Health-related quality-of-life and treatment satisfaction of individuals with hemophilia A treated with turoctocog alfa pegol (N8-GP): a new recombinant extended half-life FVIII

Susan Kearney,1,* Leslie J Raffini,2 Tan P Pham,3 Xin Ying Lee,4 Sylvia von Mackensen,5,* Andrea Landorph,6 Hideyuki Takedani,7 Johannes Oldenburg8 1Center for Bleeding and Clotting Disorders, Children’s Hospital Minnesota, Minneapolis, MN, USA; 2Division of Hematology, The Children’s Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; 3Mapi (an Icon plc company), Boston, MA, USA; 4Global Biopharm Patient Access, Biopharm Operations, Novo Nordisk A/S, Copenhagen, Denmark; 5Department of Medical Psychology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany; 6Medical & Science, Biopharm Operations, Novo Nordisk A/S, Copenhagen, Denmark; 7Department of Joint Surgery, Research Hospital of the Institute of Medical Science, The University of Tokyo, Tokyo, Japan; 8Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, Bonn, Germany *These authors contributed equally to this work Background: Prophylactic treatment regimens lead to improvements in health-related quality-of-life (HRQoL) among individuals with hemophilia. Turoctocog alfa pegol (N8-GP) provides the benefit of extending the duration of protection from bleeding and reducing the number of injections, which is expected to impact HRQoL and treatment satisfaction (TS). Aim: To investigate the HRQoL and TS of patients with severe hemophilia A from two phase III trials evaluating the safety and efficacy of N8-GP. Methods: HRQoL was assessed using the Haemo-QoL (reported by children and their parents) and Haem-A-QoL (reported by adults). TS was assessed using Hemo-Sat. Domain and total scores for all questionnaires ranged from 0 to 100, with lower scores indicating a better HRQoL or TS. A negative change in score indicates an improvement in HRQoL/TS. Results: Mean changes in HRQoL scores were reported for 14 children aged 4–7 years, 21 children aged 8–11 years, 10 adolescents aged 13–16 years, and 163 adults (17 years and above). Mean changes in children/adolescents-reported Haemo-QoL total score were -14.0 for ages 4–7 years, -3.6 for ages 8–11 years, and -0.1 for ages 13–16 years. Mean changes in parent-reported Haemo-QoL total scores were -11.5 for 4–7 years, -8.6 for ages 8–11 years, and -4.0 for 13–16 years. Adults’ mean change in Haem-A-QoL total score was -3.1 for those receiving on-demand treatment and -2.3 for those receiving prophylaxis treatment. High levels of TS with N8-GP were reported by parents of children/adolescents and the adults at the end of the trial. Conclusion: While most patients reported a relatively good baseline HRQoL when entering the respective trials, the HRQoL of patients was either maintained or further improved when treated with N8-GP. Adults and parents of children and adolescents reported a high level of treatment satisfaction with N8-GP. Keywords: hemophilia A, turoctocog alfa pegol, health-related quality-of-life, children, adults, treatment satisfactio

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 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

Changes in bleeding patterns in von Willebrand disease after institution of long-term replacement therapy : results from the von Willebrand Disease Prophylaxis Network

Clinically, the leading symptom in von Willebrand disease (VWD) is bleeding, chiefly of mucosal type, for example, epistaxis, gingival, or gastrointestinal bleeding, and menorrhagia. In severe forms of VWD with secondary deficiency of factor VIII, spontaneous joint bleeding, resembling that observed in severe haemophilia A, may also be observed. The bleeding patterns of VWD can affect quality of life, and may be life-threatening. The von Willebrand Disease Prophylaxis Network is an international study group formed with the goal of investigating the role of prophylaxis in clinically severe VWD. The objective of the present study is to investigate the response to prophylaxis focusing primarily on epistaxis, joint bleeding, gastrointestinal bleeding, and heavy bleeding associated with menses. Data from 105 subjects, 10 enrolled in a prospective study and 95 in a retrospective study between 2008 and 2013, were available for analysis. The median annualized rate reductions in bleeding were significant for epistaxis (P < 0.0001), gastrointestinal bleeding (P = 0.0003), joint bleeding (P < 0.0001), and menorrhagia (P = 0.008). Doses on a group level were approximately the same prior to and during prophylaxis, but more patients with gastrointestinal bleeding had prophylaxis three or more times per week as well as higher dosages. Our study, which primarily used retrospective data, indicates that prospective studies are needed to better delineate the doses and dose intervals that should be used for prophylactic treatment of VWD