ModifiedCignaPolicy IP0723

Cystic Fibrosis Transmembrane Conductance Regulator - Alyftrek

This policy governs prior authorization and coverage criteria for Alyftrek for treatment of cystic fibrosis in Cigna-administered benefit plans, specifying FDA‑approved indications, required documentation, prescriber specialty, and product-preference rules.

Policy Summary

PayerCigna

PolicyCystic Fibrosis Transmembrane Conductance Regulator - Alyftrek

Policy CodePolicy IP0723

Change TypeNew policy

Effective Date

Next Review Date

Key ActionObtain prior authorization and document an FDA‑cleared CFTR mutation test showing at least one responsive mutation; approvals are for 1 year and prescriber must be a pulmonologist or CF specialist.

SourceLink

POLICY UPDATE CHANGES

New policy created for Alyftrek with coverage criteria and exclusions.

≥6minimum FDA-approved patient age

1 yearinitial approval duration

ExtensiveCFTR responsive mutations enumerated

Prior Authrequirement for coverage

2approval pathways

Policy Summary

PayerCigna

PolicyCystic Fibrosis Transmembrane Conductance Regulator - Alyftrek

Policy CodePolicy IP0723

Change TypeNew policy

Effective Date

Next Review Date

SourceLink

On This Page

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

Coverage Criteria for Alyftrek

Initial Approval — FDA‑Approved Indication

Approve for 1 year if the patient meets ALL of the following (A–F):

A: Age: Patient is ≥ 6 years of age.>= 6 years

B: Genotype: Documentation is provided that the patient has at least ONE listed pathogenic or likely pathogenic CFTR variant responsive to Alyftrek.presence of >=1 responsive CFTR variant

Extensive mutation list provided in policy (see policy for specific variants).

C: Clinical presentation consistent with cystic fibrosis: Patient meets at least ONE of the following: (i) positive cystic fibrosis newborn screening test; OR (ii) family history of cystic fibrosis; OR (iii) clinical presentation consistent with signs and symptoms of cystic fibrosis (examples: 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).one of (i,ii,iii)

D: Evidence of CFTR dysfunction: Patient has at least ONE of: (i) elevated sweat chloride test; OR (ii) two cystic fibrosis–causing CFTR mutations; OR (iii) abnormal nasal potential difference.one of (i,ii,iii)

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

F: Preferred product criteria: Product-specific preferred criteria is met for the product(s) as listed in the plan-specific tables.plan-specific preference met

For Employer and Individual/Family plans this includes either prior trial and inadequate efficacy or significant intolerance to Trikafta (tablets or oral granules) OR patient already on Alyftrek.

Initial Coverage Criteria

Covered when ONE of the following is met:

Primary coverage pathways: (1) The patient has tried Trikafta (tablets or oral granules) and, according to the prescriber, experienced inadequate efficacy OR a significant intolerance; OR (2) the patient has already been started on therapy with Alyftrek.n/a

Trikafta oral granules count as prior trial.

Use of Alyftrek when the patient’s CFTR gene mutation is unknown is not covered. An FDA‑cleared cystic fibrosis mutation test should be used to detect the presence of at least one indicated mutation prior to initiating Alyftrek.

Combination therapy of Alyftrek with other CFTR modulators is considered not medically necessary. Examples of other CFTR modulators include Kalydeco® (ivacaftor), Orkambi® (lumacaftor/ivacaftor), Symdeko® (tezacaftor/ivacaftor), and Trikafta® (elexacaftor/tezacaftor/ivacaftor).

Use of Alyftrek for infertility or any other non‑FDA approved indication is considered not medically necessary and is not covered.

Alyftrek is not covered for patients with an unknown CFTR gene mutation unless an FDA‑cleared cystic fibrosis mutation test demonstrates at least one indicated mutation prior to therapy.

Alyftrek is covered only for the FDA‑approved cystic fibrosis indication when the patient has a documented eligible CFTR mutation and evidence of CFTR dysfunction; use for any other indication is considered not medically necessary.

Use of Alyftrek for any purpose other than the criteria specified in this policy is considered not medically necessary, including use in patients with unknown CFTR mutation status and combination therapy with other CFTR modulators.

Age and Indication Coding Notes

Minimum age per indication

Minimum age≥ 6 years

Approval durationInitial approvals provided for 1 year

Indication age basisPolicy and prescribing information specify ≥ 6 years for CF patients with at least one F508del or other responsive CFTR mutation

Provider Requirements, Prior Authorization, and Documentation

Prior Authorization

Prior Authorization Required

Prior authorization is required for Alyftrek. Approvals are provided for 1 year. Alyftrek must be prescribed by or in consultation with a physician who specializes in cystic fibrosis (e.g., pulmonologist) due to the specialized evaluation and monitoring required.

Prior authorization required for prescription benefit coverage
Approval duration: 1 year
Prescriber requirement: prescribed by or in consultation with a physician who specializes in the condition being treated (pulmonologist or CF specialist)

Documentation Required

Documentation is required where noted in the criteria to support the medical necessity of therapy. Acceptable documentation includes, but is not limited to, chart notes, laboratory tests, claims records, and other clinical information.

Provide clinical chart notes supporting diagnosis and rationale for therapy

Background on Alyftrek

Alyftrek is a triple‑combination CFTR modulator containing deutivacaftor, tezacaftor, and vanzacaftor, indicated for the treatment of cystic fibrosis in patients aged ≥ 6 years who have at least one F508del or another responsive CFTR mutation. Treatment with Alyftrek is intended for patients with documented eligible mutation(s) and clinical or physiologic evidence of CFTR dysfunction; genotype testing with an FDA‑cleared mutation test is required when mutation status is unknown.

Definitions and Diagnostic Criteria

Evidence of CFTR dysfunction

Sweat chlorideElevated sweat chloride test (≥ 60 mmol/L supports CF diagnosis)

Genetic evidenceIdentification of two CF-causing CFTR mutations (or genotype showing CF-causing variants)

Physiologic testingAbnormal nasal potential difference (NPD) demonstrating CFTR dysfunction

Responsive CFTR mutation

DefinitionA CFTR gene mutation demonstrated to respond to therapy as identified by an FDA‑cleared cystic fibrosis mutation test

Source of determinationResponsive mutations listed based on clinical response, in vitro data, or extrapolation (see policy Table 1)