BACKGROUND: Recombinant activated factor VII (rFVIIa; eptacog alfa activated, NovoSeven® , Novo Nordisk A/S) is a bypassing agent used in congenital hemophilia A patients with inhibitors. Emicizumab (Hemlibra® ; F Hoffmann-La Roche Ltd) is a recombinant, humanized, bispecific monoclonal antibody used for routine prophylaxis in patients with congenital hemophilia A with inhibitors. Concomitant use of the hemostatic agents rFVIIa and emicizumab carries a theoretical increased risk of thrombotic complications. Roche and Novo Nordisk collaboratively analyzed all available data on the use of rFVIIa in patients receiving emicizumab prophylaxis in the Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Prophylactic Emicizumab Versus no Prophylaxis in Hemophilia A Participants With Inhibitors (HAVEN) clinical development program. OBJECTIVE: Obtain further insights into the concomitant clinical use and safety of rFVIIa and emicizumab. METHODS: The initial individual rFVIIa dose, dosing intervals and cumulative dosing were evaluated in the HAVEN 1, HAVEN 2, and HAVEN 4 trials. All adverse events reported in each of the three trials in patients treated with rFVIIa, including available narratives, were assessed. RESULTS: The vast majority of bleeds occurred in HAVEN 1. When rFVIIa was used to treat a bleeding episode, a 100 ± 20 μg/kg dose was used to initiate treatment in the majority of cases. The dosing interval, as well as cumulative dosing were consistent with prescribing information and current practice. No serious adverse events, no thrombotic microangiopathy cases, or thromboembolic events were assessed to be associated with rFVIIa when used in conjunction with emicizumab prophylaxis in the HAVEN trials. CONCLUSION: rFVIIa use in the context of emicizumab prophylaxis does not change the rFVIIa safety profile as described in the product information.
BACKGROUND: Recombinant activated factor VII (rFVIIa; eptacog alfa activated, NovoSeven® , Novo Nordisk A/S) is a bypassing agent used in congenital hemophilia Apatients with inhibitors. Emicizumab (Hemlibra® ; F Hoffmann-La Roche Ltd) is a recombinant, humanized, bispecific monoclonal antibody used for routine prophylaxis in patients with congenital hemophilia A with inhibitors. Concomitant use of the hemostatic agents rFVIIa and emicizumab carries a theoretical increased risk of thrombotic complications. Roche and Novo Nordisk collaboratively analyzed all available data on the use of rFVIIa in patients receiving emicizumab prophylaxis in the Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Prophylactic Emicizumab Versus no Prophylaxis in Hemophilia AParticipants With Inhibitors (HAVEN) clinical development program. OBJECTIVE: Obtain further insights into the concomitant clinical use and safety of rFVIIa and emicizumab. METHODS: The initial individual rFVIIa dose, dosing intervals and cumulative dosing were evaluated in the HAVEN 1, HAVEN 2, and HAVEN 4 trials. All adverse events reported in each of the three trials in patients treated with rFVIIa, including available narratives, were assessed. RESULTS: The vast majority of bleeds occurred in HAVEN 1. When rFVIIa was used to treat a bleeding episode, a 100 ± 20 μg/kg dose was used to initiate treatment in the majority of cases. The dosing interval, as well as cumulative dosing were consistent with prescribing information and current practice. No serious adverse events, no thrombotic microangiopathy cases, or thromboembolic events were assessed to be associated with rFVIIa when used in conjunction with emicizumab prophylaxis in the HAVEN trials. CONCLUSION: rFVIIa use in the context of emicizumab prophylaxis does not change the rFVIIa safety profile as described in the product information.
Authors: Giancarlo Castaman; Cristina Santoro; Antonio Coppola; Maria E Mancuso; Rita C Santoro; Sergio Bernardini; Francesco R Pugliese; Riccardo Lubrano; Maria Golato; Armando Tripodi; Angiola Rocino; Elena Santagostino; Chiara Biasoli; Alessandra Borchiellini; Alberto Catalano; Laura Contino; Antonella Coluccia; Dorina Cultrera; Raimondo De Cristofaro; Giovanni Di Minno; Andrea Fabbri; Massimo Franchini; Gabriella Gamba; Anna Chiara Giuffrida; Paolo Gresele; Adele Giampaolo; Hamisa J Hassan; Matteo Luciani; Emanuela Marchesini; Renato Marino; Maria Gabriella Mazzucconi; Angelo C Molinari; Massimo Morfini; Lucia D Notarangelo; Lucia Peccarisi; Flora Peyvandi; Berardino Pollio; Gianna Franca Rivolta; Maria Pia Ruggieri; Vittorio Sargentini; Mario Schiavoni; Laura Sciacovelli; Maria Luisa Serino; Sergio Siragusa; Annarita Tagliaferri; Sophie Testa; Alberto Tosetto; Stefania Zampogna; Ezio Zanon Journal: Blood Transfus Date: 2019-10-18 Impact factor: 3.443
Authors: Miguel Escobar; Giancarlo Castaman; Santiago Bonanad Boix; Michael Callaghan; Philippe de Moerloose; Jonathan Ducore; Cédric Hermans; Janna Journeycake; Cindy Leissinger; James Luck; Johnny Mahlangu; Wolfgang Miesbach; Ismail Haroon Mitha; Claude Négrier; Doris Quon; Michael Recht; Jean François Schved; Amy D Shapiro; Robert Sidonio; Alok Srivastava; Oleksandra Stasyshyn; Kateryna V Vilchevska; Michael Wang; Guy Young; W Allan Alexander; Ahmad Al-Sabbagh; Daniel Bonzo; Christopher Macie; Thomas A Wilkinson; Craig Kessler Journal: Haemophilia Date: 2021-10-11 Impact factor: 4.263