ModifiedmhnPolicy CP.PHAR.213

Clinical Policy: Lumacaftor/Ivacaftor (Orkambi)

Medical necessity policy describing coverage criteria, dosing, and authorization requirements for Orkambi for members with cystic fibrosis who are homozygous for the F508del CFTR mutation. Affects prescribers, pharmacists, and reviewers managing commercial, HIM, and Medicaid lines of business.

Policy Summary

Payermhn

PolicyLumacaftor/Ivacaftor (Orkambi) for Cystic Fibrosis

Policy CodePolicy CP.PHAR.213

Change TypeCriteria updates and exclusions (material)

Effective DateMay 1, 2016

Next Review Date

Key ActionSubmit prior authorization with documentation of diagnosis, homozygous F508del genotype, baseline ppFEV1 (if ≥6 years), and evidence of clinical response for continued therapy.

SourceLink

POLICY UPDATE CHANGES

Added Alyftrek to list of CFTR modulator concurrent exclusion criteria.

For continued therapy clarified positive response as stabilization or improvement in ppFEV1 and removed lung clearance index from criteria.

Updated initial approval criteria to include pediatric ages 1 through <2 years per FDA pediatric extension and added new oral granule packet strength.

Removed lung clearance index from criteria to align with competitor analysis and standard of care.

For continued therapy, clarified positive response as an 'improvement' (e.g., decrease) of LCL and improvement of ppFEV1 as an 'increase from baseline'.

For initial therapy, removed criterion 'ppFEV1 that is between 40 - 90%' from documentation of member's ppFEV1 to align with other CFTR modulator criteria.

≥1 yrMinimum covered age

Homozygous F508del

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Coverage Criteria for Lumacaftor/Ivacaftor (Orkambi)

Initial Therapy Criteria

Covered when ALL of the following are met

Initial Approval - CF: 1. Diagnosis of cystic fibrosis confirmed by all of the following: (a) clinical symptoms consistent with CF OR positive newborn screen or genetic testing for siblings; (b) evidence of CFTR dysfunction confirmed by either elevated sweat chloride ≥ 60 mmol/L OR genetic testing confirming two disease‑causing CFTR mutations (one from each parental allele); (c) confirmation that member is homozygous for the F508del mutation in the CFTR gene.

Age and prescriber: 2. Age ≥ 1 year.

3. Medication prescribed by or in consultation with a pulmonologist.

Baseline measures: For members age ≥ 6 years: documentation of baseline percent predicted FEV1 (ppFEV1) performed within the last 90 days.ppFEV1 baseline within 90 days

Approval duration: 6 months

Concurrent therapy exclusion: Orkambi (lumacaftor/ivacaftor) is not prescribed concurrently with other CFTR modulators (examples include Alyftrek, Kalydeco, Symdeko, Trikafta).

Concurrent use with Alyftrek added to exclusions

Dosing limits: Dose requested does not exceed the age- and weight-based maximum dosing bands as specified in the dosing table (age/weight dosing for 1–<2 years, 2–5 years, 6–11 years, and ≥12 years).

See dosing table for exact mg and packet/tablet regimens

Documentation required: Provider must submit supporting documentation (office notes, lab results or other clinical information) demonstrating members meet all criteria, including diagnostic confirmation and genotype (homozygous F508del).

Insufficient documentation may result in denial

Continuation Therapy Criteria

Covered when ALL of the following are met

Continued Therapy - CF: 1. Member is currently receiving medication via the plan benefit and previously met initial approval criteria OR is receiving medication and is covered under applicable continuity-of-care provisions.

Clinical response documentation: 2. For age < 6 years: documentation of positive clinical response (examples: decreased pulmonary exacerbations, increased BMI, improvement in respiratory symptoms). For age ≥ 6 years: documentation of a positive response evidenced by stabilization or improvement (increase) in percent predicted FEV1 (ppFEV1) from baseline.stabilization or increase in ppFEV1 for ≥6 yrs

Lung Clearance Index (LCI) is no longer required for continued therapy assessment

Concurrent therapy exclusion: 3. Orkambi is not prescribed concurrently with other CFTR modulators (e.g., Alyftrek, Kalydeco, Symdeko, Trikafta).

