Takhzyro (lanadelumab-flyo) Policy Number: 5.01.675 Last Review: 1/2019 Origination: 1/2019 Next Review: 1/2020 Policy Blue Cross and Blue Shield of Kansas City (Blue KC) will provide coverage for Takhzyro (lanadelumab) when it is determined to be medically necessary because the criteria shown below are met. When Policy Topic is covered Takhzyro (lanadelumab) may be considered medically necessary when all of the following criteria are met: FDA-Approved Indications 1. Hereditary Angioedema (HAE) Due to C1 Inhibitor (C1-INH) Deficiency [Type I or Type II] Prophylaxis, Initial Therapy. Approve Takhzyro for 1 year if the patient meets the following criteria (A and B): A) The patient has HAE type I or type II as confirmed by the following diagnostic criteria (i and ii): i. The patient has low levels of functional C1-INH protein (< 50% of normal) at baseline, as defined by the laboratory reference values [documentation required]; AND ii. The patient has lower than normal serum C4 levels at baseline, as defined by the laboratory reference values [documentation required]; AND B) The medication is prescribed by or in consultation with an allergist/immunologist or a physician that specializes in the treatment of HAE or related disorders. Takhzyro is FDA-approved for routine prophylaxis of attacks of HAE in patients 12 years of age and older. 1 The WAO/EAACI guidelines and an international consensus algorithm note that HAE diagnosis can be confirmed by measuring functional C1-INH protein levels (usually < 50% of normal in patients with HAE), C4 levels, and C1-INH antigenic levels. 2-3,8 Patients with HAE type I have low C4 and C1- INH antigenic protein levels, along with low levels of functional C1-INH protein. 2 Patients with HAE type
II have low C4 and functional C1-INH protein level, with a normal or elevated C1- INH antigenic protein level. C1-INH replacement therapies are appropriate for both HAE type I and type II. Patients with the third type of HAE, previously referred to as HAE type III, have normal C4 and C1-INH antigenic protein levels. 2. Hereditary Angioedema (HAE) Due to C1 Inhibitor (C1-INH) Deficiency [Type I or Type II] Patients Currently Receiving Takhzyro Prophylactic Therapy. Approve Takhzyro for 1 year if the patient meets all of the following criteria (A, B, and C): A) The patient is currently receiving Takhzyro for HAE type I or type II prophylaxis [documentation required to confirm HAE type I or type II diagnosis]; AND B) According to the prescribing physician, the patient has had a favorable clinical response (e.g., decrease in number of HAE acute attack frequency, decrease in HAE attack severity, decrease in duration of HAE attacks) since initiating Takhzyro prophylactic therapy compared with baseline (i.e., prior to initiating prophylactic therapy); AND C) The medication is prescribed by or in consultation with an allergist/immunologist or a physician that specializes in the treatment of HAE or related disorders. Drug must be sourced from an approved specialty pharmacy provider. When Policy Topic is not covered Takhzyro (lanadelumab) is considered not medically necessary when the above criteria is not met and investigational for all other uses, including: 1. Concomitant Use with Other HAE Prophylactic Therapies (e.g., Cinryze, Haegarda ). Takhzyro has not been studied in combination with other prophylactic therapies for HAE, and combination therapy for long-term prophylactic use is not recommended. Patients may use other medications, including Cinryze, for on-demand treatment of acute HAE attacks, and for short-term (procedural) prophylaxis. 2. Coverage is not recommended for circumstances not listed in the Recommended Authorization Criteria. Criteria will be updated as new published data are available. Considerations Takhzyro (lanadelumab) requires prior authorization through the Clinical Pharmacy Department. This Blue Cross and Blue Shield of Kansas City policy statement was developed using available resources such as, but not limited to: Food and Drug Administration (FDA) approvals, Facts and Comparisons, National specialty guidelines, local medical policies of other health plans, Medicare (CMS), local providers.
Description of Procedure or Service Takhzyro is a human monoclonal antibody inhibitor of plasma kallikrein indicated for prophylaxis to prevent attacks of hereditary angioedema (HAE) in patients 12 years and older. 1 HAE is characterized by recurrent episodes of non-pruritic, non-pitting, subcutaneous or submucosal edema associated with pain syndrome, nausea, vomiting, diarrhea, and/or life-threatening airway swelling. 2 A consensus document published by an international expert panel on HAE diagnosis and treatment notes there are two categories of HAE: HAE due to C1 esterase inhibitor (C1-INH) deficiency and HAE with normal C1-INH. HAE due to C1-INH deficiency has two subtypes: type I HAE characterized by low C1-INH antigen and function; and type II HAE with normal C1-INH antigen but low C1-INH function. 3 A third type, previously called type III HAE but now referred to as HAE with normal C1-INH, occurs in patients with normal C1-INH function; the exact cause has not been determined. There is a wide variation in the frequency and severity of attacks for all types of HAE. Clinical experience suggests that minor trauma and/or stress, among other triggers, may precipitate attacks. Untreated attacks typically last over 48 to 96 hours. There are no randomized or controlled clinical trial data available with any therapy for use in HAE with normal C1-INH. 4,5 Until data from randomized controlled studies become available, no firm recommendations regarding the treatment of HAE with normal C1-INH can be made. Guidelines The World Allergy Organization (WAO) and European Academy of Allergy and Clinical Immunology (EAACI) revised and updated guidelines (2017) for the management of HAE in patients throughout the world. 3 Long-term prophylaxis should be considered in patients based on the severity of the disease, frequency of attacks, the patient s quality of life, availability of resources, and the failure to achieve adequate control by appropriate on-demand therapy. As these factors can vary over time, all patients should be evaluated for long-term prophylaxis at every visit, at least annually. C1-INH concentrate is first-line for long-term prophylaxis. The use of androgens for long-term prophylaxis may be considered as second-line but should be considered critically due to potential for adverse events. A practice parameter update from a Joint Task Force (2013) has similar recommendations. 6 Treatment with low-to-moderate doses of anabolic androgens are noted to provide effective and relatively safe long-term HAE prophylaxis for many patients. Treatment with antifibrinolytic agents are noted as being generally less effective than androgens, and treatment with plasma-derived C1-INH replacement therapies are considered effective and safe for long-term prophylaxis. Plasma-derived C1-INH replacement therapies are the preferred agents for longterm prophylaxis during pregnancy.
