CurrentCignaPolicy N/A

Hereditary Angioedema - Orladeyo Prior Authorization Policy

Cigna coverage policy governing prior authorization, medical necessity, and continuation criteria for Orladeyo (berotralstat capsules and oral pellets) when used for prophylaxis of hereditary angioedema (HAE) in eligible patients.

Policy Summary

PayerCigna

PolicyHereditary Angioedema - Orladeyo Prior Authorization Policy

Policy CodePolicy N/A

Change TypeMaterial revisions (age eligibility expandednew formulation addedcontinuation criteria clarified)

Effective DateN/A

Next Review DateN/A

Key ActionObtain prior authorization and document C1‑INH functional level and serum C4 to support initiation or continuation of Orladeyo; prescriber must be or consult an allergist/immunologist or HAE specialist.

SourceLink

POLICY UPDATE CHANGES

Orladeyo oral pellets (new formulation) were added to the policy with the same requirements applied as the tablets.

Initial therapy age requirement changed from ≥ 12 years to ≥ 2 years of age.

Under 'Patient is currently receiving Orladeyo', the age requirement (≥12) was deleted.

Added that patients who previously met initial therapy criteria under the Coverage Review Department and are currently receiving Orladeyo only need to meet continuation criteria; if prior approval was from another entity, initial therapy criteria must be met.

≥2minimum age for initial Orladeyo therapy

1 yrstandard approval duration

Not coveredconcomitant long-term use

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Specialistprescriber requirement

Coverage Criteria for Orladeyo (berotralstat)

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

Covered when ONE of the following is met (A or B):

A: Initial therapy: Patient is ≥ 2 years of age AND patient has HAE type I or II confirmed by (a) low functional C1-INH protein (<50% of normal) [documentation required] AND (b) low serum C4 [documentation required] AND medication is prescribed by or in consultation with an allergist/immunologist or a physician who specializes in HAE or related disorders.age >= 2; C1-INH <50%; low C4

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

B: Currently receiving Orladeyo (continuation): Patient has a diagnosis of HAE type I or type II [documentation required] AND per prescriber the patient has had a favorable clinical response since initiating Orladeyo (decrease in attack frequency, severity, or duration) AND medication is prescribed by or in consultation with an allergist/immunologist or a physician who specializes in HAE or related disorders.clinical improvement as reported by prescriber

If prior approval was obtained from an entity other than the Coverage Review Department, the patient must meet Initial Therapy criteria.

Concomitant long-term use of Orladeyo (berotralstat capsules or oral pellets) with other hereditary angioedema (HAE) prophylactic therapies is considered not medically necessary. The policy notes that Orladeyo has not been studied in combination with other prophylactic agents and expressly does not recommend combination therapy for ongoing prophylaxis. Examples of other HAE prophylactic therapies include Cinryze, Haegarda, and Takhzyro.

Orladeyo is considered not medically necessary for any indications not specified in this policy. This includes use as part of combination long-term prophylactic regimens with other HAE prophylactic agents. The policy allows use of other medications, such as C1‑INH products, for on‑demand treatment of acute HAE attacks or for short‑term (procedural) prophylaxis, but not for chronic combined prophylaxis with Orladeyo.

Billing and Coding

Covered CPT Codesmixed

No codes listed

C1-INH functional level

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

DocumentationBaseline laboratory report demonstrating functional C1-INH level is required

Role in diagnosisLow functional C1-INH is one of two required biochemical criteria to confirm HAE type I or II

Serum C4 level

ThresholdSerum C4 level lower than normal at baseline as defined by laboratory reference values

DocumentationBaseline laboratory report demonstrating low serum C4 is required

Provider Actions, Prior Authorization, and Documentation

Prior Authorization

Prior Authorization Recommended

Prior authorization is recommended for Orladeyo; approval for the FDA‑approved HAE prophylaxis indication is granted for 1 year when initial or continuation criteria are met. Because of the specialized skills required for evaluation and diagnosis, Orladeyo must be prescribed by or in consultation with an allergist/immunologist or a physician who specializes in HAE or related disorders.

Prior authorization recommended
Approvals granted for up to 1 year
Prescriber requirement: allergist/immunologist or HAE specialist

Step Therapy

Step Therapy / Guideline Context

Guideline context supports consideration of long‑term prophylaxis based on disease activity, burden, control, and patient preference. First‑line long‑term prophylaxis options cited in guideline recommendations include plasma‑derived C1‑INH (IV or subcutaneous), Takhzyro (lanadelumab), and Orladeyo; androgens are not recommended first‑line. Specialist involvement is required by policy for prescribing and assessment.

Background

Orladeyo (berotralstat) is an oral plasma kallikrein inhibitor available as capsules and oral pellets and is labeled for prophylaxis of hereditary angioedema (HAE) attacks. It is not studied in combination with other long‑term prophylactic therapies and is not indicated for treatment of acute HAE attacks.

Definitions

HAE type I or II — Definition

DefinitionHereditary angioedema (HAE) type I or II due to C1‑INH deficiency is diagnosed by low functional C1‑INH (< 50% of normal) and low serum C4 levels per laboratory reference ranges

ExclusionHAE with normal C1‑INH (HAE type III) does NOT satisfy this diagnostic requirement

Supporting guidanceGuidelines recommend measurement of serum C4, C1‑INH antigenic level, and C1‑INH functional level when HAE is suspected

Policy Summary

PayerCigna

PolicyHereditary Angioedema - Orladeyo Prior Authorization Policy

Policy CodePolicy N/A

Change TypeMaterial revisions (age eligibility expandednew formulation addedcontinuation criteria clarified)

Effective DateN/A

Next Review DateN/A

SourceLink

On This Page

Role in diagnosisLow C4 plus low C1-INH antigenic or functional level is consistent with HAE types I/II

Assess long‑term prophylaxis at each visit per guidelines
First‑line options: plasma‑derived C1‑INH, Takhzyro, Orladeyo
Androgens not recommended first‑line
Specialist involvement required

Documentation Required

Documentation is required where noted in the criteria and must include patient‑specific identifying information. Acceptable documentation may include, but is not limited to, chart notes, laboratory records, and prescription claims records. Specific lab documentation required for initial therapy includes baseline functional C1‑INH level and baseline serum C4 level as defined by laboratory reference values; diagnosis documentation is required for patients currently receiving therapy.

Chart notes, laboratory records, prescription claims records may be requested
Baseline lab results required for Initial Therapy: functional C1‑INH and serum C4 [documentation required]
Diagnosis documentation required for patients currently receiving Orladeyo

Denial Risk

Billing and Coding Denial Risk

Claims submitted for services that are not accompanied by covered diagnosis and/or procedure codes under the applicable coverage policy will be denied as not covered. Providers must use the most appropriate codes as of the submission date; reimbursement is allowed only when claims are submitted in accordance with the policy.

Use covered diagnosis/procedure codes as specified by the policy
Claims without covered codes will be denied as not covered
Use the most appropriate codes effective on the date of submission

Denial Risk

Concomitant Prophylactic Therapy — Not Medically Necessary

Orladeyo is considered not medically necessary for concomitant long‑term use with other HAE prophylactic therapies (e.g., Cinryze, Haegarda, Takhzyro). Combination therapy for long‑term prophylaxis has not been studied and is not recommended; short‑term (procedural) prophylaxis or on‑demand treatment with other agents is permitted.

Concomitant long‑term use with other HAE prophylactic therapies is not medically necessary
Examples: Cinryze, Haegarda, Takhzyro
Other agents may be used for on‑demand treatment or short‑term procedural prophylaxis