CurrentCignaPolicy IP0334

Hereditary Angioedema - Takhzyro

This Cigna Coverage Policy governs prior authorization, coverage criteria, dosing, and exclusions for Takhzyro (lanadelumab-flyo) used as prophylaxis for hereditary angioedema (HAE) due to C1 inhibitor deficiency, and applies to health benefit plans administered by Cigna Companies.

Policy Summary

PayerCigna

PolicyHereditary Angioedema - Takhzyro

Policy CodePolicy IP0334

Change TypeCriteria refinement and prescriber requirement addedgenetic testing requirement removed

Effective DateThe policy effective date is in force until updated or retired

Next Review Date

Key ActionObtain prior authorization and document baseline functional C1‑INH <50% and low serum C4 (or report favorable response for continuation) with prescriber specialty noted.

SourceLink

POLICY UPDATE CHANGES

Removed requirement for confirmed pathogenic variant in SERPING1, F12, ANGPT1, PLG, or KNG1 genes.

Removed explicit requirement for low C1-INH antigenic levels (less than 50%) at baseline wording; replaced with functional C1-INH <50% requirement.

Added a continuation/currently receiving criteria pathway for patients already on Takhzyro and allows 1-year approvals if continuation criteria met.

Added requirement that prescriber be an allergist/immunologist or physician who specializes in treatment of HAE or related disorders.

Policy title updated from 'Hereditary Angioedema - Lanadelumab-flyo' to 'Hereditary Angioedema - Takhzyro' and indication name clarified to 'Due to C1 Inhibitor (C1-INH) Deficiency'.

1 yearstandard approval duration when criteria met

≥2FDA-indicated minimum age for prophylaxis

300 mgstandard adult dose (≥12 years)

J0593HCPCS code for lanadelumab-flyo

Coverage Criteria for Takhzyro (lanadelumab-flyo)

FDA-Approved Indication: HAE Due to C1-INH Deficiency - Prophylaxis

Approve Takhzyro for up to 1 year if the patient meets ONE of the following (A or B):

Approval pathways: Either Initial therapy OR Current therapy continuation

A. Initial therapy: Patient has HAE type I or II as confirmed by diagnostic criteria AND medication is prescribed by or in consultation with an allergist/immunologist or physician who specializes in treatment of HAE or related disorders.

Diagnosis of HAE with normal C1-INH (HAE type III) does NOT satisfy requirement.

A.i Diagnostic criteria for HAE type I/II: a. Patient has low levels of functional C1-INH protein (< 50% of normal) at baseline [documentation required]; AND b. Patient has lower than normal serum C4 levels at baseline [documentation required].functional C1-INH <50%

Policy Summary

PayerCigna

PolicyHereditary Angioedema - Takhzyro

Policy CodePolicy IP0334

Change TypeCriteria refinement and prescriber requirement addedgenetic testing requirement removed

Effective DateThe policy effective date is in force until updated or retired

Next Review Date

Key ActionObtain prior authorization and document baseline functional C1‑INH <50% and low serum C4 (or report favorable response for continuation) with prescriber specialty noted.

SourceLink

On This Page

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B. Continuation (patient currently receiving Takhzyro): i. Patient has diagnosis of HAE type I or II [documentation required]; AND ii. Prescriber reports favorable clinical response since initiating Takhzyro (e.g., decreased attack frequency, severity, or duration); AND iii. Medication is prescribed by or in consultation with an allergist/immunologist or HAE specialist.

If patient currently receiving but never previously approved, review under Initial Therapy criteria.

Dosing

Dosing — Approve ONE of the following dosing regimens:

Dosing options: A. For patients ≥ 12 years: 300 mg per injection subcutaneously no more frequently than once every 2 weeks; OR B. For patients 6 to <12 years: 150 mg per injection subcutaneously no more frequently than once every 2 weeks; OR C. For patients <6 years: up to 150 mg per injection subcutaneously no more frequently than once every 4 weeks.

Approvals limited to these dosing regimens; doses outside may be considered case-by-case by clinician.

Concomitant long-term prophylactic therapy: Use of Takhzyro in combination with other HAE long-term prophylactic therapies is considered not medically necessary. Takhzyro has not been studied in combination with other prophylactic HAE therapies and combination long‑term prophylaxis is not recommended. Short‑term or on‑demand treatments for acute attacks (for example, C1 esterase inhibitor products) may be used as clinically appropriate.

Takhzyro is considered not medically necessary for any indication outside its FDA‑documented use as prophylaxis for hereditary angioedema due to C1‑INH deficiency. This includes, but is not limited to, use in combination with other long‑term HAE prophylactic agents or for diagnoses that do not meet the policy’s C1‑INH deficiency criteria.