Alyftrek added to concurrent exclusion list

Updated Coverage Criteria

Criteria updates and clarifications

Initial Therapy Criteria (updated): Requirement for a ppFEV1 between 40–90% has been removed from initial therapy documentation to align with other CFTR modulator criteria.ppFEV1 40-90% removed

See full policy for remaining initial therapy criteria

Continued Therapy Criteria (clarified): For continued therapy, positive response should be documented as an improvement: historically LCI decrease and an increase in ppFEV1 from baseline. LCI has been removed from required measures; continued therapy evaluation aligns to ppFEV1 and clinical measures.improvement vs baseline

LCI removed from required criteria; use ppFEV1 and clinical endpoints

Concurrent Therapy Exclusions (added): Concurrent use of Alyftrek has been added to the list of excluded CFTR modulators; other CFTR modulators remain excluded per policy.

This policy addresses coverage for lumacaftor/ivacaftor (Orkambi) for the FDA‑approved indication of cystic fibrosis in patients who meet the specific criteria below. Non‑FDA approved indications that are not addressed in this policy are not authorized unless the provider submits sufficient documentation of efficacy and safety consistent with the applicable off‑label use policies (see CP.CPA.09 for commercial, HIM.PA.154 for Health Insurance Marketplace, and CP.PMN.53 for Medicaid) or other evidence of coverage provisions.

Orkambi (lumacaftor/ivacaftor) must not be prescribed concurrently with Alyftrek. Alyftrek has been added to the list of excluded CFTR modulators and concurrent use is prohibited per this policy; requests indicating concomitant use with Alyftrek will not meet coverage criteria.

Coverage under this policy is limited to members who meet the documented eligibility requirements. Specifically, Orkambi is not covered for patients who are not homozygous for the F508del CFTR mutation, and concurrent use with other CFTR modulators (for example, Kalydeco, Symdeko, Trikafta, and Alyftrek) is prohibited.

Coverage determinations are made in the context of the member's benefit plan. This policy is subject to the terms, conditions, exclusions, and limitations of the member's contract of insurance and any applicable state or federal requirements. For Medicaid members, state‑specific provisions and addenda govern coverage where they conflict with this policy.

Coding

Coding — none specifiedmixed

N/A	No specific CPT/HCPCS/ICD-10 procedure or diagnosis codes listed in this document.

Affected Codesmixed

affected codes	Placeholder from document indicating affected codes for prior authorization
lumacaftor 100 mg / ivacaftor 125 mg	Tablets: lumacaftor 100 mg and ivacaftor 125 mg (product availability)
lumacaftor 200 mg / ivacaftor 125 mg	Tablets: lumacaftor 200 mg and ivacaftor 125 mg (product availability)
lumacaftor 75 mg / ivacaftor 94 mg	Oral granule packet: lumacaftor 75 mg and ivacaftor 94 mg (product availability)
lumacaftor 100 mg / ivacaftor 125 mg (packet)	Oral granule packet: lumacaftor 100 mg and ivacaftor 125 mg (product availability)
lumacaftor 150 mg / ivacaftor 188 mg	Oral granule packet: lumacaftor 150 mg and ivacaftor 188 mg (product availability)

Sweat chloride

Diagnostic sweat chloride threshold≥ 60 mmol/L

Use in diagnosisUsed as evidence of CFTR dysfunction when clinical features are present or with genetic testing

Alternative confirmationGenetic testing confirming two disease‑causing CFTR mutations is an alternative to elevated sweat chloride

ppFEV1 range (removed)

Previously required ppFEV1 range (removed)40 - 90%

Reason for removalRemoved to align initial therapy documentation with other CFTR modulator criteria

Provider Actions and Authorization Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required for Orkambi (lumacaftor/ivacaftor). Initial approvals are granted for 6 months. Requests must be submitted to the health plan and are subject to the member's benefit coverage and applicable state/federal requirements.

Approval duration: 6 months
Prior authorization required

Documentation Required

Required Supporting Documentation / Denial Risk

Providers must submit documentation (office chart notes, labs, genetic testing, imaging, or other clinical information) supporting that the member meets all approval criteria. Incomplete or missing documentation (diagnosis confirmation, genotype, age, baseline measures, prescribing clinician specialty) may result in denial.

