Safety and efficacy of a new recombinant FVIII formulated with sucrose (rFVIII-FS) in patients with haemophilia A: a long-term, multicentre clinical study in Japan

The recombinant full-length FVIII product Kogenate (R) has been reformulate d using sucrose (rFVIII-FS) instead of human serum albumin as a stabiliser in purification and formulation. The in vivo recovery, haemostatic efficacy , and safety of rFVIII-FS were investigated in 20 previously treated patien ts with severe or moderate haemophilia A for greater than or equal to 24 we eks. In vivo recoveries of 73.5 +/- 16.3%, 78.4 +/- 16.1%, and 82.8 +/- 23. 9% after the initial infusion of 50 IU kg(-1) rFVIII-FS and at weeks 12 and 24, respectively, showed no significant changes over time. A total of 1115 infusions (mean dose 24.1 +/- 8.4 IU kg(-1)) were included in the analysis of haemostatic efficacy. One (80.5%) or two (8.2%) infusions achieved adeq uate haemostasis in 88.7% of all bleeding episodes, and haemostatic efficac y was judged 'excellent' or 'good' in 749 of 764 episodes (98.0%). The haem ostatic efficacy was judged as 'excellent' or 'good' in 924 of 1115 (82.9%) infusions. Twenty-one adverse events were observed in 12 patients in the t otal 1541 infusions included in the safety analysis. Causality with respect to rFVIII-FS could not be ruled out in three events in one HIV-negative pa tient: elevated CD4(%), decreased CD8(%), and elevated CD4/CD8 ratio. No FV III inhibitor development was observed in any patient. ELISA assay testing for antibodies to rFVIII, baby hamster kidney cell (BHK) protein, and murin e IgG were all negative. These results show that rFVIII-FS is a safe and ef fective for long-term treatment of patients with haemophilia A.