K Hampton1, P Chowdary2, S Dunkley3, S Ehrenforth4, L Jacobsen4, A Neff5, E Santagostino6, J Sathar7, H Takedani8, C M Takemoto9, C Négrier10. 1. Department of Cardiovascular Science, University of Sheffield, Sheffield, UK. 2. KD Haemophilia Centre and Thrombosis Unit, Royal Free Hospital, London, UK. 3. Institute of Haematology, Royal Prince Alfred Hospital, Camperdown,Sydney, New South Wales, Australia. 4. Novo Nordisk, Søborg, Denmark. 5. Vanderbilt University Medical Center, Nashville, TN, USA. 6. Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, IRCCS Ca' Granda Foundation, Maggiore Hospital Policlinico, Milan, Italy. 7. Department of Haematology, Ampang Hospital, Selangor, Malaysia. 8. Department of Joint Surgery, Research Hospital, Institute of Medical Science, University of Tokyo, Tokyo, Japan. 9. Division of Pediatric Hematology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. 10. Hemostasis and Thrombosis Unit, Louis Pradel Hospital, Université Claude Bernard, Lyon, France.
Abstract
BACKGROUND: N8-GP (turoctocog alfa pegol) is an extended half-life glycoPEGylated recombinant factor VIII (FVIII) product developed for the prevention and treatment of bleeds in haemophilia A patients. AIM: This is a planned interim analysis of pathfinder™3, an international, open-label, Phase 3 trial evaluating the efficacy and safety (including immunogenicity) of N8-GP administered before, during and after major surgery in severe haemophilia A patients aged ≥12 years. METHODS: Sixteen patients who underwent 18 major surgical procedures (including synovectomy, joint replacement and ankle arthrodesis) were included here. Postoperative assessments were conducted daily for days 1-6, and once for days 7-14. Primary endpoint was N8-GP haemostatic efficacy, assessed after completion of surgery using a four-point scale ('excellent', 'good', 'moderate', 'none'). RESULTS: Haemostasis was successful (rated 'excellent' or 'good') on completion of surgery in 17 (94.4%) procedures and rated as 'moderate' (5.6%) for one surgery in a patient with multiple comorbidities who needed an intraoperative N8-GP dose (20.7 IU kg-1 ). In the postoperative period, three bleeds occurred (one during days 1-6; two during days 7-14); all were successfully treated with N8-GP. Mean N8-GP consumption on day of surgery was 80.0 IU kg-1 ; patients received a mean of 1.7 doses (median: 2, range: 1-3). No safety concerns were identified. CONCLUSION: The data showed that N8-GP was effective and well tolerated for the prevention and treatment of bleeds during major surgery; such FVIII products with extended half-lives may modify current treatment schedules, enabling fewer infusions and earlier patient discharge.
BACKGROUND:N8-GP (turoctocog alfa pegol) is an extended half-life glycoPEGylated recombinant factor VIII (FVIII) product developed for the prevention and treatment of bleeds in haemophilia Apatients. AIM: This is a planned interim analysis of pathfinder™3, an international, open-label, Phase 3 trial evaluating the efficacy and safety (including immunogenicity) of N8-GP administered before, during and after major surgery in severe haemophilia Apatients aged ≥12 years. METHODS: Sixteen patients who underwent 18 major surgical procedures (including synovectomy, joint replacement and ankle arthrodesis) were included here. Postoperative assessments were conducted daily for days 1-6, and once for days 7-14. Primary endpoint was N8-GP haemostatic efficacy, assessed after completion of surgery using a four-point scale ('excellent', 'good', 'moderate', 'none'). RESULTS: Haemostasis was successful (rated 'excellent' or 'good') on completion of surgery in 17 (94.4%) procedures and rated as 'moderate' (5.6%) for one surgery in a patient with multiple comorbidities who needed an intraoperative N8-GP dose (20.7 IU kg-1 ). In the postoperative period, three bleeds occurred (one during days 1-6; two during days 7-14); all were successfully treated with N8-GP. Mean N8-GP consumption on day of surgery was 80.0 IU kg-1 ; patients received a mean of 1.7 doses (median: 2, range: 1-3). No safety concerns were identified. CONCLUSION: The data showed that N8-GP was effective and well tolerated for the prevention and treatment of bleeds during major surgery; such FVIII products with extended half-lives may modify current treatment schedules, enabling fewer infusions and earlier patient discharge.
Authors: Robert Klamroth; Clemens Feistritzer; Ute Friedrich; Steven R Lentz; Kirsten Reichwald; Marek Zak; Pratima Chowdary Journal: J Thromb Haemost Date: 2019-11-15 Impact factor: 5.824
Authors: Cihan Ay; Clemens Feistritzer; Joachim Rettl; Gerhard Schuster; Anna Vavrovsky; Leonard Perschy; Ingrid Pabinger Journal: Sci Rep Date: 2021-06-21 Impact factor: 4.379
Authors: Paul Giangrande; Faraizah Abdul Karim; Laszlo Nemes; Chur Woo You; Andrea Landorph; Milan S Geybels; Nicola Curry Journal: J Thromb Haemost Date: 2020-09 Impact factor: 5.824