title: Sucrose formulated recombinant human antihemophilic factor VIII is safe and efficacious for treatment of hemophilia A in home therapy--International Kogenate-FS Study Group.
abstract: To add an increased level of safety to antihemophilic factor replacement therapy, a full-length, recombinant Factor VIII (rFVIII) product has been developed without human-derived plasma proteins during purification and formulation and using an additional solvent/detergent viral inactivation step. This first clinical trial of a sucrose-formulated full-length rFVIII (rFVIII-FS) was conducted in previously treated patients (> or = 100 prior exposure days) with severe (<2% FVIII) hemophilia A in North America (NA) and Europe (EU). Pharmacokinetic profiles for rFVIII-FS were compared with those of currently licensed rFVIII product (Kogenate) in 35 patients. Safety and efficacy during home therapy were evaluated in 71 patients. The new formulation displayed a pharmacokinetic profile similar to that of rFVIII. Patients on home therapy received a cumulative total of 11,867 exposure days, 12,546 infusions, and 22,443,694 IU of rFVIII-FS. Of 2585 bleeds, 93.5% were treated with 1-2 infusions and 80.5% of responses were rated as excellent or good. No evidence of de novo inhibitor formation was observed. Only 0.27% of infusions were associated with any drug-related adverse event. Except for an episode of intermittent chest pain with palpitations which ceased after treatment with analgesics, associated adverse events were mild or moderate. Overall, rFVIII-FS provided excellent hemostatic control, was well-tolerated, and caused no significant adverse effects, thus demonstrating safety and efficacy for treatment of bleeds in patients with hemophilia A.
authors.affiliation: Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA. tabshir@emory.edu
authors.forename: T C
authors.initials: TC
authors.lastname: Abshire
authors.forename: H H
authors.initials: HH
authors.lastname: Brackmann
authors.forename: I
authors.initials: I
authors.lastname: Scharrer
authors.forename: K
authors.initials: K
authors.lastname: Hoots
authors.forename: C
authors.initials: C
authors.lastname: Gazengel
authors.forename: J S
authors.initials: JS
authors.lastname: Powell
authors.forename: E
authors.initials: E
authors.lastname: Gorina
authors.forename: E
authors.initials: E
authors.lastname: Kellermann
authors.forename: E
authors.initials: E
authors.lastname: Vosburgh
mesh_terms: D000293:Adolescent; D000328:Adult; D000906:Antibodies / Q000097:blood; D002648:Child; D018592:Cross-Over Studies; D004339:Drug Compounding; D004341:Drug Evaluation; D005169:Factor VIII / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D006467:Hemophilia A / Q000150:complications / Q000188:drug therapy; D006470:Hemorrhage / Q000188:drug therapy / Q000517:prevention & control; D018718:Home Infusion Therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D010314:Partial Thromboplastin Time; D017060:Patient Satisfaction; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D013395:Sucrose; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000906:Antibodies; D011994:Recombinant Proteins; D013395:Sucrose; C078147:F8 protein, human; D005169:Factor VIII