Last Review Date: 12/07/2023

Date of Origin: 12/07/2023

Dates Reviewed: 12/2023

1. Length of Authorization ¹

Prophylaxis Therapy

• Coverage will be provided for 6 months and may be renewed annually thereafter.

On-Demand Therapy

• Coverage is provided for 3 months and is eligible for renewal.

Note: The cumulative amount of medication the patient has on-hand, indicated for the acute treatment of TTP events, will be considered for authorizations. The authorization will provide a sufficient quantity in order for the patient to have a cumulative amount of medication on-hand in order to treat up to 4 acute attacks per 4 weeks for the duration of the authorization.

2. Dosing Limits

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

• Adzynma 500 IU single-dose vial for injection:
  • Prophylaxis: 2 vials every other week
  • On-Demand: 2 vials daily for 7 days
• Adzynma 1500 IU single-dose vial for injection: 64764-0135-xx
  • Prophylaxis: 3 vials every other week

1. • • On-Demand: 3 vials on day 1, then 2 vials on day 2 and 1 vial daily for 5 days more.

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

      Prophylaxis Therapy

• 450 billable units every other week

   On-Demand Therapy

• Treatment Day 1: 450 billable units
• Treatment Day 2: 300 billable units
• Treatment Day 3 and beyond: 150 billable units once daily x 5 days more (total of 7 days)

3. Initial Approval Criteria ¹

Coverage is provided in the following conditions:

• Patient is at least 2 years of age; AND
• Patient has not been diagnosed with other cTTP like disorders (e.g., acquired TTP, immune TTP, other primary thrombotic microangiopathies, immune thrombocytopenia-ITP, Evans Syndrome, etc.); AND
• Patient does not have a medical history or the presence of functional ADAMTS13 inhibitors prior to the start of therapy; AND

Universal Criteria ^1-3

• Patient does not have a known sensitivity to hamster protein; AND

Congenital Thrombotic Thrombocytopenic Purpura (cTTP) † Ф ^1-8,10

• Patient has a documented diagnosis of severe hereditary ADAMTS13 deficiency, defined as confirmed by molecular genetic testing, documenting biallelic pathogenic variants in ADAMTS13; AND
• Patient has an ADAMTS13 activity of < 10 % as measured by the fluorescent resonance energy transfer- von Willebrand factor73 (FRETS-VWF73) assay (Note: Patients currently receiving prophylactic plasma infusion therapy may exceed 10% ADAMTS13 activity at start of therapy); AND
  • Treatment will be used as prophylactic therapy; AND
    • Patient has a history of at least one TTP event or is currently receiving prophylactic plasma infusion therapy (Note: Patients who have been receiving prophylactic plasma-based therapies should discontinue routine use of those therapies after achieving a therapeutic response); OR
  • Treatment will be used as on-demand therapy and patient is at risk of a disease exacerbation

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

4. Renewal Criteria ¹

Coverage may be renewed based upon the following criteria:

• Patient continues to meet the universal and other indication-specific relevant criteria identified in section III; AND
• Absence of unacceptable toxicity from the drug. Examples of unacceptable toxicity include: severe hypersensitivity or anaphylactic reactions, etc.; AND
• Patient has responded to therapy compared to pre-treatment baseline with the following:  
  • If symptomatic, improvement in the signs and symptoms of disease (e.g., neurological symptoms including confusion, dysphonia, dysarthria, focal or general motor symptoms, seizures; renal dysfunction, TTP-related pain, etc.); AND

Prophylaxis:

• • Patient has a reduction in or an absence of an acute TTP event, defined by a drop in platelet count (≥50% of baseline or a platelet count <100,000/μL) and an elevation of lactate dehydrogenase (LDH) (>2× baseline or >2× upper limit normal (ULN)); OR
  • Patient has a reduction in or an absence of a sub-acute TTP event, defined by a thrombocytopenia event or a microangiopathic hemolytic anemia event; and organ-specific signs and symptoms including but not limited to renal dysfunction events, neurological symptoms events, fever, fatigue/lethargy, and/or abdominal pain; OR

On-Demand*:

• • Patient has responded to an acute TTP event with therapy as evidenced by improvement in thrombocytopenia (defined as a drop in platelets ≥25% of baseline or a platelet count less than <150,000/mcg/L) or in microangiopathic hemolytic anemia (defined as an elevation of LDH > 1.5 times of baseline or >1.5 times ULN) 

*Note: The cumulative amount of medication the patient has on-hand, indicated for the acute treatment of TTP events, will be considered for authorizations. The authorization will provide a sufficient quantity in order for the patient to have a cumulative amount of medication on-hand in order to treat up to 4 acute attacks per 4 weeks for the duration of the authorization (unless otherwise specified).

