BlueCross BlueShield of Tennessee Medical Policy Manual

Lanadelumab-flyo (Takhzyro®)

MPORTANT REMINDER

We develop Medical Policies to provide guidance to Members and Providers.  This Medical Policy relates only to the services or supplies described in it.  The existence of a Medical Policy is not an authorization, certification, explanation of benefits or a contract for the service (or supply) that is referenced in the Medical Policy.  For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed.  If there is a conflict between the medical policy and a health plan or government program (e.g., TennCare), the express terms of the health plan or government program will govern.

POLICY         

INDICATIONS

The indications below including FDA-approved indications and compendial uses are considered a covered benefit provided that all the approval criteria are met and the member has no exclusions to the prescribed therapy.

FDA-Approved Indications

Takhzyro is indicated for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adult and pediatric patients aged 2 years and older.

All other indications are considered experimental/investigational and not medically necessary.

DOCUMENTATION

Submission of the following information is necessary to initiate the prior authorization review:

• For initial authorization, the following should be documented:

• C1 inhibitor functional and antigenic protein levels
• F12, angiopoietin-1, plasminogen, kininogen-1 (KNG1), heparan sulfate-glucosamine 3-O-sulfotransferase 6 (HS3ST6), or myoferlin (MYOF) gene mutation testing, if applicable
• Chart notes confirming family history of angioedema and the angioedema was refractory to a trial of high-dose antihistamine therapy, if applicable

• For continuation of therapy, chart notes demonstrating a reduction in frequency of attacks

PRESCRIBER SPECIALTIES

This medication must be prescribed by or in consultation with a prescriber who specializes in the management of HAE.

COVERAGE CRITERIA

Hereditary Angioedema (HAE)

Authorization of 12 months may be granted for prevention of hereditary angioedema attacks when the requested medication will not be used in combination with any other medication used for the prophylaxis of HAE attacks and both of the following criteria are met at the time of diagnosis:

• Member meets either of the following criteria:

• Member has C1 inhibitor deficiency or dysfunction as confirmed by laboratory testing and meets one of the following criteria:

• C1 inhibitor (C1-INH) antigenic level below the lower limit of normal as defined by the laboratory performing the test, or
• Normal C1-INH antigenic level and a low C1-INH functional level (functional C1-INH less than 50% or C1-INH functional level below the lower limit of normal as defined by the laboratory performing the test).

• Member has normal C1 inhibitor as confirmed by laboratory testing and meets one of the following criteria:

• Member has an F12, angiopoietin-1, plasminogen, kininogen-1 (KNG1), heparan sulfate-glucosamine 3-O-sulfotransferase 6 (HS3ST6), or myoferlin (MYOF) gene mutation as confirmed by genetic testing, or
• Member has a documented family history of angioedema and the angioedema was refractory to a trial of high-dose antihistamine therapy (i.e., cetirizine at 40 mg per day or the equivalent) for at least one month.

• Other causes of angioedema have been ruled out (e.g., angiotensin-converting enzyme inhibitor [ACE-I] induced angioedema, angioedema related to an estrogen-containing drug, allergic angioedema).

CONTINUATION OF THERAPY  

Authorization of 12 months may be granted for continuation of therapy when all of the following criteria are met:

• Member meets all requirements in the coverage criteria section.
• Member has experienced a significant reduction in frequency of attacks (e.g., ≥ 50%) since starting treatment.
• Member has reduced the use of medications to treat acute attacks since starting treatment.
• The requested drug is being dosed every 4 weeks or dosing every 4 weeks has been considered if the member is well-controlled on therapy for more than 6 months.

APPLICABLE TENNESSEE STATE MANDATE REQUIREMENTS

BlueCross BlueShield of Tennessee’s Medical Policy complies with Tennessee Code Annotated Section 56-7-2352 regarding coverage of off-label indications of Food and Drug Administration (FDA) approved drugs when the off-label use is recognized in one of the statutorily recognized standard reference compendia or in the published peer-reviewed medical literature.

ADDITIONAL INFORMATION 

For appropriate chemotherapy regimens, dosage information, contraindications, precautions, warnings, and monitoring information, please refer to one of the standard reference compendia (e.g., the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) published by the National Comprehensive Cancer Network®, Drugdex Evaluations of Micromedex Solutions at Truven Health, or The American Hospital Formulary Service Drug Information).

REFERENCES

1. Takhzyro [package insert]. Lexington, MA: Dyax Corp., a Takeda company; February 2023.
2. Maurer M, Magerl M, Ansotegui I, et al. The international WAO/EAACI guideline for the management of hereditary angioedema – the 2021 revision and update. Allergy. 2022 Jan 10. doi: 10.1111/all. 15214. Online ahead of print.
3. Henao MP, Kraschnewski J, Kelbel T, Craig T. Diagnosis and screening of patients with hereditary angioedema in primary care. Therapeutics and Clin Risk Management. 2016; 12: 701-711.
4. Bernstein, J.  Severity of Hereditary Angioedema, Prevalence, and Diagnostic Considerations.  Am J Med. 2018:24;292-298.
5. 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: In Practice. 2021 Jan;9(1):132-150.e3.
6. Sharma J, Jindal AK, Banday AZ, et al. Pathophysiology of Hereditary Angioedema (HAE) Beyond the SERPING1 Gene [published online ahead of print, 2021 Jan 14] [published correction appears in Clin Rev Allergy Immunol. 2021 Feb 17]. Clin Rev Allergy Immunol. 2021;10.1007/s12016-021-08835-8. Doi:10.1007/s12016-021-08835-8.
7. Kanani, A., Schellenberg, R. & Warrington, R. Urticaria and angioedema. All Asth Clin Immun 7, S9 (2011), Table 2.
8. Veronez CL, Csuka D, Sheik FR, et al. The expanding spectrum of mutations in hereditary angioedema. J Allergy Clin Immunol Pract. 2021;S2213-2198(21)00312-3.

ORIGINAL EFFECTIVE DATE: 1/31/2019

MOST RECENT REVIEW DATE: 7/1/2025

ID_CHS

Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.

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