of 143 (38.5%) patients on prophylaxis who continued into the extension phase were randomized to receive 50 IU/kg Q4D (n = 17) or 75 IU/kg Q7D (n = 38). Nine patients in the Q7D cohort reverted to 50 IU/kg Q4D. No inhibitors were detected. In both cohorts, >50% of patients experienced no bleeds. Median ABR for overall, joint, spontaneous, traumatic and muscle was 0.00 for both cohorts. Overall estimated success rate for treating bleeding episodes was 87.5%; 94.7% of bleeds were controlled with ≤2 injections. Conclusions: Weekly N8-GP was well tolerated and efficacious and may benefit selected “low bleeder” patients with haemophilia A.

Original languageEnglish
Pages (from-to)373-381
JournalHaemophilia
Volume25
Issue number3
DOIs
Publication statusPublished - Jan 1 2019

Keywords

  • efficacy
  • FVIII
  • haemophilia A
  • N8-GP
  • once-weekly prophylaxis
  • safety

ASJC Scopus subject areas

  • Hematology
  • Genetics(clinical)

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