5. Dosage/Administration ¹

6. Billing Code/Availability Information

HCPCS code:

• J3590 – Unclassified biologics
• C9167 – Injection, apadamtase alfa, 10 units; 1 billable unit = 10 units (Effective 04/01/2024)

NDC:

• Adzynma 500 IU single-dose vial for injection: 64764-0130-xx
• Adzynma 1500 IU single-dose vial for injection: 64764-0135-xx

7. References

1. Adzynma [package insert]. Lexington, MA; Takeda Pharm. USA, Inc.; November 2023. Accessed November 2023.
2. Asmis, L. M., Serra, A., Krafft, A., Licht, A., Leisinger, E., Henschkowski-Serra, J., et al. 2022. Recombinant ADAMTS13 for Hereditary Thrombotic Thrombocytopenic Purpura. N Engl J Med, 387, 2356-2361.
3. Alwan, F., C. Vendramin, R. Liesner, A. Clark, W. Lester, T. Dutt, W. Thomas, R. Gooding, T. Biss, H. G. Watson, N. Cooper, R. Rayment, T. Cranfield, J. J. van Veen, Q. A. Hill, S. Davis, J. Motwani, N. Bhatnagar, N. Priddee, M. David, M. P. Crowley, J. Alamelu, H. Lyall, J. P. Westwood, M. Thomas and M. Scully (2019). “Characterization and treatment of congenital thrombotic thrombocytopenic purpura.” Blood 133(15): 1644-1651.
4. Sukumar, S., B. Lämmle and S. R. Cataland (2021). “Thrombotic Thrombocytopenic Purpura: Pathophysiology, Diagnosis, and Management.” J Clin Med 10(3): 536.

5. Zheng XL, Vesely SK, Cataland SR, et al. ISTH guidelines for treatment of thrombotic thrombocytopenic purpura. J Thromb Haemost. 2020;18(10):2496-2502. Doi:10.1111/jth.15010.
6. ClinicalTrials.gov. A Phase 3, Prospective, Randomized, Controlled, Open-label, Multicenter, 2 Period Crossover Study With a Single Arm Continuation Evaluating the Safety And Efficacy of BAX 930 (rADAMTS13) in the Prophylactic And On-demand Treatment of Subjects With Severe Congenital Thrombotic Thrombocytopenic Purpura (cTTP, Upshaw-Schulman Syndrome [USS], Hereditary Thrombotic Thrombocytopenic Purpura [hTTP]). https://clinicaltrials.gov/study/NCT03393975?intr=tak-755&rank=4.
7. ClinicalTrials.gov. A Phase 3b, Prospective, Open-label, Multicenter, Single Treatment Arm, Continuation Study of the Safety and Efficacy of TAK-755 (rADAMTS13, Also Known as BAX 930/SHP655) in the Prophylactic and On-demand Treatment of Subjects With Severe Congenital Thrombotic Thrombocytopenic Purpura (cTTP; Upshaw-Schulman Syndrome, or Hereditary Thrombotic Thrombocytopenic Purpura). https://clinicaltrials.gov/study/NCT04683003?intr=tak-755&rank=1.
8. George JN (Oct 2023). Hereditary thrombotic thrombocytopenic purpura (hTTP). Crowther M, Tirnauer JS (Eds.). UpToDate. Accessed November 17, 2023. Available from: https://www.uptodate.com/contents/hereditary-thrombotic-thrombocytopenic-purpura-http?search=ttp&source=search_result&selectedTitle=4~150&usage_type=default&display_rank=4#H329189760.

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.

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