ModifiedCignaPolicy IP0433

Cystic Fibrosis - Symdeko

Policy governs prior authorization and coverage criteria for Symdeko (tezacaftor/ivacaftor and ivacaftor) for treatment of cystic fibrosis in eligible patients, affecting prescribers and prior authorization reviewers under Cigna-administered plans.

Policy Summary

PayerCigna

PolicyCystic Fibrosis - Symdeko

Policy CodePolicy IP0433

Change TypeCriteria revisions and preferred product updates

Effective Date

Next Review Date

Key ActionSubmit prior authorization with documentation of genetic variant or prescriber attestation of inadequate efficacy or significant intolerance to Trikafta when preferred product criteria apply.

SourceLink

POLICY UPDATE CHANGES

Updated coverage policy title from Tezacaftor/Ivacaftor to Cystic Fibrosis - Symdeko and added documentation requirement language.

Added preferred product criterion allowing coverage of Symdeko for specific CFTR mutations (711+3A>G, E831X, 2789+5G>A, 3272-26A>G, 3849+10kbC>T).

Preferred product table criteria modified to require inadequate efficacy or significant intolerance to Trikafta (rather than simple failure/contraindication).

Specified infertility as a condition not recommended for approval.

Changed language from 'mutation' to 'variant' throughout CFTR-related criteria and requirements.

Preferred product table updated to require trial and inadequate efficacy or significant intolerance to Trikafta (or pathogenic variant not covered by Trikafta) rather than prior explicit mutation list.

≥6minimum age for Symdeko indication

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1 yrstandard approval duration

5new responsive mutations (example)

Total Savingsapplies to plan type

Infertilitynew not-recommended condition

Coverage Criteria for Symdeko (tezacaftor/ivacaftor & ivacaftor)

Initial Therapy — Approve for 1 year

Approve for 1 year if the patient meets ALL of the following (A, B, C, D, E, and F):

A: Patient is ≥ 6 years of age

(i): Patient has at least ONE pathogenic or likely pathogenic CFTR variant listed in the policy (documentation required for certain variants)
See policy variant lists
(ii): Patient has TWO copies of the F508del variant

C: Patient has at least ONE of: positive newborn cystic fibrosis screening test, family history of cystic fibrosis, or clinical presentation consistent with cystic fibrosis (examples include meconium ileus, sinopulmonary symptoms such as persistent cough or wheezing, pulmonary function tests consistent with obstructive airway disease, excess sputum production, bronchiectasis, sinusitis, failure to thrive, pancreatic insufficiency)

D: Evidence of abnormal CFTR function as demonstrated by at least ONE of: elevated sweat chloride test; two cystic fibrosis–causing CFTR variants; or abnormal nasal potential difference

E: Medication is prescribed by or in consultation with a pulmonologist or a physician who specializes in the treatment of cystic fibrosis

F: Preferred product criteria is met for applicable plans (see Preferred Product Table).

Applies to Total Savings Drug List Plans where noted; may require documentation of prior trial and inadequate efficacy or significant intolerance to elexacaftor/tezacaftor/ivacaftor (Trikafta) or demonstration that the patient has a pathogenic/likely pathogenic CFTR variant not covered by Trikafta

Updated coverage criteria and preferred product logic

Policy criteria revisions and preferred product requirements as of revisions:

Preferred Product Requirement: Patient has tried and, according to the prescriber, has experienced inadequate efficacy OR a significant intolerance with elexacaftor/tezacaftor/ivacaftor (Trikafta™) (tablets or oral granules) OR patient has at least one pathogenic or likely pathogenic CFTR variant that is not covered by Trikafta.N/A

May require prior authorization; applies to Total Savings Drug List Plans.

Documentation is provided that the patient meets one of the listed criteria (e.g., genetic variant, prior treatment response).N/A

Documentation may include chart notes, laboratory tests, medical test results, claims records, and/or other information as noted in the policy.

Terminology Change: Criteria language was updated to replace the term 'mutation' with 'variant' for requirements referencing CFTR gene changes (e.g., presence of ≥1 pathogenic/likely pathogenic CFTR variant, two copies of F508del, or two CF-causing CFTR variants).

Symdeko for any use not matching the FDA‑approved indications or the policy’s stated criteria is considered not medically necessary. This includes use in patients with an unknown CFTR genotype when recommended diagnostic testing (FDA‑cleared CF mutation testing with sequencing verification as indicated) has not been performed, and other non‑indicated uses described in the policy revision history.

