Last Review Date: 06/04/2024

Date of Origin: 12/16/2014

Dates Reviewed: 12/2014, 04/2015, 05/2015, 09/2015, 12/2015, 03/2016, 06/2016, 12/2016, 06/2017, 09/2017, 11/2017, 11/2018, 03/2019, 10/2019, 02/2020, 06/2021, 03/2022, 06/2022, 06/2023, 06/2024

1. Length of Authorization

Coverage is provided for 3 months and may be renewed thereafter, unless otherwise specified*.

Note: The cumulative amount of medication the patient has on-hand will be taken into account for authorizations. Up to 5 ‘on-hand’ doses for the treatment of acute bleeding episodes will be permitted at the time of the authorization request.

* Initial and renewal authorization periods may vary by specific covered indication

2. Dosing Limits

1. Quantity Limit (max daily dose) [NDC Unit]:

• Vonvendi 450-850 units: 82 vials per 90-day supply
• Vonvendi 900-1700 units: 41 vials per 90-day supply

2. Max Units (per dose and over time) [HCPCS Unit]:

• 36,800 billable units per 90 day supply

3. Initial Approval Criteria ^1,2,8,10-12

Coverage is provided in the following conditions:

• Patient is at least 18 years of age; AND

Von Willebrand Disease (vWD) † Ф

• Diagnosis of von Willebrand disease has been confirmed by blood coagulation and von Willebrand factor testing; AND

• Used as treatment in at least one of the following:
  • • • • • On-demand treatment and control of bleeding episodes; AND

• Patient has severe vWD; OR
• Patient has mild or moderate vWD and the use of desmopressin is known or suspected to be ineffective or contraindicated; OR
  • • Perioperative management of bleeding (Note: Authorizations valid for 1 month); OR

• Routine prophylaxis to reduce the frequency of bleeding episodes; AND

• Patient has severe Type 3 vWD and is receiving on-demand therapy

† FDA Approved Indication(s); ‡ Compendia Recommended Indication(s); Ф Orphan Drug

4. Dispensing Requirements for Rendering Providers (Hemophilia Management Program)

• Prescriptions cannot be filled without an expressed need from the patient, caregiver or prescribing practitioner. Auto-filling is not allowed.
• Monthly, rendering provider must submit for authorization of dispensing quantity before delivering factor product. Information submitted must include:
  • • Original prescription information, requested amount to be dispensed, vial sizes available to be ordered from the manufacturer, and patient clinical history (including patient product inventory and bleed history)
    • Factor dose should not exceed +1% of the prescribed dose and a maximum of three vials may be dispensed per dose. If unable to provide factor dosing within the required threshold, below the required threshold, the lowest possible dose able to be achieved above +1% should be dispensed. Prescribed dose should not be increased to meet assay management requirements.
• The cumulative amount of medication(s) the patient has on-hand should be taken into account when dispensing factor product. Patients should not have more than 5 extra doses on-hand for the treatment of acute bleeding episodes.
• Dispensing requirements for renderings providers are a part of the hemophilia management program. This information is not meant to replace clinical decision making when initiating or modifying medication therapy and should only be used as a guide.

5. Renewal Criteria ^1,2,8,10

      Coverage may be renewed based upon the following criteria:

• Patient continues to meet the indication-specific relevant criteria identified in section III; AND
• Absence of unacceptable toxicity from the drug. Examples of unacceptable toxicity include: hypersensitivity reactions (including anaphylactic shock, generalized urticaria, angioedema, chest tightness, hypotension, shock, lethargy, nausea, vomiting, paresthesia, pruritus, restlessness, blurred vision, wheezing and/or acute respiratory distress), thromboembolic reactions (including disseminated intravascular coagulation [DIC], thromboembolism, venous thrombosis, pulmonary embolism, myocardial infarction, and stroke), development of neutralizing antibodies (inhibitors), etc.; AND
• Any increases in dose must be supported by an acceptable clinical rationale (i.e., weight gain, half-life study results, increase in breakthrough bleeding when patient is fully adherent to therapy, etc.); AND
• The cumulative amount of medication(s) the patient has on-hand will be taken into account when authorizing. The authorization will allow up to 5 doses on-hand for the treatment of acute bleeding episodes as needed for the duration of the authorization; AND

     On-demand treatment and control of bleeding episodes

• Renewals will be approved for a 6 month authorization period

     Perioperative management of surgical bleeding

• Coverage may NOT be renewed

     Routine prophylaxis to reduce the frequency of bleeding episodes

• Renewals will be approved for a 12 month authorization period; AND
• Patient has demonstrated a beneficial response to therapy (i.e., the frequency of bleeding episodes has decreased from pre-treatment baseline)

6. Dosage/Administration ¹

7. Billing Code/Availability Information

HCPCS Code & NDC(s):

