Dosing of VONVENDI® [von Willebrand factor (Recombinant)], with or without recombinant factor VIII (rFVIII), should be based on patient need as determined by monitoring levels and clinical judgment.

On-demand clinical trial design and results1,2

A phase 3 prospective, multicenter, open-label study assessed the efficacy and safety of on-demand use of VONVENDI [von Willebrand factor (Recombinant)], with and without rFVIII, in adult patients with severe von Willebrand disease (VWD) over a period of 12 months.

The first dose of VONVENDI was administered together with rFVIII. Bleeding episodes were to be treated with an initial infusion of 40 to 60 IU/kg VWF:RCo rVWF for minor to moderate bleeds and up to 80 IU/kg VWF:RCo for major bleeds.

A total of 193 bleeding episodes were reported in 22 subjects exposed to VONVENDI. Treatment success (primary efficacy endpoint) was defined as a mean efficacy rating score of less than 2.5 for all bleeding episodes in a subject treated with VONVENDI (with or without rFVIII) using a pre-specified, 4-point rating (Excellent=1, Good=2, Moderate=3, None=4). 100% of patients experienced treatment success (18/18; 95% CI, 81.5-100).

Please see Safety profile for study-specific safety information

100% bleed control with an "Excellent" or "Good" rating1

During the pivotal trial, all bleeding episodes (N=192) were controlled with an efficacy rating of excellent (96.9%) or good (3.1%).

Efficacy Rating Scale

The efficacy rating was assessed on a 4-point scale (Excellent=1, Good=2, Moderate=3, None=4), with the investigation comparing the prospectively estimated number of infusions to treat the bleeding episode to the actual number of infusions administered. The efficacy outcome included the number of treated bleeding episodes with a hemostatic efficacy rating of excellent or good.

Bleeds stopped with the estimated number of infusions or fewer.

Minor bleeds stopped with only 1-2 more infusions than estimated. Major bleeds stopped with less than 1.5 times the estimated number of infusions.

Learn more about the Study Results

Bleeding episodes were treated with an initial infusion of 40 to 60 IU/kg of VONVENDI for minor to moderate bleeds and up to 80 IU/kg of VONVENDI for major bleeds. 2

The study protocol stipulated that the first dose of VONVENDI be administered together with rFVIII. However, according to dosing guidelines in the USPI, VONVENDI may be administered alone if an immediate rise in FVIII:C is not necessary, or if the baseline FVIII:C level is >40%.1,2

  • All 192 bleed treatments in the study (95% CI:98.1%-100.0%) were rated as either “Excellent” (96.9%, 186/192) or “Good” (3.1%, 6/192)1
  • Bleed control was defined as having an “Excellent” or “Good” rating
  • Bleeding episodes were treated with an initial infusion of 40-60 IU/kg of VONVENDI for minor to moderate bleeds and up to 80 IU/kg of VONVENDI for major bleeds2
  • A total of 8/125 (6.4%) of the adverse events (AEs) observed during the study were considered to have a causal relationship to VONVENDI and were subsequently resolved2

Ratings of “Excellent” or “Good” required that no additional von Willebrand factor (VWF) coagulation factor-containing product was needed. Sensitivity analysis of treatment success for bleeding episodes confirmed the primary analysis with 100% treatment success for each scenario.

1

infusion resolved the majority of bleeds, regardless of bleed location or severity1

The study protocol stipulated that the first dose of VONVENDI be administered together with rFVIII. However, according to dosing guidelines, VONVENDI may be administered alone if an immediate rise in FVIII:C is not necessary, or if the baseline FVIII:C level is ≥40%.1,2

  • 81.8% (157/192) of bleeds treated were resolved with 1 infusion (median 1, range 1-4)1
  • Major/Severe bleeds were resolved with a median of 2 infusions (range 1-3)1
Review the data
Number of infusions by severity of bleeding episode1
Number of infusions Minor n (%) (n=122) Moderate n (%) (n=61) Major/Severe n (%) (n=7) Unknown n (%) (n=2) All n (%) (n=192)
1 113 (92.6%) 41 (67.2%) 1 (14.3%) 2 (100%) 157 (81.8%)
2 8 (6.6%) 13 (21.3%) 4 (57.1%) 0 (0.0) 25 (13.0%)
3 1 (0.8%) 6 (9.8%) 2 (28.6%) 0 (0.0) 9 (4.7%)
4 0 (0.0) 1 (1.6%) 0 (0.0) 0 (0.0) 1 (0.5%)
Median 1 1 2 1 1
Range 1-3 1-4 1-3 1-1 1-4

