BIVV001, also known as rFVIIIFc-VWF-XTEN, is a novel investigational factor VIII (FVIII) therapy, developed by Bioverativ. It is designed to extend protection from bleeds in patients with hemophilia type A with prophylaxis dosing of once weekly or longer.

In June 2017, the U.S. Food and Drug Administration (FDA) accepted the company’s investigational new drug (IND) application for BIVV001 based on encouraging results from preclinical studies.

How BIVV001 works

BIVV001 is based on a Fc fusion technology made by adding a region of a blood-clotting protein called the von Willebrand factor (VWF) and a polypeptide called XTEN to the recombinant FVIII-Fc fusion, to potentially extend its lifetime in the circulation. It is the first molecule of its kind to fuse four different proteins together – FVIII, VWF, XTEN, and Fc — leading to more stability and longer half-life than achieved with current long-acting FVIII therapies.

BIVV001 in preclinical studies

In preclinical studies, BIVV001 showed similar in vivo effectiveness compared to rFVIII, and extended the half-life of FVIII in mouse models of hemophilia type A to two-fold beyond that achieved with Fc fusion technology, and four-fold beyond conventional FVIII alone. The half-life of intravenously administered BIVV001 was about 37 hours, which is more than four-fold longer than that of conventional FVIII. In addition, animals that received a low dose (25 IU/kg) of BIVV001 retained 5 percent of normal FVIII activity after 120 hours, which suggested the potential for full protection from spontaneous bleeding in this animal model.

When the drug was delivered under the skin, the bioavailability (availability in blood plasma) of BIVV001 was 20 percent, a significant increase compared to less than 1 percent bioavailability with conventional FVIII. After 24 hours, under-the-skin administration of BIVV001, plasma FVIII levels that were equal to or greater than those attained with conventional FVIII delivered intravenously at the same dose, were achieved.

BIVV001 in clinical trials

An open-label, dose-escalation Phase 1/2a study (NCT03205163) was initiated to determine the safety, tolerability, and pharmacokinetics (movement in the body) of a single dose of BIVV001, which is injected into the bloodstream of adult patients with severe hemophilia type A who have been previously treated. The study is currently recruiting participants at four sites in the U.S. and is expected to be completed by 2018. 

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