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).
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 pr...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Wiley
2019
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| _version_ | 1797088729673760768 |
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| author | Curry, N Albayrak, C Escobar, M Andre Holme, P Kearney, S Klamroth, R Misgav, M Négrier, C Wheeler, A Santagostino, E Shima, M Landorph, A Tønder, SM Lentz, SR |
| author_facet | Curry, N Albayrak, C Escobar, M Andre Holme, P Kearney, S Klamroth, R Misgav, M Négrier, C Wheeler, A Santagostino, E Shima, M Landorph, A Tønder, SM Lentz, SR |
| author_sort | Curry, N |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T02:54:15Z |
| format | Journal article |
| id | oxford-uuid:aebddc31-a49d-4f6c-9100-aedd83826685 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T02:54:15Z |
| publishDate | 2019 |
| publisher | Wiley |
| record_format | dspace |
| spelling | oxford-uuid:aebddc31-a49d-4f6c-9100-aedd838266852022-03-27T03:44:43ZOnce-weekly prophylaxis with glycoPEGylated recombinant factor VIII (N8-GP) in severe haemophilia A: Safety and efficacy results from pathfinder 2 (randomized phase III trial).Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:aebddc31-a49d-4f6c-9100-aedd83826685EnglishSymplectic ElementsWiley2019Curry, NAlbayrak, CEscobar, MAndre Holme, PKearney, SKlamroth, RMisgav, MNégrier, CWheeler, ASantagostino, EShima, MLandorph, ATønder, SMLentz, SRIntroduction 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. |
| spellingShingle | Curry, N Albayrak, C Escobar, M Andre Holme, P Kearney, S Klamroth, R Misgav, M Négrier, C Wheeler, A Santagostino, E Shima, M Landorph, A Tønder, SM Lentz, SR 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). |
| title | 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). |
| title_full | 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). |
| title_fullStr | 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). |
| title_full_unstemmed | 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). |
| title_short | 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). |
| title_sort | 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 |
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