title: Efficacy and safety of BAY 81-8973, a full-length recombinant factor VIII: results from the LEOPOLD I trial.
abstract: BACKGROUND
  BAY 81-8973 (Kovaltry(®) ) is a full-length, unmodified recombinant human factor VIII (FVIII) with the same amino acid sequence as sucrose-formulated recombinant FVIII and is produced using additional advanced manufacturing technologies.
  
  
  OBJECTIVE
  To demonstrate efficacy and safety of BAY 81-8973 for treatment of bleeds and as prophylaxis based on two different potency assignments.
  
  
  METHODS
  In LEOPOLD I (ClinicalTrials.gov identifier, NCT01029340), males aged 12-65 years with severe haemophilia A and ≥150 exposure days received BAY 81-8973 20-50 IU kg(-1) two or three times per week for 12 months. Potency was based on chromogenic substrate assay per European Pharmacopoeia and label adjusted to mimic one-stage assay potency. Patients were randomized for potency sequence and crossed over potency groups after 6 months, followed by an optional 12-month extension. Primary efficacy endpoint was annualized bleeding rate (ABR). Patients also received BAY 81-8973 during major surgeries.
  
  
  RESULTS
  Sixty-two patients received BAY 81-8973 prophylaxis and were included in the analysis. Median ABR was 1.0 (quartile 1, 0; quartile 3, 5.1) without clinically relevant differences between potency periods. Median ABR was similar for twice-weekly vs. three times-weekly dosing (1.0 vs. 2.0). Haemostasis was maintained during 12 major surgeries. Treatment-related adverse event (AE) incidence was ≤7% overall; no patient developed inhibitors. One patient with risk factors for cardiovascular disease developed a myocardial infarction.
  
  
  CONCLUSIONS
  BAY 81-8973 was efficacious in preventing and treating bleeding episodes, irrespective of the potency assignment method, with few treatment-related AEs. Caution should be used when treating older patients with cardiovascular risk factors.
authors.affiliation: Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. kapil.saxena@bayer.com.
authors.forename: K
authors.initials: K
authors.lastname: Saxena
authors.affiliation: National Haemophilia Centre, Chaim Sheba Medical Centre, Tel-Hashomer, Israel.
authors.forename: S
authors.initials: S
authors.lastname: Lalezari
authors.affiliation: University Clinic Bonn, Bonn, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Oldenburg
authors.affiliation: Bayer Pharma AG, Berlin, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Tseneklidou-Stoeter
authors.affiliation: Bayer Pharma AG, Wuppertal, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Beckmann
authors.affiliation: Bayer Inc., Toronto, ON, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Yoon
authors.affiliation: Bayer Pharma AG, Wuppertal, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Maas Enriquez
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D003029:Coagulants / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; 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; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000209:etiology; D009985:Orthopedics; D012307:Risk Factors; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D003029:Coagulants; C078147:F8 protein, human; D005169:Factor VIII
keywords: clinical studies; efficacy; factor VIII; haemophilia A; prophylaxis; surgery