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Beth benderfynodd Grŵp Asesu Meddyginiaethau Cymru’n Un?

Gellir rhoi vonicog alfa i drin cyfnodau o waedu mewn plant a phobl ifanc hyd at 17 oed sydd â chlefyd von Willebrand difrifol. Mae clefyd von Willebrand yn gyflwr etifeddol lle nad yw'r gwaed yn ceulo'n iawn, gan achosi i bobl waedu'n haws. Gellir rhoi vonicog alfa i drin cyfnodau o waedu mewn argyfyngau a hefyd ar ôl llawdriniaethau llawfeddygol wedi'u cynllunio. Dim ond pan nad yw triniaeth â desmopressin wedi gweithio neu pan nad yw'n addas y gellir rhoi vonicog alfa.   

Bydd vonicog alfa ar gael i gleifion cymwys sydd wedi cofrestru gyda phractis meddyg teulu yng Nghymru, hyd yn oed os oes angen iddynt dderbyn eu triniaeth y tu allan i Gymru. Bydd vonicog alfa yn cael ei roi gan feddygon sy'n arbenigo mewn trin anhwylderau gwaedu mewn plant yn unig.

Nid yw vonicog alfa wedi’i drwyddedu i drin gwaedu mewn plant neu bobl ifanc sydd â chlefyd von Willebrand, felly os caiff ei ddefnyddio yn y modd hwn fe’i gelwir yn ddefnydd “all-drwydded”. Pan gaiff meddyginiaeth ei defnyddio yn “all-drwydded”, rhaid i'ch meddyg, neu feddyg eich plentyn, esbonio'n glir i chi y risgiau a'r manteision o gymryd y feddyginiaeth. Dylai eich meddyg roi gwybodaeth glir i chi, siarad â chi am eich opsiynau a gwrando'n ofalus ar eich barn a'ch pryderon. Darllenwch ein taflen wybodaeth i gleifion am ddefnydd di-drwydded ac all-drwydded o feddyginiaethau.

Mae Grŵp Asesu Meddyginiaethau Cymru'n Un ac AWTTC yn adolygu'r penderfyniad hwn yn rheolaidd i weld a oes unrhyw dystiolaeth newydd a allai effeithio ar y penderfyniad hwn.

I gael rhagor o wybodaeth am glefyd von Willebrand ewch i: The Haemophilia Society (Saesneg yn unig)

What did the One Wales Medicines Assessment Group decide?

Vonicog alfa can be given to treat episodes of bleeding in children and young people aged up to 17 years with severe von Willebrand disease. Von Willebrand disease is an inherited condition where the blood does not clot properly, causing people to bleed more easily. Vonicog alfa can be given to treat episodes of bleeding in emergencies and also after planned surgical operations. Vonicog alfa can only be given when treatment with desmopressin has not worked or is not suitable.   

Vonicog alfa will be available to eligible patients who are registered with a GP practice in Wales, even if they need to receive their treatment outside Wales. Vonicog alfa will be given only by doctors who are specialists in the treatment of bleeding disorders in children.

Vonicog alfa is not licensed to treat bleeding in children or young people with von Willebrand disease, so using it in this way is called “off-label” use. When a medicine is used “off-label” your doctor, or your child’s doctor, must clearly explain to you the risks and benefits of taking the medicine. The doctor should give you clear information, talk with you about the options available and listen carefully to your views and concerns. Read our patient information leaflet about unlicensed and off-label use of medicines

The One Wales Medicines Assessment Group and AWTTC review this decision regularly to see if there is any new evidence that may affect this decision.

For more information about Von Willebrand disease visit: The Haemophilia Society

These criteria are in accordance with the Welsh Health Specialised Services Committee Policy Position PP215: Vonicog alfa for the treatment and prevention of bleeding in people of all ages with von Willebrand disease (October 2023)¹.

Starting criteria: Vonicog alfa will be routinely commissioned for treatment of haemorrhage and surgical bleeding, and prevention of surgical bleeding, in children aged up to 17 years with a confirmed diagnosis of von Willebrand disease (VWD), in the following circumstances:

• when desmopressin with or without tranexamic acid treatment is ineffective or not indicated (based on UK clinical practice), and
• when von Willebrand Factor (VWF) activity levels are <50 IU/dl OR diagnosis is type 2N VWD, and
• there is no evidence of inhibitors to VWF.

Retreatment for the same bleeding episode or surgery should be guided by clinical presentation, considering the half-life of vonicog alfa, with careful monitoring of the necessary laboratory parameters and the patient. Patients, or their carers, should be encouraged to provide their clinical team with information on treatments received for the previous bleeding episode or surgery and related clinical sequelae.

Vonicog alfa should not be prescribed for routine prophylaxis.

Dosage and frequency of administration must be individualised according to clinical judgement and based on the patient´s weight, type and severity of the bleeding episodes/surgical intervention and based on monitoring of appropriate clinical and laboratory measures. Dosing may require adjustment in underweight or overweight patients. Further information about dose calculations can be found in the Summary of Product Characteristics (SmPC)².

