CurrentCignaPolicy IP0432

Orkambi

Defines Cigna's prior authorization, medical necessity criteria, and coverage limitations for Orkambi for treatment of cystic fibrosis in patients homozygous for the F508del CFTR mutation; applies to Cigna-administered health benefit plans.

Policy Summary

PayerCigna

PolicyOrkambi

Policy CodePolicy IP0432

Change TypeRevised preferred product/age criteriadocumentation clarified

Effective DateSep 1, 2025

Next Review Date

Key ActionObtain prior authorization and submit required documentation (e.g., genotype showing two copies of F508del, chart notes, labs) for Orkambi approval.

SourceLink

POLICY UPDATE CHANGES

Preferred product criteria updated to require that for employer plans a patient ≥ 2 years must have tried and per prescriber experienced 'inadequate efficacy OR a significant intolerance' with Trikafta rather than the prior language.

Age threshold language changed from 'less than 6 years' to 'less than 2 years' in selected revisions.

Documentation requirement language added specifying what may be submitted when documentation is required.

≥ 1 yrMinimum FDA-approved age for Orkambi

1 yrTypical authorization length

TWO copiesRequired F508del mutations

Trikafta trial

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Coverage Criteria for Orkambi (lumacaftor/ivacaftor)

Initial Therapy (FDA-Approved Indication)

Covered when ALL of the following are met:

Orkambi - FDA-approved indication: Patient is ≥ 1 year of age (A); AND documentation is provided that the patient has TWO copies of the F508del mutation in the cystic fibrosis transmembrane conductance regulator gene (B); AND patient meets at least ONE of: positive cystic fibrosis newborn screening test, family history of cystic fibrosis, or clinical presentation consistent with signs and symptoms of cystic fibrosis (C); AND evidence of abnormal CFTR function demonstrated by at least ONE of: elevated sweat chloride test, two CF-causing CFTR mutations, or abnormal nasal potential difference (D); AND medication is prescribed by or in consultation with a pulmonologist or a physician who specializes in the treatment of cystic fibrosis (E); AND preferred product criteria is met (F).

Approval duration: 1 year when criteria met

Orkambi (lumacaftor/ivacaftor) is considered not medically necessary for uses outside its FDA‑approved indication for patients who are homozygous for the F508del CFTR mutation. Explicitly excluded indications include: patients who are heterozygous for the F508del mutation (only one copy of F508del), use in combination with other CFTR modulators that contain ivacaftor (for example, Kalydeco®, Symdeko®, Trikafta®, Alyftrek™), and treatment of infertility. The list is not all‑inclusive and will be updated as new published data become available.

Specifically, Orkambi is not indicated for patients with only one copy of the F508del mutation (heterozygous F508del). Combining Orkambi with other CFTR modulators that include ivacaftor is contraindicated as Orkambi already contains ivacaftor; examples of such modulators include Kalydeco®, Symdeko®, Trikafta®, and Alyftrek™. Use of Orkambi for management of infertility is also considered not medically necessary. A patient with a diagnosis of cystic fibrosis should be evaluated against the FDA‑approved indication criteria to determine eligibility for coverage.

Coding and Diagnostic Support

Covered/Referenced Codes (not explicitly listed)mixed

NDCs and specific billing codes

Not listed explicitly in the document; prescribing information referenced.

inv-05: Sweat chloride — diagnostic thresholds

Diagnostic threshold supporting CFSweat chloride ≥ 60 mmol/L establishes a CF diagnosis.

Intermediate/indeterminate rangeSweat chloride 30–59 mmol/L requires CFTR genetic analysis and possibly further physiologic testing (NPD or ICM) to determine diagnosis.

Threshold making CF unlikelySweat chloride < 30 mmol/L makes a CF diagnosis unlikely; rarely CF may be considered only if alternatives are excluded and other confirmatory tests support CF.

Provider Actions, Prior Authorization, and Documentation Requirements

Prior Authorization

Prior Authorization Required

Prior Authorization is required for benefit coverage of Orkambi. Approvals are typically provided for 1 year when criteria are met. Because of the specialized skills required for evaluation and diagnosis and monitoring, Orkambi must be prescribed by or in consultation with a physician who specializes in the treatment of cystic fibrosis.

Approvals typically valid for 1 year when criteria are met.
Prescriber requirement: must be prescribed by or in consultation with a pulmonologist or physician who specializes in cystic fibrosis.

Step Therapy

Preferred product / step requirement (Employer Plans)

Employer-specific step requirement: For Employer Plans on the Total Savings Drug List, Orkambi (lumacaftor/ivacaftor) requires that ONE of the following be met: the patient is ≥ 2 years AND, according to the prescriber, has tried Trikafta (tablets or oral granules) and experienced inadequate efficacy or significant intolerance; OR the patient is < 2 years of age; OR the patient has already been started on therapy with Orkambi. Trikafta trial or intolerance may itself require prior authorization per the prescriber's report.

Background

Orkambi combines a CFTR corrector (lumacaftor) with a CFTR potentiator (ivacaftor) and is indicated for treatment of cystic fibrosis in patients who are homozygous for the F508del mutation. The efficacy and safety of Orkambi have been established for this population and have not been established for other genotypes or when used in combination with other ivacaftor‑containing modulators. Treatment decisions should follow the FDA‑approved indication and the policy criteria for documentation and authorization.

Definitions

inv-11: Cystic fibrosis (CF) — diagnostic definition/key points

Core diagnostic definitionCystic fibrosis (CF) is diagnosed by clinical presentation plus evidence of CFTR dysfunction; Orkambi is indicated for patients ≥ 1 year who are homozygous for the F508del CFTR mutation.

Genotype requirement for OrkambiTwo copies (homozygous) of the F508del mutation on the CFTR gene; if genotype unknown, use an FDA‑cleared CF mutation test to detect F508del on both alleles.

Evidence of CFTR dysfunctionDemonstrated by elevated sweat chloride, identification of two CF‑causing CFTR mutations, or abnormal nasal potential difference (NPD) or intestinal current measurement (ICM).

When to perform additional testingFor intermediate sweat chloride (30–59 mmol/L) perform CFTR genetic analysis and, if genotype is undefined, consider full gene sequencing or physiologic testing; challenging cases should be evaluated at an accredited CF Foundation Care Center.