Last Review Date: 08/01/2024

Date of Origin: 08/1/2017

Dates Reviewed: 08/2017, 12/2017, 03/2018, 06/2018, 10/2018, 10/2019, 03/2020, 10/2020, 10/2021, 10/2022, 10/2023, 08/2024

1. Length of Authorization

Coverage will be provided for 12 months and may be renewed.

2. Dosing Limits

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

• Haegarda 2000 IU single-dose vial kit: 16 kits per 28 days
• Haegarda 3000 IU single-dose vial kit: 8 kits per 28 days

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

• 5,600 billable units per 28 days

3. Initial Approval Criteria ¹

Coverage is provided in the following conditions:

• Patient is at least 6 years of age; AND

Universal Criteria ^{1,13,18, 20}

• Must be prescribed by, or in consultation with, a specialist in: allergy, immunology, hematology, pulmonology, or medical genetics; AND
• Will not be used in combination with other prophylactic therapies targeting C1 inhibitor (i.e., Cinryze) or kallikrein (i.e., Takhzyro or Orladeyo); AND
• Confirmation the patient is avoiding the following possible triggers for HAE attacks:

• Estrogen-containing oral contraceptive agents AND hormone replacement therapy; AND
• Antihypertensive agents containing ACE inhibitors or angiotensin II receptor blockers (ARBs); AND
• Dipeptidyl peptidase IV (DPP-IV) inhibitors (e.g., sitagliptin, etc.); AND
• Neprilysin inhibitors (e.g., sacubitril); AND

Prophylaxis to Prevent Hereditary Angioedema (HAE) Attacks † Ф ^{1,3,13,18,19,20}

• Patient has a history of one of the following criteria for long-term HAE prophylaxis:

• History of at least three (3) severe HAE attack per month (i.e., airway swelling, debilitating cutaneous or gastrointestinal episodes)
• Patient is disabled more than 5 days per month by HAE
• History of at least one laryngeal attack caused by HAE; AND

• Treatment with “on-demand” therapy (i.e., Kalbitor, Firazyr, Ruconest, or Berinert) did not provide satisfactory control or access to “on-demand therapy” is limited; AND
• Patient has one of the following clinical presentations consistent with a HAE subtype§, which must be confirmed by repeat blood testing (treatment for acute attack should not be delayed for confirmatory testing):

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

4. Renewal Criteria^{1,13,18,19,20}

Coverage can 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 the following: severe hypersensitivity reactions, thromboembolic events, etc.; AND
• Significant improvement in severity, frequency, and/or duration of attacks have been achieved and sustained

5. Dosage/Administration¹

   Indication	Dose
   Prophylaxis to Prevent Hereditary Angioedema (HAE) attacks	60 IU/kg body weight injected subcutaneously twice weekly (every 3 or 4 days) **Note: Patients may self-administer Haegarda after being instructed by their healthcare provider.

6. Billing Code/Availability Information

HCPCS Code:

• J0599 - Injection, c-1 esterase inhibitor (human), (haegarda), 10 units; 1 billable unit = 10 IU

NDC(s):

• Haegarda 2000 IU single-dose vial kit: 63833-0828-xx
• Haegarda 3000 IU single-dose vial kit: 63833-0829-xx

