The following article features coverage from the European Hematology Association (EHA) 2021 Virtual Congress. Click here to read more of Hematology Advisor‘s conference coverage.

Results of a phase 1 study involving the new anti-von Willebrand factor (VWF) agent BT200 were presented at the European Hematology Association (EHA) 2021 Virtual Congress by Katarina Kovacevic, PhD, of the Medical University of Vienna in Vienna, Austria, and colleagues.

According to Dr Kovacevic, BT200 is a recently designed aptamer that binds to the A1 domain of VWF, inhibiting its binding to platelet glycoprotein Ib and showing a long half-life in nonhuman primates. Aptamers are short, single-stranded molecules of DNA or RNA that have extracellular targets.

Prior research had demonstrated that another anti-VWF aptamer, ARC1779, which also binds to the A1 domain, showed activity in patients who had von Willebrand disease (VWD) type IIb following intravenous infusion. In this study, Dr Kovacevic and colleagues characterized the pharmacokinetic and pharmacodynamic features of BT200, which is an aptamer offering potential subcutaneous administration.

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BT200 was evaluated in the prospective phase 1 BT200-01 trial ( Identifier: NCT04103034), which was a randomized, placebo-controlled first-in-human trial. The trial had 4 components: a single ascending-dose study (88 patients), a multiple ascending-dose study (8 patients), a desmopressin-interaction study (8 patients), and a relative bioavailability study (8 patients).

BT200 was administered either subcutaneously or intravenously. There was a proportional increase in the BT200 plasma concentration as the administered dose increased. With subcutaneous administration, the observed BT200 half-life was 7 to 12 days.

In pharmacodynamic analysis, with increased doses, there was a dose-dependent decrease in free VWF A1 domains, suggesting a dose-dependent inhibition of VWF activity. Dose-dependent signals were also seen in increases of VWF antigen levels and factor VIII activity, beginning with a dosage of 6 mg of BT200 given subcutaneously.

An analysis of patients receiving 12 mg of BT200 subcutaneously suggested that VWF secretion was unaffected by the agent. In this analysis, as free VWF A1 domain levels dropped, thrombin generation, factor VIII activity, and VWF antigen levels showed increases. Additionally, VWF propeptide remained mostly stable.

With multiple doses of BT200, VWF antigen and factor VIII levels also increased as free VWF A1 domains became depleted. When BT200 was combined with desmopressin, there appeared to be an additive effect on factor VIII levels. There were 4 cases of superficial or distal venous thrombosis in the trial.

“BT200 was generally well tolerated but enhanced hemostasis,” Dr Kovacevic stated in her presentation. She continued to explain that the “half-life was quite long, going from 7 to 12 days, supporting once-weekly treatment.” She also suggested the observed increase in factor VIII levels in this study provided an impetus for a phase 2 trial that is now underway with BT200 in hemophilia A and VWD type IIb.

Disclosures: The author(s) have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.

Read more of Cancer Therapy Advisor’s coverage of the EHA 2021 Virtual Congress by visiting the conference page.


Kovacevic K, Jilma B, Quehenberger P, et al. Half-life prolongation of von Willebrand factor: a new therapeutic strategy for haemophilia A and von Willebrand disease. Paper presented at: European Hematology Association 2021 Virtual Congress; June 2021; Abstract S302.