ModifiedmhnPolicy CP.PHAR.377

Tezacaftor/ivacaftor (Symdeko) for cystic fibrosis

Defines medical necessity criteria, documentation, dosing limits, and continuity requirements for coverage of tezacaftor/ivacaftor (Symdeko) for members with cystic fibrosis aged ≥6 years within the payer's lines of business.

Policy Summary

Payermhn

PolicyTezacaftor/ivacaftor (Symdeko) for cystic fibrosis

Policy CodePolicy CP.PHAR.377

Change TypeCriteria revisions and dosing updates

Effective DateApr 3, 2018

Next Review Date

Key ActionSubmit prior authorization with documentation of CF diagnosis, baseline ppFEV1 within 90 days, genotype or sweat chloride, and absence of concurrent excluded CFTR modulators.

SourceLink

POLICY UPDATE CHANGES

For initial approval criteria, removed requirement 'chart notes showing ppFEV1 that is between 40 - 90%' and revised to 'documentation of member's baseline percent predicted forced expiratory volume in 1 second (ppFEV1)'.

For continued therapy, revised criteria from specific stratified stabilization/increase language to 'stabilization or improvement (e.g., increase) in ppFEV1 from baseline'.

Updated dosing criteria to include maximum dosing stratified by age and weight.

Added Alyftrek to list of CFTR modulator concurrent exclusion criteria.

≥6Minimum age for coverage

12 moAuthorization length

ppFEV1 ≤90dBaseline lung function

Not allowed

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Concurrent modulator exclusion

Coverage Criteria for Tezacaftor/Ivacaftor (Symdeko)

Initial Approval Criteria - Cystic Fibrosis

Covered when ALL of the following are met:

ALL of the following

Diagnosis confirmation: Diagnosis of cystic fibrosis confirmed by all of the following: (a) clinical symptoms consistent with CF in ≥1 organ system, or positive newborn screen or genetic testing for siblings of patients with CF; (b) evidence of CFTR dysfunction by one of: elevated sweat chloride ≥60 mmol/L or genetic testing confirming two disease-causing CFTR mutations (one from each parental allele); (c) either homozygous F508del or presence of at least one CFTR mutation responsive to Symdeko based on in vitro data/clinical evidence (see Appendix D/E)
See Appendix D/E for mutation lists
Patient factors: Age ≥ 6 years; prescribed by or in consultation with a pulmonologist; documentation of member's baseline percent predicted FEV1 (ppFEV1) performed within the last 90 daysage >=6
Baseline ppFEV1 required within 90 days
Therapy constraints and dosing: Symdeko is not prescribed concurrently with other CFTR modulators (e.g., Alyftrek, Kalydeco, Orkambi, Trikafta); dose does not exceed age/weight-specific limits: for ages 6 to <12 years and <30 kg — tezacaftor 50 mg/ivacaftor 150 mg per day (one tezacaftor/ivacaftor tablet in morning + ivacaftor tablet in evening); for ages ≥12 years or ages 6 to <12 years weighing ≥30 kg — tezacaftor 100 mg/ivacaftor 300 mg per day (one tezacaftor/ivacaftor tablet in morning + ivacaftor tablet in evening).dose limits per age/weight
Reduce dose for moderate/severe hepatic impairment and with moderate/strong CYP3A inhibitors

Continued Therapy - Cystic Fibrosis

Continued coverage when ALL of the following are met:

ALL of the following

Eligibility for continuation: Member meets one of the following: currently receiving medication via Centene benefit or previously met initial approval criteria; OR member is receiving medication and is enrolled in a state/product with continuity of care regulations (state addendums apply)
Response to therapy: Member is responding positively to therapy as evidenced by stabilization or improvement (e.g., increase) in ppFEV1 from baseline
Ongoing therapy constraints: Symdeko is not prescribed concurrently with other CFTR modulators (e.g., Alyftrek, Kalydeco, Orkambi, Trikafta); if request is for a dose increase, new dose must not exceed age/weight-specific maximums (same limits as initial approval)
Approval duration: 12 months

Initial and Continued Therapy (summary)

Covered when criteria for genetic responsiveness and documentation are met and dosing is according to age/weight

Genetic confirmation: Documentation of two disease-causing CFTR mutations (one from each parental allele) OR documentation that the member has CFTR mutations listed as responsive to Symdeko in the appendices

Refer to CFF Mutation Analysis Program (MAP) for testing

Baseline lung function: Documentation of member's baseline percent predicted FEV1 (ppFEV1) performed within the last 90 days (policy revised to require baseline ppFEV1 and removed prior 40–90% range)

Baseline ppFEV1 used to assess stabilization or improvement for continued therapy

