VONVENDI for Prophylaxis Treatment

Indications

VONVENDI [von Willebrand factor (recombinant)] is indicated in adult and pediatric patients with von Willebrand disease (VWD) for1:

For adult patients only:

VONVENDI prophylaxis reduced the number of bleeds in adults previously treating bleeds on-demand1

91.7% (11/12) of adults achieved treatment success reducing their ABR with VONVENDI prophylaxis, with treatment success defined as at least a 25% reduction in a patient’s historical ABR (12 months prior to study) for spontaneous bleeding episodes requiring factor treatment vs the on-study period of 12 months.1

Chart comparing pre-study and on-study annualized bleeding rates (ABR) in adults treated with VONVENDI prophylaxis that were previously treated on-demand. Pre-study ABR for spontaneous and traumatic bleeds was 4.0 (range: 3.0–156.0), reduced to 0.0 (range: 0.0–5.8) during the study. 91.7% of participants achieved at least a 25% reduction in ABR.

Pre-study and On-Study ABR was also assessed for All Spontaneous and Traumatic Bleeds and All Joint Bleeds. The median ABR for All Spontaneous and Traumatic Bleeds decreased from 4.5 to 0.5 and the ABR for All Joint Bleeds decreased from 1.5 to 0.1

*Based on descriptive statistics.1 †Based on bleeding and treatment history documented in medical records prior to the study.1
ABR=Annualized Bleed Rate; ALT=alanine aminotransferase; OD=on-demand; pdVWF=Plasma-derived Von Willebrand Factor; TEAE=treatment-emergent adverse event.

Study description

VONVENDI for routine prophylaxis was evaluated in a prospective, single-arm, open-label, international multicenter study enrolling 23 adults with VWD. Subjects were assigned by prior therapy to: a Prior on-demand group (n=12) or a Switch group previously on pdVWF prophylaxis (n=10), and received treatment for 12 months. The Prior on-demand group initiated VONVENDI at 50 ± 10 IU/kg twice weekly, while the Switch group received a starting VONVENDI dose matched (±10%) to their prior pdVWF regimen. Efficacy was measured by annualized bleeding rates for all bleeds, spontaneous bleeds, and joint bleeds.1

Study safety

Among patients who received prophylaxis with VONVENDI in the clinical trial, 17/23 (74%) experienced a total of 41 TEAEs. The following TEAEs were experienced by multiple subjects: headache (4 subjects), arthralgia (3 subjects), and ear infections, gastroenteritis, urinary tract infection (UTI), joint injury, and ALT increased (2 subjects each). Of these TEAEs, 1 report of headache (nonserious, moderate intensity) was considered related to VONVENDI and led to study discontinuation.2,3

Learn more about VONVENDI's established safety profile.

A majority of adult patients on pdVWF prophylaxis achieved treatment success after switching to VONVENDI prophylaxis1

For the Switch group in the VONVENDI prophylaxis study: 90% (9/10) of patients achieved treatment success, defined as achieving an on-study ABR (for 12 months) for spontaneous bleeding episodes requiring factor treatment that was no greater than their historical ABR (12 months prior to study) for treated episodes (preservation success).1,2

Chart showing median annualized bleeding rates (ABR) for treated spontaneous and traumatic bleeding events in patients who switched from pdVWF to VONVENDI prophylaxis. Pre-study ABR was 0.0 (range: 0.0–47.0), and on-study ABR remained at 0.0 (range: 0.0–12.1). 90% of patients (9/10) achieved treatment success by maintaining or reducing their ABR.

Pre-study and on-study ABR was also assessed for all spontaneous and traumatic bleeds and all joint bleeds. The median ABR for all spontaneous and traumatic bleeds increased from 1.0 to 3.6, and the ABR for all joint bleeds remained at 01

*Based on descriptive statistics.1
Based on bleeding and treatment history documented in medical records prior to the study.1

With VONVENDI prophylaxis, the majority of bleeds in adult Type 3 VWD patients were mild or moderate2

Chart showing the number and severity of all-cause bleeding events by anatomical location in adult Type 3 VWD patients on VONVENDI prophylaxis. Most bleeds were mild or moderate. Oral and mucosal bleeds were most common (27 events), followed by menorrhagia (4), multiple sites (3), muscle/soft tissue (1), and other (1). No CNS or hematuria bleeds occurred. Hemarthrosis decreased from 23 prior bleeds to 3 on-study; GI bleeds decreased from 2 to 0.

Limitations

This secondary outcomes analysis is based on descriptive statistics and is from a sample size of 10 patients; therefore, results should be interpreted with caution2

*Total treated/untreated (201) vs on study (38).2
Through Month 12.2
Other mucosa includes gum, mouth, and nose bleeds.2
§Patients with VWD Type 3 who were treated on-demand with any VWF during the 12-month period before entering this study.2
Historical.2

VONVENDI prophylaxis increased FVIII levels2

In adult patients with Type 3 VWD previously treated on-demand, VONVENDI prophylaxis increased trough FVIII levels 5-fold from baseline* and remained stable throughout 12 months of treatment with no additional prophylactic FVIII.2

Mean ± SD FVIII:C Trough Levels For Adult Patients With Type 3 VWD Treated With rVWF Prophylaxis and Available PK/PD Data: (A) Prior OD Group2

Line graph showing FVIII levels over time in adult Type 3 VWD patients treated with VONVENDI prophylaxis. FVIII:C levels increased fivefold from baseline (2.5 ± 0.9 IU/dL) at the prior on-demand stage to 24.2 ± 25.5 IU/dL at the initial PK visit, and remained stable through 12 months without additional prophylactic FVIII. Time points include baseline, initial PK visit, prophylaxis initiation, and months 1, 2, 3, 6, 9, and 12.

*Baseline visit, within 42 days of screening, after washout.2
rVWF=recombinant von Willebrand factor

VONVENDI prophylaxis led to a sustained FVIII rise in adult patients with severe Type 3 VWD1,2

Treatment of breakthrough bleeds should follow the on-demand dosing guidelines.1
Consider self-infusion with VONVENDI for your adult patients with VWD

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Prophylaxis, on-demand, and perioperative dosing for VONVENDI1

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References
  1. VONVENDI [von Willebrand factor (Recombinant)] Prescribing Information.
  2. Leebeek FWG, Peyvandi F, Tiede A, et al. Prophylaxis with recombinant von Willebrand factor in patients with type 3 von Willebrand disease: results of a post hoc analysis from a phase 3 trial. Eur J Haematol. 2023;111(1):29-40.
  3. Leebeek FWG, Peyvandi F, Escobar M, et al. Recombinant von Willebrand factor prophylaxis in patients with severe von Willebrand disease: phase 3 study results. Blood. 2022;140(2):89-98.