ModifiedCentenePolicy CP.PHAR.213

Clinical Policy: Lumacaftor/Ivacaftor (Orkambi)

Medical necessity policy governing coverage criteria, dosing, and continuation requirements for Orkambi (lumacaftor/ivacaftor) for members with cystic fibrosis, applicable to Centene lines of business including Commercial, HIM, and Medicaid.

Policy Summary

PayerCentene

PolicyLumacaftor/Ivacaftor (Orkambi) clinical coverage criteria

Policy CodePolicy CP.PHAR.213

Change TypeMaterial revisions and additions

Effective DateMay 1, 2016

Next Review DateN/A

Key ActionSubmit prior authorization with documentation (diagnosis, CFTR genotype confirmation, baseline ppFEV1 when applicable) demonstrating member meets all approval criteria.

SourceLink

POLICY UPDATE CHANGES

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

Updated FDA approved indication and pediatric dosing to include ages 1 through <2 years and added new oral granule packet strengths.

Clarified continued therapy response criteria to specify improvement (e.g., decrease) in LCI from baseline and increase in ppFEV1 from baseline; later LCI removed.

Added Alyftrek to the list of CFTR modulators that must not be co-prescribed with Orkambi.

6 monthsinitial approval duration

≥1 yrminimum FDA-approved age

homozygous F508delrequired genotype

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Alyftrek addedAlyftrek concurrent exclusion

LCI removedLCI removed

Coverage Criteria

Initial Therapy — Covered when ALL of the following are met

Covered when ALL of the following are met:

Initial Approval: Diagnosis of cystic fibrosis confirmed by clinical symptoms in at least one organ system or positive newborn screen/genetic testing; evidence of CFTR dysfunction by genetic testing confirming two disease-causing CFTR mutations (one from each parental allele) and confirmation that the member is homozygous for the F508del mutation; prescribed by or in consultation with a pulmonologist; member meets the minimum FDA‑approved age for therapy (age ≥ 1 year per product labeling); for age ≥ 6 years: documentation of baseline percent predicted FEV1 (ppFEV1) performed within the last 90 days; dosing does not exceed the age‑ and weight‑based maximums specified in dosing guidance (see Dosage and Administration); Orkambi is not prescribed concurrently with other CFTR modulators (e.g., Kalydeco, Symdeko, Trikafta, Alyftrek).

Approval duration: 6 months

Continuation Therapy — Covered when ALL of the following are met (continuation requires a positive response or continuity provision)

Covered when ALL of the following are met (continuation requires a positive response or continuity provision):

Continued Therapy: Member currently receiving medication via the Centene benefit or previously met initial approval criteria OR member currently receiving medication and enrolled in a state/product with continuity of care regulations; member is responding positively to therapy: for age < 6 years — clinical improvement (e.g., decreased pulmonary exacerbations, increased BMI, improved respiratory symptoms); for age ≥ 6 years — stabilization or improvement (increase) in ppFEV1 from baseline; Orkambi is not prescribed concurrently with other CFTR modulators (e.g., Kalydeco, Symdeko, Trikafta, Alyftrek); requests for dose increases must not exceed the age‑ and weight‑based maximums in the dosing guidance.

Requests for use of lumacaftor/ivacaftor (Orkambi) for non‑FDA approved indications that are not specifically addressed in this policy will be excluded from coverage unless the provider submits sufficient clinical documentation demonstrating efficacy and safety in accordance with the Health Plan 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 applicable evidence of coverage documents.

Orkambi must not be prescribed concurrently with certain CFTR modulators. The policy was updated to explicitly add Alyftrek to the list of CFTR modulators that are excluded from concurrent use with lumacaftor/ivacaftor; concurrent prescribing with these agents will trigger a denial per the policy.

Use of lumacaftor/ivacaftor for indications that are not FDA‑approved and for which the provider does not provide acceptable off‑label documentation as described in the Health Plan off‑label policies will be considered not authorized/denied.

The policy no longer uses the Lung Clearance Index (LCI) as a criterion for coverage determinations. LCI was removed from the criteria to align with competitor analysis and standard of care.

Coding and Product Availability

NDCNDC

64764228301	Orkambi tablet lumacaftor 200 mg/ivacaftor 125 mg
64764228201	Orkambi tablet lumacaftor 100 mg/ivacaftor 125 mg
64764228401	Orkambi granule packet lumacaftor 75 mg/ivacaftor 94 mg
64764228501	Orkambi granule packet lumacaftor 100 mg/ivacaftor 125 mg
64764228601	Orkambi granule packet lumacaftor 150 mg/ivacaftor 188 mg

Minimum Age

Minimum age for FDA indication6 years

Approval Duration

Initial approval duration6 months

Provider Actions and Requirements

Prior Authorization

Prior Authorization and Dosing Limits

Prior authorization is required for lumacaftor/ivacaftor (Orkambi). Dosing must not exceed the age- and weight-based maximums specified in the policy. Approval duration is 6 months for initial and continued therapy authorizations.

Approval duration: 6 months
Dosing must not exceed age- and weight-based maximums as detailed in the Dosage and Administration section
Prior authorization required

Denial Risk

Concurrent CFTR Modulator Exclusion

Orkambi must not be prescribed concurrently with other CFTR modulators. Requests for concurrent use with CFTR modulators such as Kalydeco (ivacaftor), Symdeko (tezacaftor/ivacaftor), Trikafta (elexacaftor/tezacaftor/ivacaftor), or Alyftrek will be denied.

