title: BAY 81-8973 safety and efficacy for prophylaxis and treatment of bleeds in previously treated children with severe haemophilia A: results of the LEOPOLD Kids Trial.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.affiliation: Department of Clinical Sciences Lund-Pediatrics, Malmö Centre for Thrombosis and Haemostasis, Skåne University Hospital, Lund University, Malmö, Sweden.
authors.forename: R
authors.initials: R
authors.lastname: Ljung
authors.affiliation: Chaim Sheba Medical Center, The Israeli National Hemophilia Center, The Sackler Medical School, Tel Aviv University, Tel-Hashomer, Israel.
authors.forename: G
authors.initials: G
authors.lastname: Kenet
authors.affiliation: Angelo Bianchi Bonomi Hemophilia and Thrombosis Centre, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: M E
authors.initials: ME
authors.lastname: Mancuso
authors.affiliation: MHAT Sveta Marina, Clinic of Pediatric Hematology and Oncology, Varna, Bulgaria.
authors.forename: V
authors.initials: V
authors.lastname: Kaleva
authors.affiliation: SC Sanador SRL, Bucharest, Romania.
authors.forename: L
authors.initials: L
authors.lastname: Rusen
authors.affiliation: Bayer Pharma AG, Berlin, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Tseneklidou-Stoeter
authors.affiliation: Bayer HealthCare Pharmaceuticals, Whippany, NJ, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Michaels
authors.affiliation: Bayer HealthCare Pharmaceuticals, Whippany, NJ, USA.
authors.forename: A
authors.initials: A
authors.lastname: Shah
authors.affiliation: Bayer HealthCare Pharmaceuticals, Whippany, NJ, USA.
authors.forename: W
authors.initials: W
authors.lastname: Hong
authors.affiliation: Bayer Pharma AG, Wuppertal, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Maas Enriquez
mesh_terms: D019540:Area Under Curve; D002648:Child; D002675:Child, Preschool; D003029:Coagulants / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005169:Factor VIII / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006207:Half-Life; D006467:Hemophilia A / Q000188:drug therapy* / Q000473:pathology; D006470:Hemorrhage / Q000517:prevention & control; D006801:Humans; D007223:Infant; D008297:Male; D012372:ROC Curve; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D003029:Coagulants; C078147:F8 protein, human; D005169:Factor VIII
keywords: children; clinical trial; factor VIII; haemophilia A; prophylaxis