A novel therapeutic approach using aptamers – short single strands of DNA or RNA designed to selectively bind to a target – shows promise for treating von Willebrand Disease (VWD), and other congenital bleed disorders such as hemophilia A, investigators say.
In a proof-of-concept study using healthy volunteers, the experimental anti–von Willebrand factor (VWF) molecule BT200 appeared to decrease clearance of VWF and resulted in a twofold increase in endogenous levels of VWF and factor VIII at low doses.
BT200 is currently being explored in a phase 2 trial in patients with hemophilia A and VWD type 2B, Katarina Kovacevic, MPharm, from the Medical University of Vienna, reported at the European Hematology Association annual congress.
“We expect to see a half-life increase of 2 to 4 times of factor VIII products, which will allow us to have a longer time between treatments,” she said in an oral abstract presentation (Abstract S302).
Lab-made nucleotide strings
Aptamers are sometimes call “chemical antibodies” because of their high affinity and high specificity for extracellular targets, Dr. Kovacevic said. Unlike conventional humanized or human-derived antibodies, however, they are nonimmunogenic and are less costly to manufacture.
In a previous study from her center, a different anti-VWF aptamer labeled ARC1779 increased plasma levels of VWF, factor VIII, and platelet counts in patients with VWD type 2B.
However, the drug was inconvenient to use, requiring 72-hour infusions, she noted.
In a study published in Feb. 4, 2021 in Scientific Reports, Dr. Kovacevic and colleagues reported that BT200 blocks VWF and platelet function in patients with ischemic strokes, even in the presence of high levels of VWF in patients with left carotid artery atherosclerotic strokes.
The ability of the molecule to block VWF platelet binding may explain how the anti-VWF agent actually results in higher circulating levels of VWF, which also carries factor VIII, said Veronica H. Flood, MD, a VWD specialist at Children’s Hospital of Wisconsin and associate professor at the Medical College of Wisconsin in Milwaukee.
“It might inhibit clearance of the von Willebrand factor, so it’s almost like this was an incidental side effect,” she said in an interview. “Incidentally, this happens to also give you higher levels of the von Willebrand factor and the factor VIII, and with a longer half-life than anything we currently have, so it’s a super-creative strategy,” she said.
Dr. Flood was not involved in the study.