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ASH 2025 Nonmalignant Hematologic Disorders

CE / CME

Emerging Data and Clinical Implications in Nonmalignant Hematologic Disorders: ASH 2025 Highlights

Physician Assistants/Physician Associates: 1.00 AAPA Category 1 CME credit

Pharmacists: 1.00 contact hour (0.1 CEUs)

Physicians: maximum of 1.00 AMA PRA Category 1 Credit™

Nurse Practitioners/Nurses: 1.00 Nursing contact hour

Released: February 20, 2026

Expiration: August 19, 2026

Hanny Al-Samkari
Hanny Al-Samkari, MD
Joseph J. Shatzel
Joseph J. Shatzel, MD, MCR
CME/CE Information

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VIVID 3: Study Design

Joseph J. Shatzel, MD, MCR:
VIVID 3 is a very interesting phase Ib study in patients with symptomatic VWD, a highly heterogeneous bleeding disorder. The von Willebrand protein is involved in primary hemostasis and can become dysfunctional in a variety of ways. Some patients have a rather severe bleeding disorder, and others can have mild bleeding diathesis. Unlike other bleeding disorders like hemophilia, where there is a variety of long-acting prophylactic medicines, there is not yet such treatment for VWD. Patients can be given von Willebrand factor, but its half-life is not very long and requires frequent infusions. 

Investigators aimed to develop an effective, longer-acting prophylactic medicine for these patients. They developed a monoclonal antibody to protein S (VGA039) and hypothesized that it would alter the hemostatic milieu in such a way that patients with VWD would have less bleeding but not develop thrombosis. This study included patients 12-60 years of age with symptomatic VWD of any type. Patients could not have factor VIII activity that was above the lower limit of normal and no history of blood clots or prothrombotic disorders. They also excluded patients who received estrogen-containing hormonal therapy within 56 days of study drug, an important point because many premenopausal women with VWD take these drugs.  

Participants were divided into 2 cohorts. One arm received a flat dose of VGA039 subcutaneously every 4 weeks for 16 weeks. The other cohort received a weight-banded flat dose, and participants were allowed to transition to the open-label extension phase. This study's endpoints were safety, pharmacokinetics/pharmacodynamics, and annualized bleeding rate (ABR) reductions.6

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VIVID 3: Baseline Characteristics

Joseph J. Shatzel, MD, MCR:
These were younger patients, on average in their 20s to 30s, although some patients were older than 50 years of age. These cohorts were small (6 and 10 patients per cohort), but the variety of VWD types was broad and tended to reflect what is observed in the clinic. Some patients had reasonable bleeding rates, and the ABR at enrollment covered a broad range.6

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VIVID 3: Safety

Joseph J. Shatzel, MD, MCR:
In total, 16 patients received at least 4 doses of VGA039. None withdrew. There were no thrombotic events. There were no injection-site reactions. The only AEs were low-grade headache in 1 patient. There was 1 serious AE of unrelated severe GI bleeding in a patient with a history of GI bleeds. D-dimer, which was used as a prothrombotic measurement, was not elevated significantly.6

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VIVID 3: Reductions in Bleeding Rates Among Patients Completing Treatment Period

Joseph J. Shatzel, MD, MCR:
Although not the primary endpoint, efficacy is worth noting. Here, investigators present 8 patients, with a median bleed reduction, in terms of ABR, of 81%, which is striking for a disease without long-acting subcutaneous therapies available. When looking at ABR reductions by subgroup, patients who switched from prior prophylaxis had a pretty high ABR reduction, 75% to 100%. Patients with no prior prophylaxis had ABR reductions of 41% to 100%.6

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VIVID 3: Summary

Joseph J. Shatzel, MD, MCR:
The concept of this study is quite compelling, mostly because there is not a biologic therapy that fits in the VWD space. Although this study was small and results are preliminary, if the data are durable, the safety signal is maintained, and the efficacy signal remains high, this agent could easily advance to become a treatment option. I think the biggest concern is the thrombotic risk. In a larger study, we may see deep vein thrombosis or pulmonary embolism, which is challenging to treat in some bleeding disorders.

Hanny Al-Samkari, MD:
These data are really interesting. I agree that we need a treatment for patients with severe VWD. Most patients with VWD have relatively mild type 1 disease and do not necessarily need a prophylactic emicizumab-like therapy, but for patients with more significant bleeding, this could be life-changing. The risk for thrombosis is a potential concern. It is reassuring that certain markers, like D-dimer, were not elevated, but I agree that a larger study is warranted. One question that remains to be addressed is whether an anticoagulant could be safely given to patients who develop thrombosis while on this treatment.

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