Bioverativ developed BIVV001 to extend protection from bleeds in hemophilia type A patients, with preventive (prophylaxis) dosing of once weekly or longer. Sanofi acquired Bioverativ in 2018 and is continuing the development of the treatment.
How does BIVV001 work?
BIVV001 is based on 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. The goal is to potentially extend its lifetime in the body’s circulation. It is the first molecule of its kind to fuse together four different proteins: FVIII, VWF, XTEN, and Fc. That fusion leads to more stability and a longer half-life than was possible with existing long-acting FVIII therapies.
BIVV001 in preclinical studies
In preclinical studies, BIVV001 showed similar in vivo or in-the-body effectiveness compared with rFVIII. It also extended the half-life of FVIII in mouse models of hemophilia type A to two times beyond that achieved with Fc fusion technology, and four-fold beyond conventional FVIII alone. The half-life of intravenously (into-the-vein) administered BIVV001 was about 37 hours. This was more than four times longer than that of conventional FVIII.
In addition, animals that received a low dose (25 IU/kg) of BIVV001 retained 5% of normal FVIII activity after 120 hours. This suggested the potential for full protection from spontaneous bleeding in this animal model.
When the treatment was delivered under the skin, the bioavailability (availability in the plasma) of BIVV001 was 20%. This was a significant increase compared with the less than 1% bioavailability of conventional FVIII. After 24 hours of under-the-skin administration of BIVV001, plasma FVIII levels were equal to or greater than those attained with conventional FVIII delivered intravenously, or into the vein, at the same dose.
BIVV001 in clinical trials
An open-label, dose-escalation Phase 1/2a study (NCT03205163) investigated the safety, tolerability, and pharmacokinetics (movement in the body) of a single dose of BIVV001. The therapy was injected into the bloodstream of adults with severe hemophilia type A who had received previous treatment. A total of 12 men received a single intravenous dose of either 25 IU/kg (25 IU per kg of body weight) or 65 IU/kg of treatment.
After at least three days, the patients received another injection at the same dosage. The results of the study, published in The New England Journal of Medicine, showed that BIVV001 lasted in the body three to four times as long as just rFVIII, suggesting that weekly injections may suffice for treatment.
A Phase 3 open-label, non-randomized clinical trial (NCT04161495), called XTEND-1, is currently recruiting an estimated 150 patients, ages 12 and older, who have previously received treatment for hemophilia A. In the trial, being conducted at locations in California, Nevada, and Washington, researchers place participants into two different treatment arms. One group of patients receives a weekly prophylactic dose of 50 IU/kg of treatment for 52 weeks. The second group gets on-demand injections of 50 IU/kg of treatment for 26 weeks. That group will then switch to weekly prophylaxis for another 26 weeks.
The study is investigating the annualized bleeding rate for both groups of patients. It also will monitor the treatment’s long-term safety. Researchers estimate the study will be completed in December 2021.
The FDA granted BIVV001 orphan drug designation in August 2017 and the European Commission followed suit in June 2019.
Last updated: Oct. 1, 2020
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