Stopping criteria: Treatment with vonicog alfa should be monitored and compared to the effectiveness with previous treatment episodes. Treatment should be discontinued if the following occur:

• reduced or poor control of bleeding with vonicog alfa compared with previous treatment episodes
• unexpected bleeding despite maintenance of therapeutic levels of VWF activity (50 IU/dl or more)
• emergence of adverse effects considered linked to vonicog alfa, such as DVT, hypersensitivity, and infusion-related reactions
• development of anti-VWF neutralising or binding antibodies.

Continuation of treatment: Healthcare professionals are expected to review a patient’s health at regular intervals to ensure they are demonstrating an improvement to their health due to the treatment being given. If no improvement to a patient’s health has been recorded then clinical judgement on the continuation of treatment must be made by the treating healthcare professional.

References:

1. The Welsh Health Specialised Services Committee (WHSSC). PP125 Vonicog alfa for the treatment and prevention of bleeding in people of all ages with von Willebrand disease. October 2023. Available at: https://whssc.nhs.wales/commissioning/whssc-policies/all-policy-documents/vonicog-alfa-for-the-treatment-and-prevention-of-bleeding-in-people-of-all-ages-with-von-willebrand-disease-policy-position-statement-pp2151/. Accessed December 2024.
2. Takeda UK Ltd. VEYVONDI^®. Summary of Product Characteristics. Sep 2024. Available at: https://www.medicines.org.uk/emc/product/11233/smpc#gref. Accessed December 2024.

Health boards will take responsibility for implementing One Wales Medicines Assessment Group decisions and ensuring that a process is in place for monitoring clinical outcomes. 

This is a summary of new evidence available and patient outcome data collected to inform the last review in December 2024.  

Background: Von Willebrand disease (VWD) is an inherited genetic disorder caused by a missing or defective clotting glycoprotein called von Willebrand factor (VWF), which is essential for normal haemostasis. VWF binds factor VIII (a key clotting protein) and platelets in blood vessel walls, which help form a platelet plug during the clotting process. People with VWD are not able to form this platelet plug, or it takes longer to form.

There is currently no cure for VWD. Clinical practice recommendations for diagnosis, treatment and follow-up were published in 2014 by the United Kingdom Haemophilia Centre Doctors Organisation (UKHCDO). International guidelines produced by the American Society of Haematology (ASH), the International Society on Thrombosis and Haemostasis (ISTH), the National Haemophilia Foundation (NHF), and the World Federation of Haemophilia (WFH) were also published in 2021 to support patients, clinicians, and health care professionals in their decisions about management of VWD. The aim of treatment is to correct the clotting process and reduce the extended bleeding time in people with VWD.

Vonicog alfa is the only recombinant VWF developed for substitution therapy in VWD. It is licensed for use in adults and is commissioned by the NHS Wales Joint Commissioning Committee (JCC). Welsh clinical experts indicated there was an unmet medical need for alternative therapies to the current plasma-derived blood products used in children which have a theoretical risk of transmission of plasma‑borne pathogens. This treatment is currently commissioned by JCC for use in children on the basis of the One Wales decision.

The Infected Blood Inquiry report published in May 2024 stated that some people with severe von Willebrand disorder are still being treated with plasma-based factor products; one of the recommendations from the Inquiry is that recombinant coagulation factor products should be offered in place of plasma-derived ones where clinically appropriate and that such treatment decisions should be funded accordingly. This recommendation is particularly pertinent to paediatric patients who are likely to be plasma product naïve.

Current One Wales decision: Supported for on demand treatment.

Licence status: Off-label use for this licensed medicine.

Vonicog alfa (Veyvondi^®) is licenced for the prevention and treatment of haemorrhage or surgical bleeding in adults (age 18 years and older) with von Willebrand disease (VWD), when desmopressin (DDAVP) treatment alone is ineffective or contraindicated. In January 2024, the license was extended to include long-term prophylaxis in adults. [commercial in confidence information removed].

Guidelines: There have been no relevant updates to existing guidelines identified.

Licensed alternative medicines or Health Technology Assessment advice for alternative medicines: No new medicines or Health Technology Assessment advice reported.

Effectiveness: The repeat literature search found one case study of interest. Tran et al (2023) reported an 8-year-old, Caucasian male diagnosed with mild VWD type 1 with a history of anaphylaxis to Humate-P (plasma-derived VWF blood product) who received vonicog alfa prior to elective orthopaedic surgery. The patient tolerated the recombinant VWF with no notable post infusion-related adverse effects or procedure complications. The patient did require oral aminocaproic acid (an antifibrinolytic) three days post operation due to mild skin bleeding, but he did not require any additional recombinant VWF post operation.

