Once-weekly prophylaxis with 40 IU/kg nonacog beta pegol (N9-GP) achieves trough levels of >15% in patients with haemophilia B: Pooled data from the paradigm™ trials.

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First report of safety and efficacy of a glycoPEGylated FVIII (N8-GP) in previously treated pediatric patients with severe hemophilia A-results from the international phase 3 pathfinder (TM) 5 trial

WOS: 00037994090017

Safety and efficacy of a glycoPEGylated rFVIII (turoctocog alpha pegol, N8-GP) in paediatric patients with severe haemophilia A

WOS: 000409564600007PubMed ID: 28692108Turoctocog alfa pegol (N8-GP, Novo Nordisk, Bagsvaerd, Denmark), an extended half-life glycoPEGylated recombinant factor VIII (rFVIII), is being developed for prophylaxis and treatment of bleeds in haemophilia A patients. pathfinder (TM) 5 is a multinational, open-label, single-arm trial to assess safety, efficacy and pharmacokinetics of N8-GP in paediatric (50 exposure days [ED] for patients aged 0-5 years [younger cohort]; >150 ED for patients aged 6-11 years [older cohort]) were included. For prophylaxis, N8-GP was dosed at 50-75 IU/kg twice weekly; bleeds were treated with 20-75 IU/kg. Half-life was estimated for the patients' previous FVIII product and for N8-G P. Sixty-eight patients received N8-GP; none developed inhibitors and no other concerns were identified. Median annualised bleeding rate was 1.95 (1.94 and 1.97 in the younger and older cohorts, respectively). Twenty-nine patients (42.6 %;15 younger and 14 older children, respectively) did not report any bleeding while on N8-GP prophylaxis; 39 patients (57.4 %; 19 younger and 20 older children, respectively) reported 70 bleeds (all mild/moderate). N8-GP treatment was successful for 78.6 % of bleeds in all patients, 80.0 % in younger and 77.5 % in older patients. Most bleeds (80.0 %) were treated with <= 2 injections. Half-life ratio between N8-GP and the patients' previous FVIII product was 1.85. N8-GP was well tolerated and provided effective prophylaxis and treatment of bleeds in paediatric patients with severe haemophilia A.Novo Nordisk A/S (Bagsvaerd, Denmark)Novo NordiskThis trial was sponsored by Novo Nordisk A/S (Bagsvaerd, Denmark). The sponsor was responsible for trial operations, including data analysis

Recombinant factor VIIa analog (vatreptacog alfa [activated]) for treatment of joint bleeds in hemophilia patients with inhibitors: a randomized controlled trial

WOS: 000298843500011PubMed ID: 22470921. Background: A recombinant factor VIIa analog (NN1731; vatreptacog alfa [activated]) was developed to provide safe, rapid and sustained resolution of bleeds in patients with hemophilia and inhibitors. Patients/Methods: This global, prospective, randomized, double-blinded, active-controlled, dose-escalation trial evaluated and compared one to three doses of vatreptacog alfa at 5, 10, 20, 40, and 80 mu g kg-1 with one to three doses of recombinant FVIIa (rFVIIa) at 90 mu g kg-1 in the treatment of acute joint bleeds in hemophilia patients with inhibitors. The primary endpoint comprised adverse events; secondary endpoints were evaluations of immunogenicity, pharmacokinetics, and efficacy. Results and Conclusions: Overall, 96 joint bleeds in 51 patients (> 12 years of age) were dosed. Vatreptacog alfa was well tolerated, with a low frequency of adverse events. No immunogenic or thrombotic events related to vatreptacog alfa were reported. A high efficacy rate of vatreptacog alfa in controlling acute joint bleeds was observed; 98% of bleeds were controlled within 9 h of the initial dose in a combined evaluation of 2080 mu g kg-1 vatreptacog alfa. The efficacy rate observed for rFVIIa (90%) is consistent with data from published clinical trials. The trial was not powered to compare efficacy, and further trials are needed to investigate the efficacy of vatreptacog alfa as compared with that of rFVIIa. The trial was registered at ClinicalTrials.gov (Registration Number: NCT00486278).Novo NordiskNovo Nordisk; PfizerPfizer; Baxter; BayerBayer AGThis trial was supported by research funding from Novo Nordisk to E. V. De Paula, K. Kavakli, J. Mahlangu, Y. Ayob, S. R. Lentz, M. Morfini, L. Nemes, S. Z. Salek, M. Shima, J. Windyga, and A. Chuansumrit. E. V. De Paula: Novo Nordisk - consultancy, research funding, Speakers' Bureau; Bayer consultancy, Speakers' Bureau. K. Kavakli: Novo Nordisk membership of an entity's Board of Directors or advisory committees, research funding, honorarium, costs of travel to scientific events; Baxter, Bayer - honorarium, costs of travel to scientific events; membership of an entity's Board of Directors or advisory committees, Speakers' Bureau; Wyeth/Pfizer - membership of an entity's Board of Directors or advisory committees. L. Nemes: Novo Nordisk - research funding. S. Z. Salek: Novo Nordisk - consultancy, research funding, Speakers' Bureau; Baxter - consultancy, Speakers' Bureau. M. Shima: Novo Nordisk - research funding; Baxter - research funding; Bayer research funding. J. Windyga: Novo Nordisk - honoraria, research funding, Speakers' Bureau, costs of travel to attend scientific meetings. S. Ehrenforth: Novo Nordisk - employment. A. Chuansumrit: Novo Nordisk - honoraria, research funding. - costs of travel to scientific events. J. Mahlangu: Novo Nordisk - honoraria, research funding, Speakers' Bureau, costs of travel cost to scientific meeting; Bayer - honoraria, research funding, consultancy, Speakers' Bureau, costs of travel to scientific events. Y. Ayob: Novo Nordisk - research funding. S. R. Lentz: Novo Nordisk consultancy, research funding; Celgene-equity ownership. M. Morfini: Novo Nordisk - honoraria, research funding, Speakers' Bureau; Bayer - honoraria, Speakers' Bureau; Baxter honoraria, Speakers' Bureau; CSL Behring - honoraria