7. References

1. Haegarda [package insert]. Kankakee, IL; CSL Behring LLC; January 2022. Accessed June 2024.
2. Longhurst H, Cicardi M, Craig T, et al.; COMPACT Investigators. Prevention of hereditary angioedema attacks with a subcutaneous C1 inhibitor. N Eng J Med. 2017;376:1131-1140.
3. Bowen T, Cicardi M, Farkas H, et al. Canadian 2003 International Consensus Algorithm For the Diagnosis, Therapy, and Management of Hereditary Angioedema. J Allergy Clin Immunol. 2004 Sep;114(3):629-37.
4. Bygum A, Andersen KE, Mikkelsen CS. Self-administration of intravenous C1-inhibitor therapy for hereditary angioedema and associated quality of life benefits. Eur J Dermatol. Mar-Apr 2009;19(2):147-151.
5. Bowen T, Cicardi M, Farkas H, et al. 2010 International consensus algorithm for the diagnosis, therapy and management of hereditary angioedema. Allergy Asthma Clin Immunol. 2010;6(1):24.
6. Craig T, Aygören-Pürsün E, Bork K, et al. WAO Guideline for the Management of Hereditary Angioedema. World Allergy Organ J. 2012 Dec;5(12):182-99.
7. Gompels MM, Lock RJ, Abinun M, et al. C1 inhibitor deficiency: consensus document.  Clin Exp Immunol. 2005;139(3):379.
8. Betschel S, Badiou J, Binkley K, et al. Canadian hereditary angioedema guideline. Asthma Clin Immunol. 2014 Oct 24;10(1):50. doi: 10.1186/1710-1492-10-50.
9. Zuraw BL, Bernstein JA, Lang DM, et al. A focused parameter update: hereditary angioedema, acquired C1 inhibitor deficiency, and angiotensin-converting enzyme inhibitor-associated angioedema. J Allergy Clin Immunol. 2013 Jun;131(6):1491-3. doi: 10.1016/j.jaci.2013.03.034.
10. Zuraw BL, Banerji A, Bernstein JA, et al. US Hereditary Angioedema Association Medical Advisory Board 2013 recommendations for the management of hereditary angioedema due to C1 inhibitor deficiency. J Allergy Clin Immunol Pract. 2013 Sep-Oct;1(5):458-67.
11. Frank MM, Zuraw B, Banerji A, et al. Management of children with Hereditary Angioedema due to C1 Inhibitor deficiency. Pediatrics. 2016 Nov. 135(5)
12. Zuraw BL, Bork K, Binkley KE, et al. Hereditary angioedema with normal C1 inhibitor function: Consensus of an international expert panel. Allergy Asthma Proc. 2012;33 Suppl 1:145-156.
13. Maurer M, Mager M, Ansotegui I, et al. The international WAO/EAACI guideline for the management of hereditary angioedema-The 2017 revision and update. Allergy. 2018 Jan 10. doi: 10.1111/all.13384.
14. Lang DM, Aberer W, Bernstein JA, et al. International consensus on hereditary and acquired angioedema. Ann Alergy Asthma Immunol. 2012;109:395-402.
15. Wintenberger C, Boccon-Gibod I, Launay D, et al. Tranexamic acid as maintenance treatment for non-histaminergic angioedema: analysis of efficacy and safety in 37 patients. Clin Exp Immunol. 2014 Oct; 178(1): 112–117.
16. Saule C, Boccon-Gibod I, Fain O, et al. Benefits of progestin contraception in non-allergic angioedema. Clin Exp Allergy. 2013 Apr;43(4):475-82.
17. Frank MM, Sergent JS, Kane MA, et al. Epsilon aminocaproic acid therapy of hereditary angioneurotic edema; a double-blind study. N Engl J Med. 1972:286:808-812.
18. Betschel S, Badiou J, Binkley K, et al. The International/Canadian Hereditary Angioedema Guideline. Allergy Asthma Clin Immunol. 2019; 15: 72. Published online 2019 Nov 25.  doi: 10.1186/s13223-019-0376-8.
19. Busse PJ, Christiansen SC, Riedl MA, et al. US HAEA Medical Advisory Board 2020 Guidelines for the Management of Hereditary Angioedema. J Allergy Clin Immunol Pract. 2021 Jan;9(1):132-150.e3. doi: 10.1016/j.jaip.2020.08.046.
20. Maurer M, Magerl M, Betschel S, et al. The international WAO/EAACI guideline for the management of hereditary angioedema – The 2021 revision and update. Allergy. 2021 Nov 22. doi: 10.1111/all.15214.

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/LCD/LCA): N/A