Last Review Date: 06/01/2023

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, 02/2020, 06/2021, 06/2022, 06/2023

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

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

• Tretten 2,000-3,125 IU vial: 2 vials per 28-day supply

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

• 4,025 billable units per 28-day supply

3. Initial Approval Criteria ^1-3,7

Coverage is provided in the following conditions:

Congenital Factor XIII A-subunit deficiency † Ф

• Diagnosis of congenital factor XIII A-subunit deficiency has been confirmed by blood coagulation testing; AND
• Used for routine prophylaxis of bleeding

† 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 ^1-3,7

Coverage may be renewed based upon the following criteria:

• Patient continues to meet indication-specific relevant criteria identified in section III; AND
• Absence of unacceptable toxicity from the drug. Examples of unacceptable toxicity include: symptoms of allergic-anaphylactic reactions (anaphylaxis, dyspnea, rash, urticaria, tightness of the chest, hypotension, etc.), thromboembolic events (thromboembolism, pulmonary embolism), 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

Routine prophylaxis 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 ^1-3

7. Billing Code/Availability Information

HCPCS Code & NDC:

8. References

1. Tretten [package insert]. Bagsvaerd, Denmark; Novo Nordisk; June 2020. Accessed May 2023.
2. MASAC Recommendations Concerning Products Licensed for the Treatment of Hemophilia and Other Bleeding Disorders. 2022 National Hemophilia Foundation. MASAC Document #272; April 2022. Available at: http://www.hemophilia.org. Accessed May 2023.
3. Guidelines for the Management of Hemophilia. 3^rd Edition. World Federation of Hemophilia 2020. Available at: https://www1.wfh.org/publications/files/pdf-1863.pdf. Accessed May 2023.
4. Graham A1, Jaworski K. Pharmacokinetic analysis of anti-hemophilic factor in the obese patient. Haemophilia. 2014 Mar;20(2):226-9.
5. Croteau SE1, Neufeld EJ. Transition considerations for extended half-life factor products. Haemophilia. 2015 May;21(3):285-8.
6. 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).
7. MASAC Recommendation Concerning Prophylaxis for Hemophilia A and B with and without Inhibitors. 2022 National Hemophilia Foundation.  MASAC Document #267; April 2022. Available at: http://www.hemophilia.org. Accessed May 2023.
8. Rayment R, Chalmers E, Forsyth K, et al. Guidelines on the use of prophylactic factor replacement for children and adults with Haemophilia A and B. B J Haem:190;5,Sep2020. https://doi.org/10.1111/bjh.16704. Accessed May 2023.
9. 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 11/24/2022 with effective date 01/01/2022. Accessed May 2023.
10. Novitas Solutions, Inc. Local Coverage Article: Billing and Coding: Hemophilia Factor Products (A56433). Centers for Medicare & Medicaid Services Inc. Updated on 10/20/2022 with effective date 10/01/2022. Accessed May 2023.

Appendix 1 – Covered Diagnosis Codes

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

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 Determination (NCD), Local Coverage Articles (LCAs) and Local Coverage Determinations (LCDs) may exist and compliance with these policies is required where applicable. They can be found at https://www.cms.gov/medicare-coverage-database/search.aspx. Additional indications may be covered at the discretion of the health plan.

Medicare Part B Covered Diagnosis Codes (applicable to existing NCD/LCA/LCD):