Safety and Preliminary Efficacy of Recombinant Activated FVII Analog (NN1731) In the Treatment of Joint Bleeds In Congenital Hemophilia Patients with Inhibitors

52nd Annual Meeting of the American-Society-of-Hematology (ASH) -- DEC 04-07, 2010 -- Orlando, FLWOS: 000289662200720Amer Soc Hemato

Recombinant Factor Viia Analog (vatreptacog Alfa [activated]) For Treatment Of Joint Bleeds In Hemophilia Patients With Inhibitors: A Randomized Controlled Trial.

A recombinant factor VIIa analog (NN1731; vatreptacog alfa [activated]) was developed to provide safe, rapid and sustained resolution of bleeds in patients with hemophilia and inhibitors. This global, prospective, randomized, double-blinded, active-controlled, dose-escalation trial evaluated and compared one to three doses of vatreptacog alfa at 5, 10, 20, 40, and 80 lg kg(-1) with one to three doses of recombinant FVIIa (rFVIIa) at 90 lg kg(-1) in the treatment of acute joint bleeds in hemophilia patients with inhibitors. The primary endpoint comprised adverse events; secondary endpoints were evaluations of immunogenicity, pharmacokinetics, and efficacy. Overall, 96 joint bleeds in 51 patients (> 12 years of age) were dosed. Vatreptacog alfa was well tolerated, with a low frequency of adverse events. No immunogenic or thrombotic events related to vatreptacog alfa were reported. A high efficacy rate of vatreptacog alfa in controlling acute joint bleeds was observed; 98% of bleeds were controlled within 9 h of the initial dose in a combined evaluation of 20–80 lg kg(-1) vatreptacog alfa. The efficacy rate observed for rFVIIa (90%) is consistent with data from published clinical trials. The trial was not powered to compare efficacy, and further trials are needed to investigate the efficacy of vatreptacog alfa as compared with that of rFVIIa. The trial was registered at ClinicalTrials.gov ( NCT00486278).1081-

Validation of a predictive model for identifying an increased risk for thromboembolism in children with acute lymphoblastic leukemia: results of a multicenter cohort study

Among risk factors for developing thromboembolism (VTE) in children with acute lymphoblastic leukemia were Escherichia coli asparaginase, concomitant steroid use, presence of central venous lines, and thrombophilic abnormalities. Developing a predictive model for determining children at increased risk would be beneficial in targeting interventional studies to high-risk groups (HRGs). Predictive variables were incorporated into a risk assessment model, which was evaluated in 456 children and then validated in 339 patients. VTE risk by score was no greater than 2.5 for low-risk group (LRG) and greater than 2.5 for HRG. VTE rates at 3.5 months (validation cohorts) were 2.5% in LRG and 64.7% in HRG. In multivariate analysis adjusted for age, duration of asparaginase administration, enoxaparin prophylaxis, and T-immunophenotype, the HRG was significantly associated with VTE compared with the LRG (hazard/95% confidence interval [CI], 8.22/1.85-36.53). Model specificity was 96.2% and sensitivity was 63.2%. As secondary objective we investigated the use of enoxaparin for VTE prophylaxis in the HRG. HRG patients without enoxaparin prophylaxis showed a significantly reduced thrombosis-free survival compared with children on low-molecular-weight heparin (LMWH). On the basis of the high specificity, the model may identify children with leukemia at risk of VTE. LMWH may help prevent VTE in the HRG; this warrants assessment in larger cooperative clinical trials