R Ljung1, G Kenet2, M E Mancuso3, V Kaleva4, L Rusen5, D Tseneklidou-Stoeter6, L A Michaels7, A Shah7, W Hong7, M Maas Enriquez8. 1. Department of Clinical Sciences Lund-Pediatrics, Malmö Centre for Thrombosis and Haemostasis, Skåne University Hospital, Lund University, Malmö, Sweden. 2. Chaim Sheba Medical Center, The Israeli National Hemophilia Center, The Sackler Medical School, Tel Aviv University, Tel-Hashomer, Israel. 3. Angelo Bianchi Bonomi Hemophilia and Thrombosis Centre, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, Milan, Italy. 4. MHAT Sveta Marina, Clinic of Pediatric Hematology and Oncology, Varna, Bulgaria. 5. SC Sanador SRL, Bucharest, Romania. 6. Bayer Pharma AG, Berlin, Germany. 7. Bayer HealthCare Pharmaceuticals, Whippany, NJ, USA. 8. Bayer Pharma AG, Wuppertal, Germany.
Abstract
INTRODUCTION: BAY 81-8973, a full-length, unmodified, recombinant factor VIII (FVIII) in development for treatment of haemophilia A, has the same primary amino acid sequence as Bayer's sucrose-formulated recombinant FVIII but is produced with more advanced manufacturing technologies. AIM: To demonstrate safety and efficacy of BAY 81-8973 for prophylaxis and treatment of bleeds in previously treated children. METHODS: In this phase III, multicentre, open-label, nonrandomized study, boys aged ≤12 years with severe haemophilia A and ≥50 exposure days (EDs) to FVIII products received prophylaxis with BAY 81-8973 25-50 IU kg(-1) ≥2 times weekly for ≥50 EDs. The efficacy endpoint was annualized number of total bleeds. Adverse events (AEs) and immunogenicity were assessed. RESULTS: Fifty-one patients were treated (age: <6 years, n = 25; 6-<12 years, n = 26) with a 2× per week (43%) or >2× per week (57%) regimen at study start. Median [quartile 1; quartile 3 (Q1; Q3)] annualized number of bleeds for the combined age groups was 1.90 (0; 6.02) for total bleeds, 0 (0; 2.01) for joint bleeds and 0 (0; 0) for spontaneous bleeds. Median (Q1; Q3) annualized number of total bleeds within 48 h of previous prophylaxis infusion was 1.88 (0; 3.97) for children aged <6 years and 0 (0; 1.96) for children aged 6-<12 years. No drug-related serious AEs or inhibitors were reported. CONCLUSIONS: Prophylaxis with BAY 81-8973 using individualized prophylaxis regimens of 2× per week, 3× per week and every-other-day infusions was efficacious in prevention and treatment of bleeds in children with severe haemophilia A. Treatment with BAY 81-8973 was well tolerated.
INTRODUCTION:BAY 81-8973, a full-length, unmodified, recombinant factor VIII (FVIII) in development for treatment of haemophilia A, has the same primary amino acid sequence as Bayer's sucrose-formulated recombinant FVIII but is produced with more advanced manufacturing technologies. AIM: To demonstrate safety and efficacy of BAY 81-8973 for prophylaxis and treatment of bleeds in previously treated children. METHODS: In this phase III, multicentre, open-label, nonrandomized study, boys aged ≤12 years with severe haemophilia A and ≥50 exposure days (EDs) to FVIII products received prophylaxis with BAY 81-8973 25-50 IU kg(-1) ≥2 times weekly for ≥50 EDs. The efficacy endpoint was annualized number of total bleeds. Adverse events (AEs) and immunogenicity were assessed. RESULTS: Fifty-one patients were treated (age: <6 years, n = 25; 6-<12 years, n = 26) with a 2× per week (43%) or >2× per week (57%) regimen at study start. Median [quartile 1; quartile 3 (Q1; Q3)] annualized number of bleeds for the combined age groups was 1.90 (0; 6.02) for total bleeds, 0 (0; 2.01) for joint bleeds and 0 (0; 0) for spontaneous bleeds. Median (Q1; Q3) annualized number of total bleeds within 48 h of previous prophylaxis infusion was 1.88 (0; 3.97) for children aged <6 years and 0 (0; 1.96) for children aged 6-<12 years. No drug-related serious AEs or inhibitors were reported. CONCLUSIONS: Prophylaxis with BAY 81-8973 using individualized prophylaxis regimens of 2× per week, 3× per week and every-other-day infusions was efficacious in prevention and treatment of bleeds in children with severe haemophilia A. Treatment with BAY 81-8973 was well tolerated.
Authors: Cristina Santoro; Beng Fuh; Phu Quoc Le; Philip Maes; Rubén Berrueco; Eva Maria Mingot-Castellano; Sylvia von Mackensen; Alexander Solms; Michael Wang Journal: Eur J Haematol Date: 2020-04-23 Impact factor: 2.997
Authors: João A Abrantes; Alexander Solms; Dirk Garmann; Elisabet I Nielsen; Siv Jönsson; Mats O Karlsson Journal: Haematologica Date: 2019-08-01 Impact factor: 9.941
Authors: João A Abrantes; Alexander Solms; Dirk Garmann; Elisabet I Nielsen; Siv Jönsson; Mats O Karlsson Journal: CPT Pharmacometrics Syst Pharmacol Date: 2019-10-30