BIVV001 Increases Half-life of Factor VIII in People with Severe Hemophilia A, Phase 1/2a Trial Shows

A single dose of BIVV001 significantly increased levels of factor VIII for a week in the blood of people with severe hemophilia A, according to early results of a Phase 1/2a study.

The treatment increased the half-life of factor VIII to 44 hours and showed no side effects or development of inhibitors.

The results were presented in an oral session at the 60th Annual Meeting of the American Society of Hematology (ASH) Dec. 1-4 in San Diego, California.

BIVV001, also known as rFVIIIFc-VWF-XTEN, is a new investigational therapy consisting of a factor VIII variant (rFVIII) combined with fragments of three other proteins (Fc, VWF and XTEN).

The fusion molecule is intended to prolong factor VIII’s presence in a patient’s blood longer than current FVIII replacement therapies. The plan is for this therapy to serve as a prophylactic (preventative) treatment that, when administered weekly, prevents bleeding episodes.

In August 2017, the U.S. Food and Drug Administration (FDA) gave BIVV001 orphan drug designation. The therapy was developed by Bioverativ, a Sanofi company, which focuses on the development of therapies for hemophilia and other blood disorders.

Bioverative presented early results of the EXTEN-A Phase 1/2a trial (NTC03205163) evaluating the safety, tolerability, and pharmacokinetics — what happens to a substance inside the body over time —  of a single BIVV001 injection in patients with severe hemophilia A (less than 1% of the normal level of factor VIII in the blood).

Patients received recombinant (made in the lab) factor VIII (rFVIII) and, after a wash-out period, a single dose of BIVV001 at either 25 IU/kg (six patients) or 65 IU/kg (two patients). The patients ranged from 18 to 65 years old.

“Longer prophylactic dosing intervals that offer maximum overall protection from bleeds are still an unmet need for people with severe hemophilia A,” Barbara A. Konkle, MD, associate chief scientific officer at Bloodworks Northwest and professor of medicine/hematology at the University of Washington, said in a press release.

The 65 IU/kg dose of BIVV001 extended the half-life of factor VIII to 44 hours; the observed half-life of a similar dose of rFVIII was 17 hours.

“In these initial results, a single 65 IU/kg dose of BIVV001 resulted in a much greater half-life than traditional recombinant factor therapy, achieving an average factor activity level of 18.5% at seven days post-infusion,” Konkle said.

The 25 IU/kg dose extended the half-life of factor VIII to 38 hours, a significant increase over the 9-hour half-life of rFVIII at a similar dose. The levels of factor VIII in patients’ blood were over 5% seven days after injection.

“We are very encouraged by these results, which suggest that BIVV001 has the potential to markedly improve the treatment paradigm for patients and physicians, and we look forward to learning more as the trial continues,” said Tim Harris, PhD, DSc, executive vice president of research and development at Bioverativ.