Required supporting documentation: office chart notes, lab results, genetic testing, and other clinical information
Denial risk if documentation (diagnosis, genotype, age, baseline measures, prescribing clinician information) is missing

Background

Orkambi is a combination cystic fibrosis transmembrane conductance regulator (CFTR) modulator containing lumacaftor and ivacaftor. Lumacaftor acts as a corrector that improves the conformational stability of F508del‑CFTR, while ivacaftor acts as a potentiator that increases channel gating. The medication is FDA‑approved for treatment of cystic fibrosis in patients aged ≥1 year who are homozygous for the F508del mutation. Diagnostic confirmation requires clinical features of CF plus evidence of CFTR dysfunction (for example, elevated sweat chloride ≥60 mmol/L or genetic testing demonstrating two disease‑causing mutations).

Definitions and Abbreviations

ppFEV1 definition

DefinitionPercent predicted forced expiratory volume in 1 second (ppFEV1)

UseUsed to document baseline pulmonary function and response to therapy

Typical testing ageMost children can perform spirometry by age 6; some younger children may be able to perform the test

CFTR

AbbreviationCFTR

Full termCystic fibrosis transmembrane conductance regulator

ContextListed in Appendix A: abbreviation/acronym key

Revision History and Policy Changes

2025-04-14concurrent_exclusion_addedLatest

Added Alyftrek to the list of excluded concurrent CFTR modulators for lumacaftor/ivacaftor.

2024-12-31measure_removed

Removed lung clearance index (LCI) from required continuation/response criteria to align with standard of care.

2024-05-09initial_criteria_revised

Policy Summary

Payermhn

PolicyLumacaftor/Ivacaftor (Orkambi) for Cystic Fibrosis

Policy CodePolicy CP.PHAR.213

Change TypeCriteria updates and exclusions (material)

Effective DateMay 1, 2016

Next Review Date

Key ActionSubmit prior authorization with documentation of diagnosis, homozygous F508del genotype, baseline ppFEV1 (if ≥6 years), and evidence of clinical response for continued therapy.

SourceLink

On This Page

Documentation Required

Documentation of Treatment Response

For continuation of therapy, providers should document clinical response. Response should be demonstrated as improvement in pulmonary function (increase in ppFEV1 from baseline). Lung clearance index (LCI) has been removed from required measures and should not be relied on as a mandatory documentation metric.

Continued therapy: document increase in ppFEV1 from baseline
LCI removed from required measures

Note

Refer to Formulary / Off‑Label Policies When Applicable

If the requested use is not listed in this policy (diagnosis, age, dosing) or the drug label has changed within the last 6 months, refer to the applicable formulary or off‑label policies for the member's line of business before approving: formulary/non‑formulary policies (CP.CPA.190, HIM.PA.33, CP.PMN.255, HIM.PA.103, CP.PMN.16) or off‑label use policies (CP.CPA.09, HIM.PA.154, CP.PMN.53).

Refer to formulary/no coverage or non‑formulary policies for recent label changes
Refer to off‑label use policies when requested use is not listed in this policy
Commercial, marketplace, and Medicaid policy references: CP.CPA.190, HIM.PA.33, CP.PMN.255, HIM.PA.103, CP.PMN.16, CP.CPA.09, HIM.PA.154, CP.PMN.53

Denial Risk

Insufficient Documentation or Non‑Approved Indication

Insufficient documentation or requests for non‑approved indications may be denied. Ensure the submission includes confirmed CF diagnosis, documentation of CFTR dysfunction (elevated sweat chloride or two disease‑causing CFTR mutations), confirmation of homozygous F508del genotype (when required), member age, prescribing clinician specialty (pulmonologist or consultation), baseline ppFEV1 (where applicable), and dosing information consistent with policy limits.

Denial risk for insufficient documentation or non‑approved indication
Required elements: confirmed CF diagnosis, evidence of CFTR dysfunction, homozygous F508del confirmation, age, prescribing clinician specialty, baseline ppFEV1 (if ≥ 6 years), dosing consistent with policy