VONVENDI FOR ON-DEMAND 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 on- demand treatment success1*
of bleeds in pediatric and adult VWD patients received an efficacy rating of “Excellent” (97% adults, 99% pediatric) or “Good” (3% adults, 1% pediatric) using VONVENDI for on-demand use in clinical trials.1
*Treatment success (the primary endpoint) was defined as a mean efficacy rating score of less than 2.5 for all bleeding episodes, assessed on a 4-point rating scale (Excellent=1, Good=2, Moderate=3, None=4) with the investigator comparing the prospectively estimated number of infusions needed to treat the bleeding episode to the actual number of infusions administered.1
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Adult study description
Hemostatic efficacy of VONVENDI was studied in a multicenter, open-label trial investigating various dosing strategies with or without rFVIII for on-demand treatment and control of bleeding in adults with von Willebrand disease. Initial bleeds were treated with VONVENDI plus rFVIII at a 1.3:1 ratio (30% more VONVENDI), followed by VONVENDI with or without rFVIII. rFVIII use was guided by FVlll:C levels to maintain plasma concentrations above 40 IU/dL (40%). A total of 192 bleeding episodes were treated with VONVENDI on-demand in 22/37 patients. Of the 22 patients, those with GI bleeds (n=2) and those in whom the number of infusions to control a BE was estimated retrospectively (n=2) were excluded from the primary analysis.1
Primary endpoint
- Number of study participants with treatment success for control of bleeding episodes1
- Treatment success was defined as a mean efficacy rating score of less than 2.5 for all bleeding episodes in a participant treated with VONVENDI1
Secondary endpoints included:
- The number of treated bleeding episodes with an efficacy rating of “Excellent” or “Good”1
- The number of infusions and number of units of VONVENDI administered with and without rFVIII per bleeding episode1
The efficacy rating was assessed on a 4-point scale (Excellent=1, Good=2, Moderate=3, None=4), with the investigator comparing the prospectively estimated number of infusions needed to treat the bleeding episode to the actual number of infusions administered.1
Excellent: Bleeds stopped with the estimated number of infusions or fewer.1
Good: 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.1
Adult study safety
8/125 (6.4%) of AEs observed during the trial were considered to have a causal relationship to VONVENDI; they subsequently resolved. 6/8 (75%) of AEs in 4 subjects were not serious (mild infusion site paresthesia, moderate dysgeusia, moderate tachycardia [n=1], mild electrocardiogram T wave inversion, mild generalized pruritus, mild hot flush [n=1 each]). One patient experienced 2 simultaneous serious AEs (chest discomfort and increased heart rate); symptoms improved after 10 minutes of oxygen therapy with a full recovery within 3 hours.2
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Pediatric study description
Hemostatic efficacy of VONVENDI with or without rFVIII for on-demand treatment of non-surgical bleeds was studied in a multicenter, open-label trial in 18 pediatric patients with severe VWD. Patients were followed for ≥12 months. Twenty-eight bleeds in 7 patients were treated with VONVENDI (40-60 IU/kg; median 48, range 18-63) plus rFVIII (30-45 IU/kg; median 33, range 9-45). Seventy-six bleeds in 15 patients were treated with VONVENDI alone (40-60 IU/kg; median 49, range 18-86) when baseline FVIII ≥30%. In 8 patients, 18 bleeds required at least 1 additional VONVENDI dose every 8-24 hours to maintain VWF:RCo and FVIII levels.1
Pediatric study safety
Of the 122 TEAEs observed in the trial, 1 TEAE of nausea (moderate in severity) was considered to have a causal relationship to VONVENDI.3
TEAE=treatment-emergent adverse event.
A single infusion of VONVENDI resolved the majority of bleeds in adults
(157/192) OF BLEEDS TREATED WERE RESOLVED WITH 1 INFUSION (MEDIAN 1, RANGE 1-4)2
- Major/severe bleeds were resolved with a median of 2 infusions (range 1-3)2
The study protocol stipulated that the first dose of VONVENDI be administered together with recombinant factor VIII (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
infusions per
bleed
n (%)
(n=122)
n (%)
(n=61)
n (%)
(n=7)
n (%)
(n=2)
n (%)
(n=192)
A single infusion of VONVENDI resolved the majority of on-demand bleeds in pediatric patients1
OF 104 BLEEDS WERE CLEARED UP AFTER JUST 1 INFUSION (MEDIAN 1, RANGE 1-9); 94% WITH 1-2 INFUSIONS3
infusions per
bleed
n (%)
(n=48)
n (%)
(n=31)
n (%)
(n=2)
n (%)
(n=23)
n (%)
(n=104)
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. 1,5-7
- Recombinant products are manufactured without blood or human plasma, so there is virtually no risk of blood-borne pathogen transmission.8-9
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
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References
- VONVENDI [von Willebrand factor (Recombinant)] Prescribing Information.
- 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.
- Data on file, Takeda, Inc.
- 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