Last Review Date: 08/01/2024

Date of Origin:  08/27/2013

Dates Reviewed:  06/2014, 09/2014, 07/2015, 07/2016, 12/2016, 03/2017, 06/2017, 09/2017, 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 weeks and is eligible for renewal.

The cumulative amount of medication(s) the patient has on-hand, indicated for the acute treatment of HAE, will be taken into account when authorizing. The authorization will provide a sufficient quantity in order for the patient to have a cumulative amount of HAE medication(s) on-hand in order to treat up to 4 acute attacks per 4 weeks for the duration of the authorization.

2. Dosing Limits

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

• Firazyr 30 mg single-dose prefilled syringes for injection: 12 injections per 28 days

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

• 360 billable units per 28 days

3. Initial Approval Criteria ¹

Coverage is provided in the following conditions:

• Patient is at least 18 years of age; AND

Universal Criteria ^1,13,18

• Must be prescribed by, or in consultation with, a specialist in allergy, immunology, hematology, pulmonology, or medical genetics; 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); AND
• Neprilysin inhibitors (e.g., sacubitril); AND

Treatment of acute attacks of Hereditary Angioedema (HAE) † Ф ^{1,13,18,19,21}

• Patient has a history of moderate to severe cutaneous attacks (without concomitant urticaria) OR abdominal attacks OR mild to severe airway swelling attacks of HAE (i.e. debilitating cutaneous/gastrointestinal symptoms OR laryngeal/pharyngeal/tongue swelling); 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

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

• Significant improvement in severity and duration of attacks have been achieved and sustained; AND
• Absence of unacceptable toxicity from the drug. Examples of unacceptable toxicity include the following: laryngeal HAE attacks, etc.; AND
• The cumulative amount of medication(s) the patient has on-hand, indicated for the acute treatment of HAE, will be taken into account when authorizing. The authorization will provide a sufficient quantity in order for the patient to have a cumulative amount of HAE medication(s) on-hand in order to treat up to 4 acute attacks per 4 weeks for the duration of the authorization.

5. Dosage/Administration ¹

   Indication	Dose
   Treatment of Acute Hereditary Angioedema (HAE) attacks	Administer 30 mg subcutaneously in the abdominal area. May be repeated every 6 hours up to a total of 3 doses (90 mg) in 24 hours. **Note: Patients may self-administer Firazyr upon recognition of symptoms of an HAE attack after being instructed by their healthcare provider.

6. Billing Code/Availability Information

     HCPCS Code:

• J1744 – Injection, icatibant, 1 mg; 1 billable unit = 1 mg

NDC:

• Firazyr* 30 mg single-dose prefilled syringe (carton of 1 or 3): 54092-0702-xx

*Generics available from numerous manufacturers

7. References

1. Firazyr [package insert]. Lexington, MA; Takeda Pharmaceuticals America, Inc.; January 2024. Accessed July 2024.
2. Cicardi M, Banerji A, Bracho F, et al, "Icatibant, A New Bradykinin-Receptor Antagonist in Hereditary Angioedema," N Engl J Med, 2010, 363(6):532-41.
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. doi: 10.1016/j.jaip.2013.07.002.OFrank MM, Zuraw B, Banerji A, et al. Management of children with Hereditary Angioedema due to C1 Inhibitor deficiency. Pediatrics. 2016 Nov. 135(5)
11. 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.
12. 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.
13. Lang DM, Aberer W, Bernstein JA, et al. International consensus on hereditary and acquired angioedema. Ann Allergy Asthma Immunol. 2012;109:395-402.
14. 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.
15. 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.
16. 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.
17. 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.
18. 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.
19. Lumry WR, Li HH, Levy RJ, et al. Randomized placebo-controlled trial of the bradykinin B₂ receptor antagonist icatibant for the treatment of acute attacks of hereditary angioedema: the FAST-3 trial. Ann Allergy Asthma Immunol. 2011 Dec;107(6):529-37. doi: 10.1016/j.anai.2011.08.015.
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