VONVENDI FOR SURGICAL USE
Indications1
VONVENDI is indicated in adult and pediatric patients with von Willebrand disease (VWD) for on-demand treatment and control of bleeding episodes, perioperative management of bleeding, and for adult patients only, routine prophylaxis to reduce the frequency of bleeding episodes.
100% of pediatric and adult patients experienced perioperative treatment success1*
of pediatric (4/4) and adult (15/15) VWD patients had a hemostatic efficacy rating of “Excellent” (100% pediatric, 60% adult) or “Good” (0% pediatric, 40% adult) using VONVENDI for perioperative use in clinical trials.1
*Treatment success was defined as achieving a hemostatic efficacy rating of “Excellent” or “Good.“1
Adult study description
Hemostatic efficacy of VONVENDI was evaluated in a prospective, open-label, multicenter trial in adults with severe VWD undergoing elective surgery. All 15 subjects who completed the study received a preoperative dose of 40–60 IU/kg VONVENDI 12–24 hours before surgery to raise FVIII to target levels. Within 3 hours prior to surgery, FVlll:C was assessed to confirm ≥30 IU/dL for minor and ≥60 IU/dL for major surgeries. Within 1 hour prior, VONVENDI was administered, with rFVIII added as needed. Overall hemostatic efficacy (the primary endpoint) was assessed 24 hours after last perioperative VONVENDI infusion or at completion of study, whichever occurred earlier, using a 4-point scale (Excellent=l, Good=2, Moderate=3, None=4).1
Primary endpoint
- Overall hemostatic efficacy assessed by the investigator 24 hours after last perioperative VONVENDI infusion or at completion of day 14 visit, whichever occurred earlier1
Secondary endpoints included1,2:
- Intraoperative hemostatic efficacy as assessed by the operating surgeon
- Intraoperative actual blood loss relative to predicted blood loss
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
Excellent: 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
Good: 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
Adult study safety
TEAEs were reported in 6 patients. 11 of 12 adverse events were considered unrelated to treatment: acne, anemia, deep vein thrombosis (DVT), diverticulitis, dizziness, dry skin, headache, joint swelling, nasopharyngitis, pelvic pain, and peripheral swelling. One DVT event, considered possibly related to VONVENDI, was managed throughout the postoperative period; it subsequently resolved.2
Pediatric study description
The multicenter, open-label trial evaluated the efficacy of VONVENDI with or without rFVIII in managing surgical bleeding in pediatric patients with severe VWD. Four patients completed the study and underwent 4 minor surgeries, including stage 2 buccal mucosa hypospadias reconstruction, tunneled central venous catheter with subcutaneous port removal (emergency), and circumcision. The mean dose of VONVENDI administered during the 4 surgeries was 94 IU/kg (mean 1.8 preoperative infusions) and 117 IU/kg (mean 2.3 postoperative infusions). One patient received 5 infusions of rFVIII (1 preoperative and 4 postoperative infusions) during 1 surgery.1
Pediatric study safety
In the 4 patients who underwent surgery, 2 patients reported 3 TEAEs. One TEAE of presyncope of mild severity was considered related to the study procedure of venipuncture.1,3
TEAE=treatment-emergent adverse event.
VONVENDI: an established safety profile
VONVENDI first received FDA approval for on-demand treatment and control of bleeding episodes in adults in 2015 and has 10 years of real-world use.1
VONVENDI is the first and only recombinant VWF treatment option for VWD. 1,4-6
- Recombinant products are manufactured without blood or human plasma, so there is virtually no risk of blood-borne pathogen transmission.7,8
VONVENDI's safety profile was established in 6 clinical trials1
- Of the 132 total study participants across 6 clinical studies, the following adverse reactions were observed: headache (n=18), vomiting (n=9), nausea (n=7), dizziness (n=4), generalized pruritus (n=3), hypertension (n=2), vertigo (n=2), tachycardia (n=1), infusion site paresthesia (n=1), chest discomfort and increased heart rate (n=1), hot flush (n=1), deep vein thrombosis (n=1), dysgeusia (n=1), tremor (n=1), electrocardiogram T wave inversions (n=1)1
- Across all studies and age groups, no study participants developed anaphylaxis or neutralizing antibodies.3
Although no study participants developed anaphylaxis or neutralizing antibodies across all studies, HCPs should continue to monitor for anaphylaxis and inhibitor development.3
Review Safety Data
See the overall safety profile and adverse events for VONVENDI
Read Dosing by Indication
Prophylaxis, on-demand, and perioperative dosing for VONVENDI1
Contact a Takeda Rep
Get in touch with a Takeda representative in your area
References
- VONVENDI [von Willebrand factor (Recombinant)] Prescribing Information.
- 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.
- Data on file, Takeda, Inc.
- ALPHANATE [antihemophilic factor/von Willebrand factor complex (human)] Prescribing Information.
- HUMATE-P [Antihemophilic Factor/von Willebrand Factor Complex (Human)] Prescribing Information.
- WILATE [von Willebrand Factor/Coagulation Factor VIII Complex (Human)] Prescribing Information.
- Franchini M, Mannucci PM. Von Willebrand factor (Vonvendi®): the first recombinant product licensed for the treatment of von Willebrand disease. Expert Rev Hematol. 2016;9(9):825-830.
- Turecek PL, Mitterer A, Matthiessen HP, et al. Development of a plasma- and albumin-free recombinant von Willebrand factor. Hamostaseologie. 2009;29 Suppl 1:S32-S38