Dosing eligibility and safety: Dosing must follow stratified age/weight regimens: ages 6–<12 years <30 kg vs ≥30 kg, or age ≥12 years as specified; maximum daily doses as listed in dosing table; reduce dose for moderate/severe hepatic impairment and when co-administered with moderate/strong CYP3A inhibitors

Maximum daily doses: 6–<12 y & <30 kg: tezacaftor 50 mg/ivacaftor 150 mg per day; ≥12 y or 6–<12 y & ≥30 kg: tezacaftor 100 mg/ivacaftor 300 mg per day

Non–FDA approved indications for tezacaftor/ivacaftor (Symdeko) that are not specifically addressed in this policy are not authorized unless the provider submits adequate supporting documentation consistent with the payer's off‑label use policies. Refer to the applicable off‑label coverage policies (for example, CP.CPA.09 for commercial lines of business, HIM.PA.154 for the health insurance marketplace, or CP.PMN.53 for Medicaid) or other evidence of coverage documentation when requesting authorization for non‑FDA indications.

Symdeko must not be prescribed concurrently with other CFTR modulators that are listed as excluded by this policy. The concurrent‑use exclusion list was updated to include Alyftrek; requests that indicate concomitant use with Alyftrek or other excluded CFTR modulators may be denied.

Policy revisions during routine reviews consolidated and clarified prior approval requirements and durations. Notably, initial approval criteria were revised to require documentation of the member’s baseline percent predicted FEV1 (ppFEV1) rather than specifying a 40–90% ppFEV1 range, and continued therapy language was updated to a more general requirement for stabilization or improvement (e.g., increase) in ppFEV1 from baseline. Legacy initial approval duration language was also reviewed and aligned with current plan templates and approval timelines.

Coding and Product Information

Drug codesmixed

NDC	Not listed in this part of the document

Product availability (NDC)NDC

NDC(s) not listed

Product availability: co-packaged tezacaftor 50 mg/ivacaftor 75 mg fixed-dose combination tablets with ivacaftor 75 mg tablets OR tezacaftor 100 mg/ivacaftor 150 mg fixed-dose combination tablets with ivacaftor 150 mg tablets

inv-09: Sweat chloride

Sweat chloride threshold≥ 60 mmol/L

Acceptable evidenceElevated sweat chloride meeting threshold or genetic testing confirming two disease-causing CFTR mutations (one from each parental allele)

Reference location in policyInitial approval criteria I.A.1.b.i

inv-10: Baseline ppFEV1 timing

Baseline ppFEV1 timingDocumentation of baseline percent predicted FEV1 (ppFEV1) performed within the last 90 days

PurposeRequired for initiation and used as baseline for ongoing assessment

Provider Actions and Prior Authorization

Prior Authorization

Prior Authorization Required

Prior Authorization Required: Symdeko (tezacaftor/ivacaftor; ivacaftor) requires prior authorization. Providers must submit documentation supporting that the member meets all approval criteria. Failure to provide required documentation may result in denial of the request.

PA required for Symdeko
Approval duration per policy and line of business (see policy header/overview for specific duration)

Documentation Required

Provider Submission Requirements

Documentation Required: Providers must submit office chart notes, relevant laboratory results, genotype testing reports or sweat chloride results, and baseline ppFEV1 performed within the last 90 days. These documents must support that the member meets all listed approval criteria.

Office chart notes or clinical progress notes

Definitions and Reference Programs

inv-21: ppFEV1

DefinitionppFEV1 = percent predicted forced expiratory volume in 1 second

Baseline requirementBaseline ppFEV1 measurement is required and must be performed within the last 90 days before initiation

Use for continuationUsed to assess stabilization or improvement from baseline for continued therapy

inv-22: CFTR dysfunction

DefinitionCFTR dysfunction is demonstrated by either an elevated sweat chloride (≥ 60 mmol/L) or genetic testing confirming two disease-causing CFTR mutations (one from each parental allele)

Genotype relevancePresence of homozygous F508del or at least one CFTR mutation responsive to tezacaftor/ivacaftor supports therapy eligibility

Background

Tezacaftor/ivacaftor (Symdeko) combines a corrector and a potentiator: tezacaftor improves CFTR protein processing and trafficking (including certain F508del forms), while ivacaftor increases CFTR channel open probability. Together they increase CFTR quantity and function, resulting in enhanced chloride transport—consistent with the drug's indicated use in people with cystic fibrosis aged ≥6 years who are homozygous for F508del or who have at least one CFTR mutation responsive to tezacaftor/ivacaftor.

Policy Summary

Payermhn

PolicyTezacaftor/ivacaftor (Symdeko) for cystic fibrosis

Policy CodePolicy CP.PHAR.377

Change TypeCriteria revisions and dosing updates

Effective DateApr 3, 2018

Next Review Date

Key ActionSubmit prior authorization with documentation of CF diagnosis, baseline ppFEV1 within 90 days, genotype or sweat chloride, and absence of concurrent excluded CFTR modulators.