Concurrent CFTR modulator exclusion: Kalydeco, Symdeko, Trikafta, Alyftrek

Background

Orkambi is a combination of lumacaftor (a CFTR corrector) and ivacaftor (a CFTR potentiator) indicated to treat cystic fibrosis in patients who are homozygous for the F508del CFTR mutation. The product is FDA‑approved for use in patients aged ≥ 1 year, and dosing varies by age and weight with tablet and oral granule formulations; prior authorization and required documentation (including genotype confirmation and baseline pulmonary function where applicable) are described elsewhere in the policy.

Definitions

inv-21: percent predicted forced expiratory volume in 1 second (ppFEV1)

DefinitionPercent predicted forced expiratory volume in 1 second (ppFEV1)

Baseline requirement (age ≥6 years)Documentation of baseline ppFEV1 performed within the last 90 days is required for initial approval

Use for continued therapy (age ≥6 years)Continued therapy requires stabilization or improvement (increase) in ppFEV1 from baseline

inv-09: cystic fibrosis transmembrane conductance regulator (CFTR)

DefinitionCFTR = cystic fibrosis transmembrane conductance regulator

Genotype requirementFDA indication requires confirmation of CFTR dysfunction with two disease‑causing CFTR mutations and homozygous F508del for Orkambi

Policy Summary

PayerCentene

PolicyLumacaftor/Ivacaftor (Orkambi) clinical coverage criteria

Policy CodePolicy CP.PHAR.213

Change TypeMaterial revisions and additions

Effective DateMay 1, 2016

Next Review DateN/A

Key ActionSubmit prior authorization with documentation (diagnosis, CFTR genotype confirmation, baseline ppFEV1 when applicable) demonstrating member meets all approval criteria.

SourceLink

On This Page

Concurrent prescriptions will trigger denial of the Orkambi request

Note

Formulary / Non‑Formulary Routing

If the requested use is not listed under allowed diagnoses/indications, route the request per formulary/non‑formulary and off‑label policies for the applicable line of business.

For drugs on the formulary/PDL, see no coverage criteria policies: CP.CPA.190 (Commercial), HIM.PA.33 (Health Insurance Marketplace), CP.PMN.255 (Medicaid)
For drugs NOT on the formulary/PDL, see non‑formulary policies: CP.CPA.190 (Commercial), HIM.PA.103 (Health Insurance Marketplace), CP.PMN.16 (Medicaid)
For off‑label uses not addressed in this policy, refer to off‑label use policies: CP.CPA.09 (Commercial), HIM.PA.154 (Health Insurance Marketplace), CP.PMN.53 (Medicaid)

Documentation Required

Required Documentation and Administrative Requirements

Providers must submit documentation supporting that the member meets all approval criteria. Follow Health Plan-level administrative policies and applicable contract, coverage, state and federal requirements when providing documentation.

Required documentation: office chart notes, lab results, spirometry reports, genetic testing results, and other relevant clinical information
Providers are expected to exercise professional medical judgment and comply with applicable Health Plan administrative policies and legal/regulatory requirements
Coverage decisions are subject to all terms, conditions, exclusions, and limitations of the member's contract and evidence of coverage

Documentation Required

Baseline Pulmonary Function

For members age ≥6 years, submit baseline percent predicted FEV1 (ppFEV1) performed within the last 90 days. Appendix D notes that most children can perform spirometry by age 6; if spirometry is not possible, document inability and alternative assessments.

Baseline ppFEV1 required within 90 days for age ≥6 years
If spirometry cannot be performed (e.g., young children), document reason and any alternative clinical assessments per Appendix D

Denial Risk

Off‑Label Use, Step Therapy, and Denial Risk

Requests for uses not specifically listed in this policy or for non‑FDA indications will be denied unless sufficient documentation is provided per the applicable off‑label policies. The policy does not specify step therapy sequences; clinical judgment and referenced competitor/standard‑of‑care alignment guide therapy choices.

Off‑label use denial risk: non‑FDA indications not addressed here require off‑label policy evidence to be considered
Step therapy: not specified in this policy; refer to standard of care and formulary management practices

Denial Risk

Documentation to Support Medical Necessity and Contractual Denial Risk

Providers must follow Health Plan-level administrative policies and procedures and comply with contract terms when seeking coverage. Coverage decisions may be limited by the member's contract, state/federal law, and Health Plan policy changes.

Denial risk may arise from contract exclusions, coverage limitations, or failure to provide required documentation
The Health Plan may change, amend, or withdraw this clinical policy; applicable legal/regulatory requirements govern in case of discrepancy

Context in policyCFTR term listed in Appendix A (Abbreviation/Acronym Key) and used throughout dosing and criteria sections

inv-23: Lung Clearance Index (LCI) — Referenced as a previously included metric in criteria that was removed to align with standard of care and competitor analysis.

Metric removedLung Clearance Index (LCI) was removed from coverage criteria to align with competitor analysis and standard of care

Policy historyRemoval effective Date = 12.31.24; noted in P&T approval/3Q2025 updates

Appendix updateLCI supplemental information updated/removed from Appendix D and pediatric extension references

inv-24: Alyftrek — A CFTR modulator added to the list of therapies that are concurrently excluded with lumacaftor/ivacaftor per the policy updates.

Concurrent‑use exclusionAlyftrek added to the list of CFTR modulators that must not be co‑prescribed with lumacaftor/ivacaftor (Orkambi)

Other excluded CFTR modulatorsConcurrent prescription with Kalydeco, Symdeko, Trikafta (and now Alyftrek) will trigger denial

Policy update timingAlyftrek added during 3Q2025 annual review (references reviewed and updated)