For patients with hemophilia A, BIVV001, a novel fusion protein, may be an effective factor VIII replacement therapy for more sustained factor VIII activity levels, according to research published in The New England Journal of Medicine.
Although factor VIII replacement products have improved the care and quality of life for people with hemophilia A, many products have a short half-life, reducing their protection against bleeding events. Because of the von Willebrand factor (VWF) chaperone effect, recombinant factor VIII replacement products have a half-life of 15 to 19 hours. BIVV001 is designed to protect from rapid plasma clearance and maintain higher sustained factor VIII activity.
A phase 1-2a open label trial evaluated the safety of a single intravenous dose of BIVV001. The study included 16 previously treated men with hemophilia A across 6 sites in the United States and 1 in Japan. Patients received a single intravenous injection of recombinant factor VIII, followed by a washout period of at least 3 days. Then patients received a single injection of BIVV001 in either a lower dose (25 IU/kg of body weight; 7 patients) or a higher dose (65 IU/kg of body weight; 9 patients).
During the 28-day follow-up period, no hypersensitivity or allergic reactions were noted for BIVV001. In addition, none of the patients developed inhibitors to factor VIII, and no clinically relevant changes in VWF activity were detected.
The BIVV001 half-life was 37.6 hours in the lower-dose group and 42.5 hours in the higher-dose group. Mean plasma factor VIII activity was 17% at 4 days after injection and 5% at 7 days in the lower-dose group and 51% at 4 days and 17% at 7 days in the higher-dose group. The half-life for the lower-dose and higher-dose groups with recombinant factor VIII was 9.1 hours and 13.2 hours, respectively.
“High levels of sustained factor VIII activity …. have the potential to allow for better protection against all types of bleeding and a longer interval between administration of the product in patients with severe hemophilia A,” wrote the authors.
Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
Konkle BA, Shapiro AD, Quon DV, et al. BIVV001 fusion protein as factor VIII replacement therapy for hemophilia A. N Engl J Med. 2020;383(11):1018-1027. doi:10.1056/NEJMoa2002699