1

infusion treated and controlled mucosal, gastrointestinal, and joint bleeds in the pivotal study1

The study protocol stipulated that the first dose of VONVENDI be administered together with rFVIII. However, according to dosing guidelines, VONVENDI may be administered alone if an immediate rise in FVIII:C is not necessary, or if the baseline FVIII:C level is ≥40%.1,2

Review the data
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VONVENDI® safety data.

Safety Data

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Reference: 1. VONVENDI [von Willebrand factor (recombinant)] Prescribing Information. 2. Gill JC, Castaman G, Windyga J, et al. Hemostatic efficacy, safety, and pharmacokinetics of a recombinant von Willebrand factor in severe von Willebrand disease. Blood. 2015;126(17):2038-2046.

Indications

VONVENDI [von Willebrand factor (recombinant)] is a recombinant von Willebrand factor (rVWF) indicated for use in adults (age 18 and older) diagnosed with von Willebrand disease (VWD) for:

  • On-demand treatment and control of bleeding episodes
  • Perioperative management of bleeding

Detailed Important Risk Information
CONTRAINDICATIONS

Do not use in patients who have had life-threatening hypersensitivity reactions to VONVENDI or its components (tri-sodium citrate-dihydrate, glycine, mannitol, trehalose-dihydrate, polysorbate 80, and hamster or mouse proteins).

WARNINGS AND PRECAUTIONS

Embolism and Thrombosis

Thromboembolic reactions, including disseminated intravascular coagulation, venous thrombosis, pulmonary embolism, myocardial infarction, and stroke, can occur, particularly in patients with known risk factors for thrombosis, including low ADAMTS13 levels. Monitor for early signs and symptoms of thrombosis such as pain, swelling, discoloration, dyspnea, cough, hemoptysis, and syncope, and institute prophylaxis measures against thromboembolism based on current recommendations.

In patients requiring frequent doses of VONVENDI in combination with recombinant factor VIII, monitor plasma levels for FVIII:C activity because sustained excessive factor VIII plasma levels can increase the risk of thromboembolic events.

One out of 80 subjects treated with VONVENDI in clinical trials developed proximal deep vein thrombosis in perioperative period after total hip replacement surgery.

Hypersensitivity Reactions

Hypersensitivity reactions have occurred with VONVENDI. These reactions can include anaphylactic shock, generalized urticaria, angioedema, chest tightness, hypotension, shock, lethargy, nausea, vomiting, paresthesia, pruritus, restlessness, blurred vision, wheezing and/or acute respiratory distress. Discontinue VONVENDI if hypersensitivity symptoms occur and administer appropriate emergency treatment.

Neutralizing Antibodies (Inhibitors)

Inhibitors to VWF and/or factor VIII can occur. If the expected plasma levels of VWF activity (VWF:RCo) are not attained, perform an appropriate assay to determine if anti-VWF or anti-factor VIII inhibitors are present. Consider other therapeutic options and direct the patient to a physician with experience in the care of either VWD or hemophilia A.

In patients with high levels of inhibitors to VWF or factor VIII, VONVENDI therapy may not be effective and infusion of this protein may lead to severe hypersensitivity reactions. Since inhibitor antibodies can occur concomitantly with anaphylactic reactions, evaluate patients experiencing an anaphylactic reaction for the presence of inhibitors.

ADVERSE REACTIONS

In clinical trials, the most common adverse reactions observed in ≥2% of subjects (n=80) were generalized pruritus, vomiting, nausea, dizziness, and vertigo.

One subject treated with VONVENDI in perioperative setting developed deep vein thrombosis after total hip replacement surgery.

Please see VONVENDI full Prescribing Information.