The policy revisions clarify that patients with an unknown CFTR genotype should undergo the recommended testing workflow before Symdeko is considered, and that use outside those parameters is not covered under the medical necessity standard.

Infertility is explicitly listed in the policy revisions as a condition not recommended for approval for Symdeko. The change was added to the Conditions Not Recommended for Approval section during the annual revision process.

Providers requesting Symdeko for infertility should expect denial under this policy and are directed to follow the stated appeal/coverage exception processes where applicable.

Combination therapy of Symdeko with other cystic fibrosis transmembrane conductance regulator (CFTR) modulators is listed as a condition that is not covered. The policy refers to the class of other CFTR modulators rather than enumerating only individual agents, making concurrent use with any other CFTR modulator outside the approved single‑agent indication unsupported.

This position applies to employer plan guidance and to the broader exclusions recorded in the revision notes; prior authorization reviewers should deny requests proposing concomitant CFTR modulator therapy per the exclusion language.

Combination therapy with other CFTR modulators (examples provided in the policy such as Alyftrek, Kalydeco, Orkambi, and Trikafta) is specifically called out as not medically necessary. The policy lists these examples to illustrate the class‑level exclusion for concurrent CFTR modulator therapy.

Requests for Symdeko in combination with any of the example agents should be considered non‑covered and processed accordingly.

Use of Symdeko for the treatment of infertility is reiterated in the revision summary as a condition for which coverage is not recommended. This revision was added to the Conditions Not Recommended for Approval and appears in the annual revision notes.

Authorization requests citing infertility as the indication for Symdeko should be denied under this policy’s stated exclusions.

The policy now lists Cystic Fibrosis, Patient with Unknown Cystic Fibrosis Transmembrane Conductance Regulator Gene Variant (previously referenced using the term 'mutation') among conditions not recommended for approval unless the recommended genotype testing and verification are completed. The document terminology has been updated from 'mutation' to variant throughout the CFTR‑related criteria.

When a patient’s CFTR genotype is unknown, the policy requires an FDA‑cleared mutation test with bidirectional sequencing as recommended by the test instructions before Symdeko may be considered; absent that documentation, coverage is not recommended.

Coding and Diagnostic Thresholds

Covered CPT Codesmixed

No codes listed

Sweat chloride diagnostic thresholds

Diagnostic threshold indicating cystic fibrosisSweat chloride ≥ 60 mmol/L establishes a CF diagnosis.

Diagnostic threshold making CF unlikelySweat chloride < 30 mmol/L — a diagnosis of CF is unlikely (unless other confirmatory testing supports CF).

Indeterminate range requiring further testingSweat chloride 30–59 mmol/L (≥30 to <60 mmol/L) — perform CFTR genetic analysis and, if needed, full gene sequencing or physiologic testing (NPD/ICM).

Provider Actions, Prior Authorization, and Documentation

Prior Authorization

Prior Authorization Required

Prior Authorization is required for benefit coverage of Symdeko. All approvals are provided for the duration noted in the policy (standardly 1 year). Because of the specialized skills required for evaluation and diagnosis of patients treated with Symdeko as well as the monitoring required for adverse events and efficacy, approval requires Symdeko to be prescribed by or in consultation with a physician who specializes in the condition being treated.

Approvals are typically provided for 1 year.
Prescriber requirement: specialist in the condition being treated (or consultation).

Step Therapy

Preferred Product Criteria (Employer Plans)

For employer Total Savings Drug List plans, Symdeko (tezacaftor/ivacaftor and ivacaftor tablets) is a preferred-product-managed agent with specific criteria. Coverage may be approved when the patient meets ONE of the following: 1) the patient has tried Trikafta (elexacaftor/tezacaftor/ivacaftor tablets or oral granules) and, according to the prescriber, experienced inadequate efficacy OR a significant intolerance to Trikafta; 2) the patient has at least one CFTR gene variant considered pathogenic or likely pathogenic that is not covered by Trikafta (tablets or granules); or 3) the patient has already been started on therapy with Symdeko. These preferred-product criteria apply to Total Savings Drug List Plans and may require prior authorization and documentation.

Background on Symdeko and Indications

Symdeko (tezacaftor/ivacaftor and ivacaftor) is a cystic fibrosis transmembrane conductance regulator (CFTR) modulator indicated for the treatment of cystic fibrosis in patients aged ≥ 6 years who are homozygous for the F508del variant or who have at least one CFTR variant responsive to tezacaftor/ivacaftor based on clinical or in vitro evidence. Prior Authorization is required and approvals are generally provided for a duration of 1 year.

