Engineered Clotting Protein Stops Bleeding in Most Common Inherited Bleeding Disorder
First-of-its-kind protein shown effective in severe von Willebrand disease
Published on: August 03, 2015
(WASHINGTON, August 3, 2015) – The first
protein engineered to help control bleeding episodes in patients with severe
von Willebrand disease (vW disease) has been shown to be safe and effective,
according to results of a Phase III trial. Study data
were published online today in Blood,
the Journal of the American Society of
When a blood vessel becomes damaged, a
protein called von Willebrand factor (vWF) helps stop bleeding by guiding
clot-forming platelets to the injury. vWF serves as the “glue” that helps
platelets stick to a wound. Approximately 1 percent of the general population
lacks a sufficient quantity of fully functioning vWF.
This results in vW disease, which is characterized by excessive and often
While some patients with vW disease have mild
or no symptoms, others have a more severe form of the disease that can be
difficult to treat. Until recently, bleeding episodes in individuals with
severe vW disease were treated with an infusion of purified vWF, which
circulates in combination with factor VIII (FVIII), another clotting protein.
While this treatment approach is often effective, the major disadvantage is
that vWF is purified from plasma, which has the potential to introduce patients
to blood-borne contaminants.
Seeking a more targeted vW disease treatment
without the disadvantages associated with blood-derived products, investigators
engineered a cell line that expresses the vWF gene to create a
consistent, highly active recombinant vWF (rvWF). After preliminary studies,
investigators enrolled 49 patients who had received vWF concentrate treatment
for at least one severe vW disease-related bleed within the last 12 months in a
Phase III trial to evaluate the efficacy and safety of rVWF. Patients were
randomly assigned to one of four treatment arms. In order to observe rvWF’s
activity at varying doses and in different treatment scenarios, investigators
gave patients 50 IU/kg or 80 IU/kg body weight either alone or with engineered
FVIII (rFVIII). The majority of patients in the study received as-needed
treatment of 40-60 IU rvWF/kg for regular bleeding episodes and up to 80 IU/kg
for major bleeds.
Confirming the results of past studies, the
activity of rvWF remained the same with and without rFVIII. Investigators
observed that patients who received rvWF alone experienced a rapid increase in
their naturally produced FVIII. In fact, within six hours after an infusion,
patients had produced enough of the protein for proper clotting. This response
was sustained through 72 hours post infusion, suggesting that patients who
receive rvWF are not likely to require additional rFVIII infusions.
vW disease specialists also rated the
recombinant product’s ability to control bleeds on a scale of “excellent” to
“no response.” After 12 months, the specialists had treated 192 bleeding
episodes in 22 patients with severe vW disease and rated rvWF as “excellent” (96.9%)
or “good” (3.1%) in controlling bleeding. In addition, more than 80 percent of
bleeds were resolved with a single rvWF infusion.
“These efficacy and safety data of
recombinant vWF represent a major advance in our quest to develop an optimal
treatment for people living with vW disease,” said lead investigator Bruce
Ewenstein, MD, PhD, of Baxalta, Inc. “As this product is specifically designed
to be administered without factor VIII, it will allow physicians to dose vWF
and FVIII separately and precisely based on the needs of each individual
patient. This treatment strategy has the potential to become the standard of
care for patients with severe von Willebrand disease.”
Blood (www.bloodjournal.org), the
most cited peer-reviewed publication in the field of hematology, is available
weekly in print and online. Blood is the official journal of the
American Society of Hematology (ASH) (www.hematology.org),
the world’s largest professional society concerned with the causes and
treatment of blood disorders.
ASH’s mission is to further the
understanding, diagnosis, treatment, and prevention of disorders affecting
blood, bone marrow, and the immunologic, hemostatic, and vascular systems by
promoting research, clinical care, education, training, and advocacy in
blood® is a registered trademark of the
American Society of Hematology.
 “Von Willebrand Disease (VWD).”
Centers for Disease Control and Prevention. Accessed from: http://www.cdc.gov/ncbddd/vwd/data.html#ref.
Amanda Szabo, American Society of Hematology
back to top