ModifiedCignaPolicy N/A

Cystic Fibrosis Transmembrane Conductance Regulator - Alyftrek Prior Authorization Policy

Defines prior authorization requirements and coverage criteria for Alyftrek for treatment of cystic fibrosis in eligible patients, for Cigna-administered health benefit plans.

Policy Summary

PayerCigna

PolicyAlyftrek prior authorization for cystic fibrosis

Policy CodePolicy N/A

Change TypeNew policy

Effective DateN/A

Next Review DateJan 2, 2025

Key ActionObtain prior authorization and document patient age (≥6 years), at least one responsive CFTR variant, evidence of abnormal CFTR function, and prescriber specialty.

SourceLink

POLICY UPDATE CHANGES

New Policy for Alyftrek with FDA-approved indications and coverage criteria for cystic fibrosis.

1 yearinitial approval duration

≥6minimum patient age

multi-pageresponsive mutations

3example exclusions

Coverage Criteria for Alyftrek (vanzacaftor/tezacaftor/deutivacaftor)

FDA-Approved Indication (Initial approval)

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

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

B: Patient has at least ONE of the listed pathogenic or likely pathogenic CFTR variants (extensive list of responsive variants is provided in the policy document).at least one listed variant

Variants enumerated across policy chunks 19-22

C: Patient meets at least ONE of: 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 include meconium ileus, sino-pulmonary symptoms such as persistent cough or wheezing, bronchiectasis, sinusitis, failure to thrive, pancreatic insufficiency).1 of 3

D: Patient has evidence of abnormal CFTR function demonstrated by at least ONE of: i. Elevated sweat chloride test; OR ii. Two CF-causing CFTR mutations; OR iii. Abnormal nasal potential difference.1 of 3

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

No specific exclusions are enumerated in this document fragment. Clinical guidance notes that where indications overlap, Trikafta is generally recommended over other CFTR modulators. Providers should consider current CFTR-modulator treatment standards and select the agent whose FDA-approved indications and age ranges best match the patient’s genotype and clinical situation.

Use of Alyftrek in the following situations is considered experimental, investigational, or unproven and is excluded from coverage: (1) patients with an unknown CFTR gene mutation — an FDA-cleared CF mutation test should be used to confirm an indicated mutation prior to use; (2) concurrent combination therapy with other CFTR modulators (examples include Kalydeco, Orkambi, Symdeko, Trikafta); and (3) use for infertility. This list is not exhaustive and may be updated as new evidence becomes available.

This policy fragment does not include any explicitly labeled list of conditions designated as not medically necessary. Guidance instead highlights preferred agents (for example, Trikafta where indications overlap) but does not state specific not-medically-necessary scenarios in this excerpt.

Alyftrek is considered not covered/experimental for any use other than the FDA-approved cystic fibrosis indications described in this policy. Examples explicitly listed include use without documented eligible CFTR mutations, concurrent use with other CFTR modulators, and use for infertility.

Provider Actions, Prior Authorization, and Documentation

Prior Authorization

Prior Authorization Required

Prior authorization is required for Alyftrek. Approvals are provided for 1 year when the criteria below are met. Because of the specialized skills required for evaluation and diagnosis and for monitoring adverse events and long-term efficacy, Alyftrek must be prescribed by or in consultation with a physician who specializes in the treatment of cystic fibrosis. Lack of prior authorization may result in coverage denial if requirements are not met.

Approval duration: 1 year when criteria met
Prescriber requirement: Prescribed by or in consultation with a pulmonologist or physician who specializes in cystic fibrosis

Documentation Required

Eligibility Criteria (Age and Genotype)

Approval requires documentation that the patient meets age and genotype eligibility criteria and evidence of CFTR dysfunction. If the patient's CFTR genotype is unknown, an FDA-cleared CF mutation test should be used to confirm the presence of at least one indicated pathogenic or likely pathogenic CFTR variant responsive to Alyftrek.

Age: Patient is ≥ 6 years of age
Genotype: At least ONE pathogenic or likely pathogenic CFTR variant listed in the FDA-approved indication
If genotype unknown: perform an FDA-cleared CF mutation test to confirm an indicated mutation
Required documentation: patient age, documentation of at least one listed pathogenic/likely pathogenic CFTR variant, and evidence of CFTR dysfunction (see criteria)

Denial Risk

Triggers for Denial

Alyftrek is considered experimental/investigational and may be denied when used in situations not meeting the FDA-approved criteria below.

Use in patients with unknown CFTR mutation without documentation of an indicated mutation
Use in combination with other CFTR modulators (see restriction below)
Use for infertility

Denial Risk

Combination Therapy Restriction

Combination use of Alyftrek with other CFTR modulators is not allowed. Because Alyftrek contains tezacaftor, coadministration with other modulators that include tezacaftor, elexacaftor, ivacaftor, lumacaftor, or similar CFTR modulators (for example Kalydeco, Orkambi, Symdeko, Trikafta) is disallowed and may result in denial.

Do not prescribe Alyftrek together with Kalydeco (ivacaftor), Orkambi (lumacaftor/ivacaftor), Symdeko (tezacaftor/ivacaftor), Trikafta (elexacaftor/tezacaftor/ivacaftor), or other CFTR modulators
Prior authorization should reflect and enforce this combination therapy restriction

Background and Therapeutic Context

Alyftrek is a combination CFTR modulator tablet containing deutivacaftor, tezacaftor, and vanzacaftor indicated for the treatment of cystic fibrosis in patients aged ≥ 6 years who have at least one F508del or other responsive CFTR mutation. Diagnosis of cystic fibrosis is typically supported by clinical presentation together with evidence of CFTR dysfunction (for example, elevated sweat chloride or genetic testing). Prior authorization is required and approvals are provided for 1 year when the FDA‑approved coverage criteria are met.

Definitions

Alyftrek (definition)

Active ingredientsDeutivacaftor, tezacaftor, and vanzacaftor combination tablet

Therapeutic classCFTR modulator (combination potentiator/corrector)

Indication (summary)Treatment of cystic fibrosis in patients aged ≥ 6 years with at least one F508del or other responsive CFTR mutation

Prescription testing guidanceIf genotype unknown, use an FDA‑cleared CF mutation test to confirm at least one indicated mutation

Cystic fibrosis (CF) diagnosis

Diagnostic requirementsClinical presentation consistent with cystic fibrosis PLUS evidence of CFTR dysfunction

Sweat chloride thresholdSweat chloride ≥ 60 mmol/L establishes CF diagnosis

Sweat chloride interpretationSweat chloride < 30 mmol/L makes CF unlikely; 30–59 mmol/L requires genetic analysis

Diagnostic testing sequenceRecommend sweat chloride testing first, then CFTR genetic analysis, then CFTR physiologic tests (NPD or ICM) as needed

Demonstration of abnormal CFTR function

Sweat chloride testElevated sweat chloride test consistent with CFTR dysfunction (e.g., ≥ 60 mmol/L)

Genetic evidenceTwo CF‑causing CFTR mutations identified on genetic analysis

Physiologic testingAbnormal nasal potential difference (NPD) demonstrating CFTR dysfunction

When to perform additional testingIf genotype undefined or single variant found, perform full gene sequencing or physiologic testing (NPD or ICM)

OpenPayer

Cystic Fibrosis Transmembrane Conductance Regulator - Alyftrek Prior Authorization Policy

Coverage Criteria for Alyftrek (vanzacaftor/tezacaftor/deutivacaftor)

Provider Actions, Prior Authorization, and Documentation

Background and Therapeutic Context

Definitions

Revision History