SourceLink

On This Page

Definition referenceppFEV1 = percent predicted forced expiratory volume in 1 second (Appendix A)

inv-11: Maximum daily dose by age/weight

Maximum daily dose — Age 6 to <12 years and <30 kgTezacaftor 50 mg / Ivacaftor 150 mg per day (one tezacaftor/ivacaftor tablet morning + one ivacaftor tablet evening)

Maximum daily dose — Age 6 to <12 years and ≥30 kgTezacaftor 100 mg / Ivacaftor 300 mg per day (one tezacaftor/ivacaftor tablet morning + one ivacaftor tablet evening)

Maximum daily dose — Age ≥12 yearsTezacaftor 100 mg / Ivacaftor 300 mg per day (same as adult regimen)

Dose modificationsReduce dose for moderate/severe hepatic impairment and when co-administered with moderate/strong CYP3A inhibitors

Lab results (including sweat chloride when available)

Genetic testing confirming two disease-causing CFTR mutations (one from each parental allele) or documentation of responsive mutation per Appendix D

Baseline percent predicted FEV1 (ppFEV1) within 90 days of request

Documentation Required

Required Clinical Documentation (ppFEV1 and Genetic Confirmation)

Required Clinical Evidence: For CF diagnoses, genetic confirmation requires two disease-causing CFTR mutations (one on each parental allele) OR elevated sweat chloride ≥ 60 mmol/L plus compatible clinical picture. Baseline ppFEV1 is required for initial approval (performed within the last 90 days).

Genetic testing confirming two disease-causing mutations (one from each parental allele)
Elevated sweat chloride ≥ 60 mmol/L as alternate evidence of CFTR dysfunction
Baseline ppFEV1 performed within last 90 days

Note

Recent Label Changes / Unlisted Uses

Label Changes or Unlisted Uses: If Symdeko has had a recent label change (within the last 6 months) not reflected in this policy, or the requested use (diagnosis, age, dosing) is not explicitly addressed here, follow the applicable formulary/non-formulary or off-label use policies for the member's line of business.

For formulary drugs: refer to the no coverage criteria policy for the relevant line of business (e.g., CP.CPA.190 commercial, HIM.PA.33 marketplace, CP.PMN.255 Medicaid)
For non-formulary drugs: refer to the non-formulary policy for the relevant line of business (e.g., CP.CPA.190 commercial, HIM.PA.103 marketplace, CP.PMN.16 Medicaid)
If use not listed and no recent label change applies: refer to off-label use policy (e.g., CP.CPA.09 commercial, HIM.PA.154 marketplace, CP.PMN.53 Medicaid)

Step Therapy

Step Therapy / Alignment Notes

Step Therapy and Criteria Alignment: Step therapy and continued therapy criteria align with other CFTR modulators. The initial approval criteria were revised to remove a specific ppFEV1 range requirement and now require documentation of baseline ppFEV1. Continued therapy criteria were revised to require stabilization or improvement (e.g., increase) in ppFEV1 from baseline rather than specific thresholds.

Step therapy aligns with other CFTR modulators; follow applicable step requirements if present
Initial criteria no longer require ppFEV1 between 40–90% — only a baseline ppFEV1 is required
Continued therapy requires stabilization or improvement in ppFEV1 from baseline

Denial Risk

Denial Risk — Concurrent Use and Missing Documentation

Concurrent Modulator Exclusion and Denial Risk: Symdeko must not be prescribed concurrently with other CFTR modulators (examples include Alyftrek, Kalydeco, Orkambi, Trikafta). Requests that indicate concurrent use with excluded CFTR modulators or that lack supporting documentation for approval criteria are at risk for denial.

Do not combine Symdeko with other CFTR modulators (e.g., Alyftrek, Kalydeco, Orkambi, Trikafta)
Incomplete submission (missing office notes, labs, genotype, or baseline ppFEV1) may lead to denial

DocumentationGenetic testing and mutation documentation referenced in appendix and CFF MAP for testing support

inv-23: CFF MAP

Program nameCystic Fibrosis Foundation Mutation Analysis Program (CFF MAP)

PurposeFree, confidential genetic testing program for people with suspected or confirmed CF

Policy linkageProviders are directed to CFF MAP for mutation testing to confirm CFTR mutations as required by policy

inv-24: ppFEV1 (repeat)

Primary useppFEV1 is used as the baseline lung function measure and to assess stabilization or improvement for continued therapy

Baseline timingBaseline ppFEV1 must be documented within the last 90 days before initiation

Clinical noteppFEV1 defined as percent predicted FEV1 (Appendix A) and is the metric referenced for response assessment