There are currently two active clinical trials:

• A phase 3, prospective, multicentre, uncontrolled, open-label clinical study to determine the efficacy, safety, and tolerability of rVWF with or without rFVIII (Advate^®) in the treatment and control of bleeding episodes, the efficacy and safety of rVWF in elective and emergency surgeries, and the pharmacokinetics of rVWF in children diagnosed with severe von Willebrand disease (NCT02932618). This study is still recruiting but has a primary completion date January 2025.
• A phase 3b, prospective, open-label, uncontrolled, multicentre study on long‑term safety and efficacy of rVWF in paediatric and adult subjects with severe von Willebrand disease (NCT03879135). This study is due to complete in March 2025.

There is a pending clinical trial which will evaluate the effectiveness of prophylaxis with rVWF in children which is due to complete in February 2027 (NCT05582993). Although not pertinent to the indication in this report, this trial may provide some useful safety data for the use of rWF in paediatric patients.

Safety: Outcome data provided by the Cardiff Haemophilia Centre report no adverse events, either at the time of infusion or in the recovery period. No other relevant safety analyses were identified in the repeat literature search.

Cost-effectiveness: No relevant cost-effectiveness analyses were identified in the repeat literature search.

Budget impact: There have been six paediatric patients in Wales treated with vonicog alfa, each for a single bleeding event, between August 2023 and October 2024. The dose given ranged from 650 IU to 2600 IU with the number of doses per patient ranging from 1 to 13. [Confidential information removed]. The total cost associated with the use of vonicog alfa over the 17-month period reported is [confidential data removed]. This compares favourably with that estimated for the time period covered by the previous review which was [confidential data removed] over 18 months and with the original yearly estimate of [confidential data removed]. None of these estimates include VAT. 

In the original budget impact, it was assumed that one dose of vonicog alfa would be used in a population of twenty children (20 doses), assuming some vial wastage. To take account of the varying ages of the population a mid-point age was used. Calculations were based on the average weight of a 9-year old child receiving a vonicog alfa dose of 46.5 IU/kg and a rFVIII dose of 33.6 IU/kg. As was noted in the previous review, actual usage data shows that fewer children than predicted receive treatment with vonicog alfa per year but in general, more than one dose is required per bleeding episode (mean number of doses 4.5, range 1-13). Additionally, concomitant rVIII is not required in many patients. Despite quite differing results in terms of doses used and patient uptake, the budget impact was lower in Year 2 when compared to the original estimates. AWTTC will continue to monitor patient uptake as part of ongoing reviews.

Impact on health and social care services: Minimal. 

Patient outcome data: Data have been received for six patients (age range 3 -17 years) in Wales each treated with vonicog alfa for a single bleeding event. All patients were treated at the Cardiff Haemophilia Centre which treats paediatric patients from all health board areas apart from Betsi Cadwaladr UHB in North Wales. No patient outcome data has been received for patient’s resident in North Wales and who would generally receive this specialist treatment at Alder Hey Children’s Hospital in Liverpool.

[Confidential information removed]. Resolution of bleeding was reported for all patients treated with vonicog alfa with no requirement to escalate to third-line treatments. No post-surgical complications were reported.

Evaluation of evidence: No significant new evidence has been published which challenges the original recommendation. Outcome data provided suggest that this treatment has been well tolerated and associated with resolution of symptoms. The number of doses used is higher than originally predicted. However, the overall budget impact is lower than the original estimate due to the number of patients treated. AWTTC will continue to monitor this as part of the review process and report back to OWMAG. AWTTC recommends continuing access in Wales to vonicog alfa for the on-demand treatment of non-surgical and surgical (elective and emergency) bleeding episodes in children aged up to 17 years with von Willebrand disease.

Next review date: December 2026

References: a full reference list is available on request.

Disclaimer: This document includes evidence published since the last review or full assessment of this medicine for the indication under consideration. It does not replace the original full evidence status report. Any previous reviews and the original full evidence status report are available from this webpage in the document history section.

Care has been taken to ensure the information is accurate and complete at the time of publication. However, the All Wales Therapeutics and Toxicology Centre (AWTTC) do not make any guarantees to that effect. The information in this document is subject to review and may be updated or withdrawn at any time. AWTTC accept no liability in association with the use of its content. An Equality and Health Impact Assessment (EHIA) has been completed in relation to the One Wales policy and this found there to be a positive impact. Key actions have been identified and these can be found in the One Wales Policy EHIA document.

Information presented in this document can be reproduced using the following citation: All Wales Therapeutics & Toxicology Centre.  One Wales Interim Decision. Vonicog alfa (Veyvondi^®▼) for on-demand treatment of non-surgical and surgical (elective and emergency) bleeding episodes in children aged up to 17 years with von Willebrand disease (OW19). 2025

Copyright AWTTC 2025. All rights reserved. 

• Second review: One Wales Interim Decision and review report December 2024 PDF 149KB
• First review: One Wales Interim Decision and review report November 2023 PDF 149KB
• Original assessment: One Wales Interim Decision with rationale November 2022 PDF 117KB
• Original assessment: Evidence Status Report November 2022 PDF 286KB