title: Efficacy and safety of prophylaxis with once-weekly BAY 79-4980 compared with thrice-weekly rFVIII-FS in haemophilia A patients. A randomised, active-controlled, double-blind study.
abstract: The benefits of prophylaxis of haemophilia A patients regarding joint health and quality-of-life are well established. However, adherence to an up to every-other-day infusion regimen is a barrier to widespread adoption of prophylaxis. BAY 79-4980 is an investigational drug consisting of rFVIII-FS (sucrose-formulated recombinant FVIII) reconstituted with liposome solvent. Previous clinical studies showed extended protection from bleeding after a single injection of BAY 79-4980 (13.3 ± 6.2 days) compared with rFVIII-FS (7.2 ± 1.7 days). The effect of once-a-week prophylaxis with BAY 79-4980 (35 IU/kg) compared with three times-per-week rFVIII-FS (25 IU/kg) in previously treated, severe haemophilia A patients was evaluated in a 52-week, double-blind, two-arm, randomised, controlled study. The primary and secondary endpoints were protection from total bleeds and joint bleeds, respectively. Short- and long-term safety and tolerability of BAY 79-4980 including effects on lipid levels were assessed. A total of 139 and 131 subjects were evaluable for safety and efficacy analyses, respectively. A large difference in efficacy between treatment groups was observed with 72.1% (49/68) in the rFVIII-FS control group demonstrating <9 bleeds/year compared with 38.1% (24/63) of BAY 79-4980-treated subjects. A similar difference was seen in annualised joint bleeds, with 43 subjects (63.2%) in the control group demonstrating <5 joint bleeds/year compared with 24 subjects (38.1%) treated with BAY 79-4980. The distribution of bleeds seven days post-prophylactic treatment with BAY 79-4980 showed that 61% of bleeds occurred after day 4 post dosing. There were no safety concerns identified. The investigational treatment arm was prematurely discontinued due to failure to achieve the primary endpoint.
authors.affiliation: Division of Hematology/Oncology, School of Medicine, University of California at Davis, Davis, California, USA. jspowell@ucdavis.edu
authors.forename: Jerry
authors.initials: J
authors.lastname: Powell
authors.forename: Uri
authors.initials: U
authors.lastname: Martinowitz
authors.forename: Jerzy
authors.initials: J
authors.lastname: Windyga
authors.forename: Giovanni
authors.initials: G
authors.lastname: Di Minno
authors.forename: Andrzej
authors.initials: A
authors.lastname: Hellmann
authors.forename: Ingrid
authors.initials: I
authors.lastname: Pabinger
authors.forename: Monika
authors.initials: M
authors.lastname: Maas Enriquez
authors.forename: Lawrence
authors.initials: L
authors.lastname: Schwartz
authors.forename: Jørgen
authors.initials: J
authors.lastname: Ingerslev
mesh_terms: D000293:Adolescent; D000328:Adult; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005169:Factor VIII / Q000008:administration & dosage* / Q000009:adverse effects; D006467:Hemophilia A / Q000188:drug therapy*; D006470:Hemorrhage / Q000517:prevention & control; D006801:Humans; D008081:Liposomes / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage; D012997:Solvents; D013395:Sucrose / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D003692:Delayed-Action Preparations; D008081:Liposomes; D012997:Solvents; C438308:recombinant FVIII, sugar formulated; D011092:Polyethylene Glycols; D013395:Sucrose; D005169:Factor VIII