BIVV001 Extends Lifetime of Hemophilia A Replacement Therapy, Early Trial Data Shows

José Lopes, PhD avatar

by José Lopes, PhD |

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AMT-180 preclinical study

Preliminary results of a Phase 1/2a trial of the hemophilia A experimental treatment BIVV001 show a significant extension of replacement therapy lifetime in the blood, Bioverativ announced.

The ongoing, and still recruiting, open-label, multicenter EXTEN-A study (NCT03205163) is evaluating the safety, tolerability, and pharmacokinetics of a single intravenous injection of low- and high-dose BIVV001 in adult hemophilia A patients ages 18-65. Pharmacokinetics refers to the study of drug absorption, distribution, metabolism, and excretion in the body.

Factor replacement therapy for hemophilia A provides the normal version of a clotting protein called factor VIII (FVIII), which is defective or missing in patients.

BIVV001 (rFVIIIFc-VWF-XTEN) combines a region of a blood-clotting protein called von Willebrand factor and a molecule called XTEN to extend the lifetime of recombinant (lab-made) FVIII in circulation.

Bioverativ says BIVV001 is the only treatment candidate able to overcome the von Willebrand factor ceiling, which is thought to limit the half-life – the time required for a 50% reduction in a compound’s blood concentration – of current therapies.

The potential therapy is intended to provide once-weekly or less prophylactic (preventive) dosing for hemophilia A patients.

The findings, presented at the World Federation of Hemophilia (WFH) 2018 World Congress, held recently in Glasgow, Scotland, revealed that the low dose (25 IU/kg) BIVV001 prolonged the FVIII half-life to 37 hours in four men after a washout period.

This represents a significant improvement over the 13 hours seen with current recombinant FVIII therapy.

As of the April 20 analysis cut-off date, the data also showed a high factor activity – 13.0% at five days and 5.6% at seven days after infusion with BIVV001.

This parameter refers to the amount of FVIII in the blood and correlates with the severity of symptoms. While patients with severe hemophilia have factor levels lower than 1%, moderate hemophilia patients have 1-5%, and those with mild disease have 6-49%.

Treatment with BIVV001 was generally well-tolerated, with no development of inhibitors. The company is now evaluating a twice-monthly dosing regimen.

“For decades, scientists have been trying to overcome the von Willebrand factor ceiling, which imposes a limit on the half-life of factor VIII, and these data demonstrate that BIVV001 has finally broken through that ceiling,” Joachim Fruebis, senior vice president of development at Bioverativ, said in a press release.

“Importantly for the hemophilia community, the factor levels seen in this study are unparalleled in hemophilia A, and we are excited about the potential for BIVV001 to transform the treatment paradigm for patients and physicians,” he said.

The EXTEN-A trial is currently enrolling male participants ages 18-65 in the U.S. and Japan. For more information, please click here.

According to Bioverativ, BIVV001 has the potential to offer protection across all treatment scenarios including acute bleeds, perioperative care, emergency situations, and prophylactic use. Besides its benefits against bleeding, replacement therapy may also help improve patients’ joint and bone health.

In 2017, the U.S. Food and Drug Administration granted BIVV001 orphan drug atatus and accepted Bioverativ’s investigational new drug (IND) application for this investigational product.