BACKGROUND: Factor VIII replacement products have improved the care of patients 
with hemophilia A, but the short half-life of these products affects the 
patients' quality of life. The half-life of recombinant factor VIII ranges from 
15 to 19 hours because of the von Willebrand factor chaperone effect. BIVV001 
(rFVIIIFc-VWF-XTEN) is a novel fusion protein designed to overcome this 
half-life ceiling and maintain high sustained factor VIII activity levels. Data 
are lacking on the safety and pharmacokinetics of single-dose BIVV001.
METHODS: In this phase 1-2a open-label trial, we consecutively assigned 16 
previously treated men (18 to 65 years of age) with severe hemophilia A (factor 
VIII activity, <1%) to receive a single intravenous injection of recombinant 
factor VIII at a dose of 25 IU per kilogram of body weight (lower-dose group) or 
65 IU per kilogram (higher-dose group). This injection was followed by a washout 
period of at least 3 days. The patients then received a single intravenous 
injection of BIVV001 at the same corresponding dose of either 25 IU or 65 IU per 
kilogram. Adverse events and pharmacokinetic measurements were assessed.
RESULTS: No inhibitors to factor VIII were detected and no hypersensitivity or 
anaphylaxis events were reported up to 28 days after the injection of 
single-dose BIVV001. The geometric mean half-life of BIVV001 was three to four 
times as long as that of recombinant factor VIII (37.6 hours vs. 9.1 hours in 
the lower-dose group and 42.5 vs. 13.2 hours in the higher-dose group); the area 
under the curve (AUC) for product exposure was six to seven times as great in 
the two dose groups (4470 hours vs. 638 hours × IU per deciliter in the 
lower-dose group and 12,800 hours vs. 1960 hours × IU per deciliter in the 
higher-dose group). After the injection of BIVV001 in the higher-dose group, the 
mean factor VIII level was in the normal range (≥51%) for 4 days and 17% at day 
7, which suggested the possibility of a weekly interval between treatments.
CONCLUSIONS: In a small, early-phase study involving men with severe hemophilia 
A, a single intravenous injection of BIVV001 resulted in high sustained factor 
VIII activity levels, with a half-life that was up to four times the half-life 
associated with recombinant factor VIII, an increase that could signal a new 
class of factor VIII replacement therapy with a weekly treatment interval. No 
safety concerns were reported during the 28-day period after administration. 
(Funded by Sanofi and Sobi; ClinicalTrials.gov number, NCT03205163.).