Last Review Date: 11/05/2024

Date of Origin: 11/05/2024

Dates Reviewed: 11/2024

1. Length of Authorization

Coverage will be provided for 6 months and may be renewed every 12 months thereafter.

2. Dosing Limits

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

• 300 mg every week

3. Initial Approval Criteria ^1-3,8,10-11

Coverage is provided in the following conditions:

• Patient is at least 12 years of age; AND
• Patient will initiate maintenance therapy at the lower range of dosing (i.e., 150 mg every week); AND
• Will not be used for the treatment of breakthrough bleeds (Note: Factor VIII or Factor IX products may be administered on an as needed basis for the treatment of breakthrough bleeds in patients being treated with marstacimab); AND
• Female patients of reproductive potential are not pregnant prior to initiating therapy with marstacimab; AND

Universal Criteria

• Will not be used in combination with clotting factor products (i.e., factor VIII or factor IX concentrates) as prophylactic therapy – Therapy can be initiated at any time after discontinuing clotting factor concentrates (Note: factor VIII or factor IX products can be administered for the treatment of breakthrough bleeds while receiving marstacimab); AND

Hemophilia A (congenital factor VIII deficiency) without inhibitors † Ф

• Diagnosis of congenital factor VIII deficiency has been confirmed by blood coagulation testing; AND
• Must be used for routine prophylaxis to prevent or reduce the frequency of bleeding episodes; AND
• Used as treatment in one of the following:
  • • Primary prophylaxis in patients with severe factor VIII deficiency (factor VIII level of <1%); OR
    • Secondary prophylaxis in patients with at least TWO documented episodes of spontaneous bleeding into joints;

Hemophilia B (congenital factor IX deficiency aka Christmas Disease) without inhibitors † Ф

• Diagnosis of congenital factor IX deficiency has been confirmed by blood coagulation testing; AND
• Must be used for routine prophylaxis to prevent or reduce the frequency of bleeding episodes; AND
• Used as treatment in one of the following:
  • • Primary prophylaxis in patients with severe factor IX deficiency (factor IX level of <1%); OR
    • Secondary prophylaxis in patients with at least TWO documented episodes of spontaneous bleeding into joints;

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

4. Renewal Criteria ^1-3,8

Coverage can be renewed based upon the following criteria:

• Patient continues to meet the indication-specific relevant criteria such as concomitant therapy requirements (not including prerequisite therapy), performance status, etc. identified in section III; AND
• Absence of unacceptable toxicity from the drug. Examples of unacceptable toxicity include: thromboembolic events, hypersensitivity, etc.; AND
  • Patient has demonstrated a beneficial response to therapy (i.e., the frequency of bleeding episodes has decreased from pre-treatment baseline); OR
  • Patient requires a dose escalation* (up to the maximum dose and frequency specified below) provided that the patient meets all the following criteria:
    • Patient weighs greater than or equal to 50 kg
    • Control of bleeding events has been inadequate (i.e., patient has experienced two or more breakthrough bleeds while on maintenance therapy at the lower dose)
    • Patient has been fully adherent to maintenance therapy for at least six months at the lower dose

*Note: Safety and efficacy of Hympavzi at doses above 300 mg weekly has not been established.

5. Dosage/Administration ¹

6. Billing Code/Availability Information

HCPCS Code:

• J3590 – Unclassified biologic

NDC:

• Hympavzi single-dose prefilled syringe: 00069-1510-xx
• Hympavzi single-dose prefilled pen: 00069-2151-xx

7. References

1. Hympavzi [package insert]. New York, NY; Pfizer, Inc. October 2024. Accessed October 2024.
2. MASAC Recommendations Concerning Products Licensed for the Treatment of Hemophilia and Selected Disorders of the Coagulation System. Revised April 11, 2024. National Hemophilia Foundation. MASAC Document #284; April 2024. Available at: https://www.bleeding.org. Accessed May 2024.
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 2024.
4. Annual Review of Factor Replacement Products. Oklahoma Health Care Authority Review Board. Updated Dec 2020. Accessed May 2024.
5. Graham A1, Jaworski K. Pharmacokinetic analysis of anti-hemophilic factor in the obese patient. Haemophilia. 2014 Mar;20(2):226-9.
6. Croteau SE1, Neufeld EJ. Transition considerations for extended half-life factor products. Haemophilia. 2015 May;21(3):285-8.
7. 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).
8. MASAC Recommendation Concerning Prophylaxis for Hemophilia A and B with and without Inhibitors. Revised April 27, 2022. National Hemophilia Foundation.  MASAC Document #267; April 2022. Available at: https://www.bleeding.org. Accessed May 2024.
9. UKHCDO protocol for first line immune tolerance induction for children with severe haemophilia A: A protocol from the UKHCDO Inhibitor and Paediatric Working Parties. 2017. Available at: http://www.ukhcdo.org/guidelines. Accessed May 2024.
10. Hoots, WK. (2024). Hemophilia A and B: Routine management including prophylaxis. In Leung LLK, Tirnauer JS (Eds.), UptoDate. Last updated: April 16, 2024. Accessed May 13, 2024. Available from https://www.uptodate.com/contents/hemophilia-a-and-b-routine-management-including-prophylaxis?search=hemophilia%20a&source=search_result&selectedTitle=2~150&usage_type=default&display_rank=2#H978189854.
11. Matino D, Acharya S, Palladino A, et al. Efficacy and Safety of the Anti-Tissue Factor Pathway Inhibitor Marstacimab in Participants with Severe Hemophilia without Inhibitors: Results from the Phase 3 Basis Trial. Blood, Volume 142, Supplement 1, 2023, Page 285, ISSN 0006-4971, https://doi.org/10.1182/blood-2023-181263.

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.