The policy’s background and approval criteria emphasize confirmation of the patient’s CFTR variant status and evidence of CFTR dysfunction (for example, elevated sweat chloride or physiologic testing) as part of meeting medical necessity for Symdeko.

Definitions and Terminology

Responsive mutation

Definition of responsive mutationA CFTR gene mutation that produces CFTR protein and is shown by clinical FEV1 response or in vitro data to increase chloride transport to ≥10% of untreated normal over baseline and listed in Table 1.

Evidence types acceptedClinical FEV1 response and/or in vitro data (Fischer rat thyroid cells) demonstrating ≥10% increase in chloride transport over baseline.

Listing locationResponsive mutations are enumerated in Table 1 of the policy (Table 1 lists CFTR gene mutations that produce CFTR protein and are responsive to Symdeko).

Use of the term 'variant'

Terminology changeThe policy replaces the term 'mutation' with 'variant' for CFTR gene descriptors (e.g., 'pathogenic/likely pathogenic CFTR variant').

Affected requirements

Policy Summary

PayerCigna

PolicyCystic Fibrosis - Symdeko

Policy CodePolicy IP0433

Change TypeCriteria revisions and preferred product updates

Effective Date

Next Review Date

SourceLink

On This Page

Terminology change reflected across specified approval criteria.

Conditions Not Recommended/Not Covered: Policy revisions clarified that use of Symdeko for infertility and combination therapy with other CFTR modulators are conditions not recommended for approval or not covered; combination therapy language now refers to the class of CFTR modulators (examples listed).N/A

Preferred Product Table Scope: Preferred Product Table applies to Total Savings Drug List Plans and includes the updated preferred product logic requiring prescriber attestation of inadequate efficacy or significant intolerance to Trikafta or presence of a pathogenic/likely pathogenic variant not covered by Trikafta.N/A

Failure to document prior trial and inadequate efficacy or significant intolerance to Trikafta or lack of qualifying variant may trigger denial when preferred product criteria apply.

Applies to: Employer Plans — Total Savings Drug List Plans.
Allowed when ONE of the following is met: (1) prior trial of Trikafta with inadequate efficacy OR significant intolerance; (2) at least one pathogenic/likely pathogenic CFTR variant not covered by Trikafta; (3) patient already started on Symdeko therapy.
May require prior authorization and documentation to support the criterion selected.

Step Therapy

Step Therapy vs Trikafta

Step-therapy preference for Trikafta is implied in the preferred-product criteria: coverage of Symdeko may require a prior trial of Trikafta with documented inadequate efficacy or significant intolerance before Symdeko is approved. Exceptions include patients with CFTR variants not eligible for Trikafta or those already on Symdeko therapy. Documentation supporting prior trial, inadequate efficacy, or intolerance is required when indicated.

Symdeko coverage may require documented trial and inadequate efficacy or significant intolerance to Trikafta (tablets or oral granules).
Exception if patient has a pathogenic/likely pathogenic CFTR variant not covered by Trikafta.
Exception if patient is currently receiving Symdeko.

Documentation Required

Documentation is required where noted in the criteria. Documentation may include, but is not limited to, chart notes, laboratory tests, medical test results, claims records, and/or other information. All documentation must include patient-specific identifying information.

Provide documentation of prior trial and outcome (efficacy or intolerance) when required by the criteria.
Provide genetic testing results when claiming a CFTR variant not covered by Trikafta.
All documentation must include patient identifiers and may be requested during prior authorization review.

Denial Risk

Denial Triggers

Claims submitted without covered diagnosis/procedure codes or not accompanied by covered codes under the applicable Coverage Policy will be denied as not covered. Failure to document prior trial with and inadequate efficacy or significant intolerance to elexacaftor/tezacaftor/ivacaftor (Trikafta) or lack of documentation supporting a non-Trikafta-eligible CFTR variant may trigger denial.

Denial risk if required documentation or covered codes are missing.
Denial risk if prior trial of Trikafta is not documented when required by plan criteria.

The change from 'mutation' to 'variant' applies to requirements such as presence of ≥1 pathogenic/likely pathogenic CFTR variant, two copies of F508del, and two CF-causing CFTR variants demonstrating abnormal CFTR function.

Documentation noteReferences to conditions not recommended for approval (e.g., unknown CFTR gene variant) also reflect the terminology change from 'mutation' to 'variant'.