may be all you need to manage perioperative bleeding1

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.

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.

Phase 3 study in adult patients with severe VWD who were undergoing elective surgery1,2

A phase 3 prospective, multicenter, open-label study assessed the efficacy and safety of VONVENDI [von Willebrand factor (Recombinant)] with or without rFVIII in adults (age 18 years and older) diagnosed with severe von Willebrand disease (VWD) of all types undergoing surgery.

Fifteen subjects completed the trial. Ten subjects underwent major surgeries and 5 subjects underwent minor surgeries. All subjects were administered a 12 to 24 hour preoperative Fifteen subjects completed the trial. Ten subjects underwent major surgeries and 5 subjects underwent minor surgeries. All subjects were administered a 12 to 24 hour preoperative dose of 40 to 60 IU/kg of VONVENDI to increase the factor VIII levels to target levels. Within 3 hours prior to surgery, the subjects' FVlll:C levels were assessed to ensure that target of 30 IU/dL for minor surgeries and 60 IU/dL for major surgeries was achieved. Within 1 hour prior to surgery, subjects received a dose of VONVENDI. Recombinant Factor VIII was administered based on FVlll:C levels performed 3 hours prior to surgery. lntraoperative and postoperative dosing were individualized, with or without rFVIII, to maintain target trough levels according to the type of surgery for 14 days.

Primary endpoint was overall hemostatic efficacy

  • Assessed by the investigator 24 hours after last perioperative VONVENDI infusion or at completion of day 14 visit, whichever occurred earlier
  • Using a 4-point ordinal efficacy scale (“Excellent," “Good," “Moderate,” and “None") based on estimated expected versus actual blood loss, transfusion requirements and postoperative bleeding and oozing
  • A rating of Excellent or Good was required to declare the outcome a success

Secondary endpoints included

  • Intraoperative hemostatic efficacy as assessed by the operation surgeon
  • Intraoperative actual blood loss relative to predicted blood loss

100% (N=15) overall hemostatic efficacy across all types of VWD, for both major and minor surgeries.

Please see Safety profile for study-specific safety information Learn more about the Study Design

Range of surgical procedures1,2

Mucosal: Mouth and Oral Cavity

2 major

1 minor

Mucosal: Nasopharyngeal

2 minor

Mucosal: Genital Tract Female

1 major

Gastrointestinal

1 major

1 minor

Musculoskeletal: Joint

6 major

1 minor

In 15 adult patients with severe VWD, VONVENDI, with or without rFVIII, was used to manage perioperative bleeding in a range of major and minor surgical procedures.1,2

Timing of VONVENDI administration in elective surgeries1

12-24 hours before surgery

Patients received a preoperative VONVENDI dose of 40-60 IU/kg, administered to increase the factor VIII (FVIII) levels to target levels

Within 3 hours prior to surgeryMucosal: Nasopharyngeal

FVIII:C was assessed to ensure minimum target level was achieved

(30 IU/dL for minor, 60 IU/dL for major)

Based on these FVIII:C levels, VONVENDI was administered with or without rFVIII 1 hour prior to surgery

After surgery

Patients received postoperative infusions of VONVENDI, with or without rFVIII, to maintain hemostasis

In 15 adult patients with severe VWD, VONVENDI, with or without rFVIII, was used to manage perioperative bleeding in a range of major and minor surgical procedures.1,2

100% overall hemostatic efficacy for minor and major surgeries1

In the pivotal, phase 3 surgical study, all 15 participants treated with VONVENDI achieved an overall hemostatic efficacy of 100% (15/15) with a 90% confidence interval (CI) of 81.9% to 100% and intraoperative hemostatic efficacy of 100% with a 90% CI of 81.9% to 100.1

Learn more about the results
  • Overall and intraoperative results included a 90% CI of 81.9%-100%1
  • 9/15 patients achieved "Excellent" efficacy ratings and 6/15 patients achieved "Good" efficacy ratings1
  • The clinical trial included patients with all types of VWD, except Type 2N, who were undergoing either major or minor surgeries1,2

Efficacy was defined as a mean rating score of ≤2, assessed using a 4-point rating scale (Excellent=1, Good=2, Moderate=3, None=4).1

Hemostasis achieved with VONVENDI, with or without recombinant factor VIII (rFVIII), was as good or better than expected for a hemostatically normal patient undergoing the same type of surgery.1

Hemostasis achieved with VONVENDI, with or without rFVIII, was probably as good as expected for a hemostatically normal patient undergoing the same type of surgery.1

1

factor was all most patients needed2,a

1

dose per day was all most patients needed for postoperative bleeding management2,c

  • Postoperative bleeding in 12/15 patients was managed by VONVENDI alone2
  • 13/15 patients in the study received VONVENDI postoperatively2
  • Two patients undergoing minor surgery did not require any postoperative infusions2

aVONVENDI contains only trace amounts of rFVIII.
bOf the 5 patients who did receive concomitant rFVIII, 2 patients received a preoperative infusion (1 infusion each), 2 patients received a postoperative infusion (1 infusion each), and 1 patient received both one preoperative and 6 postoperative infusions.
cTwo patients undergoing major surgery required more frequent dosing of VONVENDI.

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Reference: 1. VONVENDI [von Willebrand factor (recombinant)] Prescribing Information. 2. Peyvandi F, Mamaev A, Wang JD, et al. Phase 3 study of recombinant von Willebrand factor in patients with severe von Willebrand disease who are undergoing elective surgery. J Thromb Haemost. 2019;17(1):52-62.

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.