Coding and Laboratory Thresholds

Covered HCPCS CodesHCPCSCovered

J0593

Injection, lanadelumab-flyo, 1 mg (Code may be used for Medicare when drug administered under direct supervision of a physician, not for use when drug is self-administered)

Functional C1-INH — laboratory threshold used for diagnosis/coverage (< 50% of normal)

Laboratory thresholdFunctional C1-INH < 50% of normal (baseline) per laboratory reference values

Documentation requirementBaseline laboratory documentation of functional C1-INH level required for initial therapy approvals

Role in diagnosisUsed as part of diagnostic criteria for HAE type I/II when combined with low serum C4

Provider Actions, Authorization, and Documentation

Prior Authorization

Prior Authorization Required — Prior authorization is required for Takhzyro

Prior authorization is required for Takhzyro; approve for up to 1 year when the patient meets initial or continuation therapy criteria and documentation requirements.

Prior authorization required for benefit coverage of Takhzyro; approvals issued for up to 1 year when criteria are met.
Prescriber requirement: Takhzyro must be prescribed by or in consultation with an allergist/immunologist or a physician who specializes in the treatment of HAE or related disorders.

Step Therapy

Step Therapy / Specialist Requirement — No step therapy specified; specialist prescribing or consultation required

No step therapy is specified. Because of the specialized skills required for evaluation and diagnosis and monitoring, approval requires Takhzyro to be prescribed by or in consultation with a specialist.

No step therapy specified.
Specialist prescribing or consultation required (allergist/immunologist or physician who specializes in HAE).

Documentation Required

Required Documentation — Documentation (e.g., chart notes, laboratory records) required for diagnostic criteria such as baseline functional C1-INH <50% and other supporting records

Documentation is required where noted in the criteria. Documentation may include, but is not limited to, chart notes, laboratory records, and prescription claims records. All documentation must include patient-specific identifying information.

Baseline functional C1-INH < 50% of normal at baseline [documentation required]; include laboratory reference values.
Baseline serum C4 lower than normal at baseline [documentation required]; include laboratory reference values.
Diagnosis of HAE type I or type II must be documented [documentation required].
If patient is currently receiving Takhzyro and previously met initial therapy criteria via the Coverage Review Department, continuation requires documentation of current therapy and a prescriber statement of favorable clinical response (e.g., decreased attack frequency, severity, or duration).

Denial Risk

Coding/Claims Denial Risk — Claims submitted without covered diagnosis or procedure codes listed in the policy will be denied as not covered; services billed with no appropriate codes at submission risk denial

Claims submitted without covered diagnosis or procedure codes listed in the policy will be denied as not covered. Services billed with no appropriate codes at submission risk denial.

Use appropriate codes when billing; claims lacking covered codes under this policy will be denied as not covered.
Considered medically necessary code listed in policy: J0593 (Injection, lanadelumab-flyo, 1 mg) — verify code applicability and payer guidance at time of service; code list may not be all-inclusive.

Definitions Related to HAE

HAE type I/II — diagnostic definition (functional C1-INH <50% and low serum C4 at baseline)

DefinitionHereditary angioedema (HAE) type I or II: diagnosis supported by low functional C1-INH (< 50% of normal) AND low serum C4 at baseline

Testing recommendedMeasure serum C4, C1-INH antigenic level, and C1-INH functional level when HAE is suspected

Guideline contextLow C4 plus low C1-INH antigenic or functional level is consistent with a diagnosis of HAE types I/II per HAE Association guidance

HAE with normal C1-INH (HAE-nC1INH / type III) — this diagnosis does NOT satisfy coverage under the C1-INH deficiency indication

Coverage exclusionHAE with normal C1-INH (HAE-nC1INH / type III) does NOT satisfy the policy requirement for coverage under the C1-INH deficiency indication

Clinical trial evidenceA Phase III trial of Takhzyro in HAE with normal C1-INH failed to show a significant reduction in attack number

Diagnostic distinctionHAE-nC1INH is characterized by normal C1-INH levels/function and should not be used to meet C1-INH deficiency criteria

Background

Takhzyro (lanadelumab‑flyo) is a human monoclonal antibody that targets and inhibits plasma kallikrein and is FDA‑indicated for prevention of hereditary angioedema (HAE) attacks in patients aged ≥ 2 years. The policy covers Takhzyro for long‑term prophylaxis of HAE due to C1‑INH deficiency (types I/II) when diagnostic criteria are documented — specifically baseline low serum C4 and functional C1‑INH < 50% of normal — or for patients currently receiving Takhzyro with documented clinical benefit. Prior authorization is required and approvals are issued for up to 1 year when coverage criteria and dosing limits are met.