The US Hereditary Angioedema Association Medical Advisory Board published recommendations (2013) for the management of HAE due to C1-INH deficiency. 7 As per the Advisory Board, there are no rigid criteria to meet for long-term prophylaxis; the decision should reflect the needs of the individual patient by taking into consideration attack frequency, severity, other comorbid conditions, access to emergency medical services, patient experience, and preference. The recommendations note that although anabolic androgens have been used for prophylaxis for a long time, they have dose-related adverse events which may be significant. Anabolic androgens should not be used in patients < 16 years of age and in pregnant or breastfeeding women. They should also be discontinued if the patient is not tolerating the adverse events. The Advisory Board s position is that anabolic androgens should not be used in patients who have a preference for alternative therapy and that patients should not be required to fail anabolic androgen therapy as a prerequisite to receiving prophylactic C1-INH therapy. Plasma-derived C1-INH therapy has been proven to be effective and safe for longterm prophylactic therapy; however, repeated intravenous administration can result in loss of readily accessible veins. Although indwelling ports have been used, the Medical Advisory Board discourages the use of indwelling ports, unless it is medically necessary, due to the risk of thrombosis and infection. Other agents that are used off-label for prophylactic therapy are anabolic androgens such as oxandrolone and methyltestosterone and antifibrinolytics such as aminocaproic acid and tranexamic acid. The guidelines have not been updated to include Takhzyro for prophylaxis of HAE attacks. Rationale Prior authorization is required to ensure the safe, clinically appropriate and cost effective use of Takhzyro (lanadelumab) while maintaining optimal therapeutic outcomes. References 1. Takhzyro for subcutaneous injection [prescribing information]. Lexington, MA: Shire; August 2018. 2. Bowen T, Cicardi M, Farkas H, et al. 2010 international consensus algorithm for the diagnosis, therapy and management of hereditary angioedema. Ann Allergy Asthma Immunol. 2010;6:24. 3. Mauer M, Magerl M, Ansotegui I, et al. The international WAO/EAACI guideline for the management of hereditary angioedema the 2017 revision and update. Allergy. 2018;73(8):1575-1596. Available at: https://onlinelibrary.wiley.com/doi/epdf/10.1111/all.13384. Accessed on September 4, 2018. 4. 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:S145-S156.
5. Magerl M, Germenis AE, Maas C, et al. Hereditary angioedema with normal C1 inhibitor. Update on evaluation and treatment. Immunol Allergy Clin N Am. 2017;37:571-584. 6. Zuraw BL, Bernstein JA, Lang DM. A focused parameter update: Hereditary angioedema, acquired C1 inhibitor deficiency, and angiotensin-converting enzyme inhibitor-associated angioedema. J Allergy Clin Immunol. 2013;131(6):1491-1493.e25. 7. 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: In Practice. 2013;1:458-467. Available at: https://haei.org/wp-content/uploads/2015/04/zuraw-b-l-us-haea-mab-2013- Recommendations.pdf. Accessed on July 26, 2018. 8. Wagenaar-Bos IGA, Drouet C, Aygoren-Pursun E, et al. Functional C1-inhibitor diagnostics in hereditary angioedema: assay evaluation and recommendations. J Immunol. Methods. 2008;338:14-20. Billing Coding/Physician Documentation Information N/A Pharmacy benefit; specialty pharmacy sourcing Additional Policy Key Words N/A Policy Implementation/Update Information 01/2019 New policy titled Takhzyro (lanadelumab) State and Federal mandates and health plan contract language, including specific provisions/exclusions, take precedence over Medical Policy and must be considered first in determining eligibility for coverage. The medical policies contained herein are for informational purposes. The medical policies do not constitute medical advice or medical care. Treating health care providers are independent contractors and are neither employees nor agents Blue KC and are solely responsible for diagnosis, treatment and medical advice. No part of this publication may be reproduced, stored in a retrieval system or transmitted, in any form or by any means, electronic, photocopying, or otherwise, without permission from Blue KC.