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)

Curry N., Albayrak C., Escobar M., Holme P. A., Kearney S., Klamroth R., ...Daha Fazla

HAEMOPHILIA, cilt.25, sa.3, ss.373-381, 2019 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 25 Sayı: 3
  • Basım Tarihi: 2019
  • Doi Numarası: 10.1111/hae.13712
  • Dergi Adı: HAEMOPHILIA
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.373-381
  • Anahtar Kelimeler: efficacy, FVIII, haemophilia A, N8-GP, once-weekly prophylaxis, safety, FC FUSION PROTEIN, GUIDELINES, THERAPY, DEMAND
  • Ondokuz Mayıs Üniversitesi Adresli: Evet

Özet

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.