CurrentCignaPolicy IP0096

Berotralstat (Orladeyo) for hereditary angioedema prophylaxis

Defines medical necessity, reauthorization, authorization duration, and exclusions for berotralstat (Orladeyo) capsules used as prophylaxis to prevent hereditary angioedema (HAE) attacks in patients aged 12 and older for Cigna-administered benefit plans.

Policy Summary

PayerCigna

PolicyBerotralstat (Orladeyo) for hereditary angioedema prophylaxis

Policy CodePolicy IP0096

Change TypeAnnual Revision (no criteria changes)

Effective Date

Next Review Date

Key ActionObtain medical necessity review and required documentation (diagnosis, genetic or lab confirmation, and prescribing by or consultation with an allergist/immunologist) for Cigna-administered plans.

POLICY UPDATE CHANGES

Annual Revision, Summary of Changes = No criteria changes.

1Covered Indication (HAE prophylaxis)

3Reauthorization criteria items

1Excluded use: concomitant prophylactic therapy

Coverage Summary

Coverage stance: covered_with_criteria for berotralstat (Orladeyo) capsules for prophylaxis to prevent hereditary angioedema (HAE) attacks in patients aged >= 12 years. Policy identifier: IP0096. Effective/last review date: 2025-01-01. Scope summary: Defines medical necessity, reauthorization, authorization duration, and exclusions for berotralstat (Orladeyo) capsules used as prophylaxis to prevent hereditary angioedema (HAE) attacks in patients aged 12 and older for Cigna-administered benefit plans.

Initial Therapy / Medically Necessary Criteria

Numeric / Laboratory Thresholds

Age>= 12 years

C1-INH functional level< 50% of normal (baseline), as documented by laboratory reference values

C1-INH antigenic level< 50% of normal (baseline), as documented by laboratory reference values

C4 levelBelow the lower limit of normal as defined by the laboratory performing the test

Reauthorization / Continuation Therapy Criteria

Reauthorization / Continuation Therapy

Continuation of berotralstat (Orladeyo) is considered medically necessary for hereditary angioedema prophylaxis when ALL of the following are met:

ALL of the following

The initial medical necessity criteria have been met prior to the start of Orladeyo therapy
There is documentation of beneficial response since initiating Orladeyo prophylactic therapy compared with baseline (e.g., decrease in HAE acute attack frequency, decrease in HAE attack severity, or decrease in duration of HAE attacks)
Examples provided are illustrative, not exclusive
Medication continues to be prescribed by, or in consultation with, an allergist/immunologist

Initial approval duration and reauthorization approval duration are each up to 12 months.

Not Medically Necessary / Experimental or Unproven Uses

Any other use is considered experimental, investigational or unproven, including the following (this list may not be all inclusive):

ANY of the following

Concomitant use with other Hereditary Angioedema (HAE) prophylactic therapies (examples: Cinryze, Haegarda, Takhzyro). Orladeyo 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

Provider Actions & Prior Authorization

Prior Authorization

Prior authorization required

Coverage policy applies to Cigna-administered plans and medical necessity review is required; documentation must confirm diagnosis and meet listed laboratory/genetic criteria and that medication is prescribed by or in consultation with an allergist/immunologist.

Documentation Required

Documentation of diagnostic testing

Provide genetic testing showing a monoallelic pathogenic variant in SERPING1, F12, ANGPT1, PLG, or KNG1 OR a C4 below the laboratory lower limit of normal plus low C1‑INH functional or antigenic level (<50% of normal) as documented by laboratory reference values.

Documentation Required

Document clinical benefit for reauthorization

For reauthorization, document beneficial response since initiating Orladeyo compared with baseline (examples: decreased HAE acute attack frequency, decreased attack severity, or decreased attack duration) and that the medication continues to be prescribed by, or in consultation with, an allergist/immunologist.

Billing Rule

Initial and reauthorization durations

Initial approval duration: up to 12 months. Reauthorization approval duration: up to 12 months.

Background

Background: Orladeyo (berotralstat) is an oral plasma kallikrein inhibitor indicated for prophylaxis to prevent HAE attacks in patients aged >= 12 years. Guidelines recommend assessing for long-term prophylaxis at visits based on disease activity, burden, control, and patient preference; treatment decisions should reflect individual needs. WAO/EAACI (2021) includes Orladeyo as a supported first-line option for long-term prophylaxis.