2026 marks the 100th anniversary of the discovery of von Willebrand disease. In his landmark paper, Finnish physician Erik von Willebrand first described an inheritable bleeding disorder in a 5-year-old girl who was part of a large family in which several children had died from severe bleeding.
In the century since it was discovered, von Willebrand disease (VWD) has gone from a mysterious “pseudohemophilia” to the most commonly recognized inherited bleeding disorder in the world, affecting up to 1% of the population.
Treatment for VWD has evolved from basic blood transfusions to sophisticated therapies, including the introduction of desmopressin in the 1970s and the development of plasma-derived and recombinant von Willebrand factor (VWF) concentrates.
It’s an exciting time for VWD research, says Robert Sidonio Jr., M.D., M.Sc., director of hemostasis and thrombosis clinical operations at the Aflac Cancer and Blood Disorders Center of Children’s Healthcare of Atlanta.
“Hemophilia is still a problem, but there are so many good hemophilia drugs currently and still some that are coming to the market soon that a lot of companies are now saying, ‘OK, where’s the unmet need?’ And we’re telling them it’s in von Willebrand disease,” Sidonio says.
Here’s a look at the latest advances in VWD treatment, including what’s in the pipeline:
Expanded Indications for VWF Concentrates
Sidonio says one of the most important treatment advances for VWD in recent years involves expanded indications for factor replacement products so that they can now be used for prophylaxis instead of just to treat bleeds after they occur.
In 2023, the human plasma-derived von Willebrand factor (VWF)/factor VIII replacement product Wilate received Food and Drug Administration (FDA) approval for prophylaxis in children and adults with VWD who have recurrent bleeding. In 2025, the FDA expanded the indication of the recombinant VWF replacement therapy Vonvendi to include prophylaxis use to reduce the frequency of bleeding episodes in adults with all types of VWD.
Previously, although doctors would sometimes prescribe these medications “off label” for prophylaxis, patients and families would run into problems getting the medication covered by insurance.
“Because these products did not have the prophylaxis indication on the label, families were often frustrated when insurance denied prescriptions,” Sidonio says. “Now, thanks to the clinical trials that secured these indications, it frees up the nurses from having to do all kinds of prior authorizations and paperwork, and it’s made it much easier for patients with VWD and repeated bleeding who need prophylaxis to get access.”
Pipeline of Subcutaneous Prophylaxis Treatments for Von Willebrand Disease
Just as many of the newest medications for hemophilia have shifted from IV infusions to subcutaneous injections, the same is happening with drugs that are currently being developed for VWD.
Sidonio says one of the most promising medicines that is furthest along in the pipeline is VGA039, a subcutaneous therapy being developed by Star Therapeutics. “Phase 3 trials, which are the final phase to get FDA approval, have just started, but the data looks very promising,” he says. In the phase 2 trials, patients who were having daily nosebleeds had a significant reduction in their bleeding.
“The approval is still a few years away, depending on how quickly we can enroll patients in the trials,” he adds.
Other subcutaneous candidates that are still in earlier phases of development include HMB-002 from Hemab Therapeutics, as well as potential VWD drugs from Alnylam Pharmaceuticals, Tangram Therapeutics, and SeraGene Therapeutics.
“With most of these drugs, they’re looking at an every two-to-four-week injection period, so this is obviously a huge administrative burden reduction, compared with giving an IV infusion two to three times a week,” Sidonio says.
What’s especially encouraging, he says, is that there are so many drugs in development for VWD at the same time. “It’s nice to see multiple therapeutics coming through the pipeline, so that we’re not pinning all our hopes on just one drug.”
Using AI to Personalize Prophylaxis Dosing
Sidonio says that he and Ron Mathot (Amsterdam UMC) are currently working on a study using artificial intelligence (AI) and computer modeling to personalize prophylaxis for people with VWD and recurrent bleeding.
By feeding in clinical information and a few blood samples, the pop pK (pharmacokinetic) model aims to predict “what dose amount and how frequently you need it to get the VWF concentrate to achieve the optimal outcome,” Sidonio says. For example, some patients are willing to accept a few extra bleeds with less frequent treatment, while others prefer no bleeds with more intensive prophylaxis.
Instead of the current trial-and-error approach of “let’s start VWF concentrate prophy twice a week and see what happens,” this tool will hopefully lay out data-driven options up front and then be refined as patients are followed over time, he says.
According to Sidonio, this kind of modeling is especially important because VWD is so heterogeneous — meaning the disease and treatment needs are different for each person — and contributors such as weight, factor levels, type of VWD, bleed history, and age all likely influence how much prophylaxis a person really needs.
“We’re trying to figure out what troughs, what peaks, what areas under the curve are needed to stop certain types of bleeds,” he explains, noting that some VWD patients mostly have nosebleeds while others have musculoskeletal bleeds, so “they probably have different factor targets.”
Improved Testing and Identification Initiatives for VWD
Sidonio points out that while there have been improvements in VWD diagnosis, there is still work to be done to find everyone who has it.
To that end, several initiatives are underway to identify people who might be at risk for bleeding and get them tested. For example, vwdtest.com is a global initiative to improve access to testing, especially in areas where lab access is limited. In Canada, the Let’s Talk Period initiative aims to increase awareness of the signs and symptoms of VWD and other bleeding disorders.
“At our hospital, we have an algorithm in the emergency room so that when girls get seen for acute, heavy menstrual bleeding, they get connected to us, and we test them for VWD,” Sidonio says.
“Dr. Megan Brown and I started this initiative years ago and published the data, which showed that about 10% of the girls who come to the emergency room with really heavy periods end up having von Willebrand disease or other mild bleeding disorders.”