8. References

1. Vonvendi [package insert]. Lexington, MA; Takeda Pharmaceuticals USA, Inc.; March 2023. Accessed May 2024.
2. Guidelines for the Management of Hemophilia. 3rd Edition. World Federation of Hemophilia 2020. Available at: https://www1.wfh.org/publications/files/pdf-1863.pdf.   Accessed May 2024.
3. Graham A1, Jaworski K. Pharmacokinetic analysis of anti-hemophilic factor in the obese patient. Haemophilia. 2014 Mar;20(2):226-9.
4. Croteau SE1, Neufeld EJ. Transition considerations for extended half-life factor products. Haemophilia. 2015 May;21(3):285-8.
5. Mingot-Castellano, et al. Application of Pharmacokinetics Programs in Optimization of Haemostatic Treatment in Severe Hemophilia a Patients: Changes in Consumption, Clinical Outcomes and Quality of Life. Blood. 2014 December; 124 (21).
6. MASAC Recommendation Concerning Prophylaxis for Hemophilia A and B with and without Inhibitors. MASAC Document #267; April 2022. Available at: https://www.bleeding.org/healthcare-professionals/guidelines-on-care/masac-documents/masac-document-267-masac-recommendation-concerning-prophylaxis-for-hemophilia-a-and-b-with-and-without-inhibitors. Accessed May 2024.
7. MASAC Recommendations Regarding the Treatment of von Willebrand Disease. MASAC Document #266; March 2021. Available at: https://www.bleeding.org/healthcare-professionals/guidelines-on-care/masac-documents/masac-document-266-masac-recommendations-regarding-the-treatment-of-von-willebrand-disease. Accessed May 2024.
8. Connell NT, Flood VH, Brignardello-Petersen R, et al. ASH ISTH NHF WFH 2021 guidelines on the management of von Willebrand disease. Blood Advances, Volume 5, Issue 1, 2021, Pages 301-325,  https://doi.org/10.1182/bloodadvances.2020003264.
9. Franchini M, Seidizadeh, Mannucci P, et al. Prophylactic management of patients with von Willebrand disease. Ther Adv Hematol. 2021; 12: 20406207211064064. Published online 2021 Dec 22. doi: 10.1177/20406207211064064.
10. MASAC Recommendations Concerning Products Licensed For The Treatment Of Hemophilia And Selected Disorders of the Coagulation System. MASAC Document #284 (Replaces Document #280); April 2024. Available at https://www.bleeding.org/healthcare-professionals/guidelines-on-care/masac-documents/masac-document-284-masac-recommendations-concerning-products-licensed-for-the-treatment-of-hemophilia-and-selected-disorders-of-the-coagulation-system. Accessed May 2024.
11. James PD, Connell NT, Ameer B, et al. ASH ISTH NHF WFH 2021 guidelines on the diagnosis of von Willebrand disease. Blood Adv. 2021 Jan 12;5(1):280-300. doi: 10.1182/bloodadvances.2020003265. PMID: 33570651; PMCID: PMC7805340.
12. James P. (2023). von Willebrand disease (VWD): Treatment of minor bleeding, use of DDAVP, and routine preventive care. In Leung LLK, Tirnauer JS (Eds.), UptoDate. Last updated: Sept 11, 2023. Accessed on: May 8, 2024. Available from https://www.uptodate.com/contents/von-willebrand-disease-vwd-treatment-of-minor-bleeding-use-of-ddavp-and-routine-preventive-care?search=von%20willebrand%20disease&source=search_result&selectedTitle=4%7E150&usage_type=default&display_rank=4.
13. First Coast Service Options, Inc. Local Coverage Article: Billing and Coding: Hemophilia Factor Products (A56482). Centers for Medicare & Medicaid Services Inc. Updated on 09/29/2023 with effective date 10/01/2023. Accessed May 2024.
14. Palmetto GBA. Local Coverage Article: Billing and Coding: Guidance for Anti-Inhibitor Coagulant Complex (AICC) National Coverage Determination (NCD) 110.3 (A56065). Centers for Medicare & Medicaid Services Inc. Updated on 11/14/2022 with effective date 11/24/2022. Accessed May 2024.
15. Novitas Solutions, Inc. Local Coverage Article: Billing and Coding: Hemophilia Factor Products (A56433). Centers for Medicare & Medicaid Services Inc. Updated on 09/29/2023 with effective date 10/01/2023. Accessed May 2024.

Appendix 1 – Covered Diagnosis Codes

Appendix 2 – Centers for Medicare and Medicaid Services (CMS)

The preceding information is intended for non-Medicare coverage determinations. Medicare coverage for outpatient (Part B) drugs is outlined in the Medicare Benefit Policy Manual (Pub. 100-2), Chapter 15, §50 Drugs and Biologicals. In addition, National Coverage Determinations (NCDs) and/or Local Coverage Determinations (LCDs) may exist and compliance with these policies is required where applicable. Local Coverage Articles (LCAs) may also exist for claims payment purposes or to clarify benefit eligibility under Part B for drugs which may be self-administered. The following link may be used to search for NCD, LCD, or LCA documents: https://www.cms.gov/medicare-coverage-database/search.aspx. Additional indications, including any preceding information, may be applied at the discretion of the health plan.