Currentmedical mutual - ohioPolicy N/A

Alyftrek (Vanzacaftor/Tezacaftor/Deutivacaftor) Tablets

Defines prior authorization criteria, documentation, and coverage stance for Alyftrek for treatment of cystic fibrosis in patients aged ≥6 years with at least one responsive CFTR mutation; applies to pharmacy benefit determinations.

Policy Summary

Payermedical mutual - ohio

PolicyAlyftrek (Vanzacaftor/Tezacaftor/Deutivacaftor) Tablets

Policy CodePolicy N/A

Change TypeAnnual review — no material changes

Effective DateN/A

Next Review DateMar 20, 2025

Key ActionObtain prior authorization and confirm patient meets authorization criteria, including age ≥6, at least one responsive CFTR mutation, specialist involvement, and evidence of abnormal CFTR function.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

≥6minimum patient age for coverage

6 moinitial authorization duration

1 yrextended authorization duration

responsive mutationgenotype requirement

≥6 mo + responsecontinuation criteria

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Coverage / Medical Necessity Criteria

FDA-Approved Indication - Initial Use

Approve for 6 months (can be extended to 12 months based on patient's response) if ALL of the following (A, B, C, D, and E) are met:

Initial Authorization Criteria

A: Patient is ≥ 6 years of age
B: Medication is prescribed by or in consultation with a pulmonologist or a physician who specializes in the treatment of cystic fibrosis
C: Patient has at least ONE pathogenic or likely pathogenic CFTR variant listed as responsive in the policy mutation lists
D: Patient has at least ONE of the following: positive newborn cystic fibrosis screening test; OR family history of cystic fibrosis; OR clinical presentation consistent with signs and symptoms of cystic fibrosis (examples include but are not limited to meconium ileus, sinopulmonary symptoms such as persistent cough or wheezing, bronchiectasis, sinusitis, failure to thrive, pancreatic insufficiency)
E: Patient has evidence of abnormal CFTR function demonstrated by at least ONE of: elevated sweat chloride test; OR two cystic fibrosis–causing CFTR mutations; OR abnormal nasal potential difference

Duration: Initial approval duration: 6 months; may be extended to 12 months based on patient response

Continuation of Therapy

Patient must meet the following criteria (A, B, and C):

Continuation Criteria

A: Patient continues to meet all initial start criteria (see Initial Authorization Criteria)
B: Patient has been using Alyftrek for at least 6 months
C: Patient has experienced an adequate response to therapy compared to baseline (for example: improvement in FEV1 or other lung function tests, improvement in sweat chloride, decreased pulmonary exacerbations or infections, increased weight, decreased hospitalizations)

Extended Approval Duration: Extended approval duration: 1 year for patients meeting continuation criteria

Coverage of Alyftrek is not recommended for patients with an unknown CFTR gene mutation. An FDA-cleared cystic fibrosis mutation test should be used to confirm the presence of at least one indicated responsive mutation prior to use. Coverage is also not recommended for use as infertility treatment or for other indications not explicitly listed in the policy's recommended authorization criteria.

Alyftrek should not be used in combination with other CFTR modulators. Because Alyftrek contains tezacaftor, concurrent use with agents such as Symdeko®, Trikafta®, Kalydeco®, or Orkambi® is prohibited. Patients without a detected responsive CFTR mutation (unknown genotype) should not be started on Alyftrek; an FDA-cleared CF mutation test is required to verify an indicated mutation before therapy.

Provider Requirements, Authorization, and Documentation

Prior Authorization

Prior Authorization Required

Prior authorization is required for pharmacy benefit coverage of Alyftrek. Initial requests must include sufficient documentation to allow review; initial approvals are granted for the durations noted in the policy and reauthorization requires demonstration of response to therapy. Prescriptions for initial therapy should be written by or in consultation with a pulmonologist or a clinician who specializes in cystic fibrosis.

Prior authorization required for pharmacy benefit
Initial therapy: prescriber must be pulmonologist or CF specialist
Reauthorization requires documented response to therapy

Note

Approval Durations

Initial approvals are issued for 6 months. If response to therapy is demonstrated, extended approvals may be granted for up to 1 year.

Initial approval duration: 6 months
Extended approval duration: 1 year

Key Definitions and Diagnostic Criteria

inv-11: Evidence of abnormal CFTR function

Elevated sweat chloride testDemonstrated by an elevated sweat chloride test

Two CF-causing CFTR mutationsDocumentation of two cystic fibrosis–causing CFTR mutations

Abnormal nasal potential differenceDemonstration of abnormal nasal potential difference

inv-12: Responsive CFTR mutation

Pathogenic or likely pathogenic variantA CFTR gene variant considered pathogenic or likely pathogenic

Listed in responsive mutation tablesVariant must be listed in the policy's responsive CFTR mutation tables based on clinical response and/or in vitro data

Background / Drug Description

Alyftrek is a fixed‑combination CFTR modulator containing deutivacaftor, tezacaftor, and vanzacaftor indicated for treatment of cystic fibrosis in patients aged ≥ 6 years who have at least one F508del or other responsive CFTR mutation. The policy notes limited or preliminary data and safety concerns for uses outside the labeled indication and specifies genotyping confirmation prior to therapy.

Policy Summary

Payermedical mutual - ohio

PolicyAlyftrek (Vanzacaftor/Tezacaftor/Deutivacaftor) Tablets

Policy CodePolicy N/A

Change TypeAnnual review — no material changes

Effective DateN/A

Next Review DateMar 20, 2025

SourceLink

On This Page

Denial Risk

Prohibition on Combination CFTR Modulator Therapy

Concurrent use of Alyftrek with other CFTR modulator products is not recommended. Alyftrek contains tezacaftor and therefore should not be used in combination with other tezacaftor-containing or other CFTR modulator regimens (examples include Kalydeco®, Orkambi®, Symdeko®, Trikafta®).

Do not prescribe Alyftrek with other CFTR modulators (e.g., Kalydeco®, Orkambi®, Symdeko®, Trikafta®)
Alyftrek contains tezacaftor — avoid combinations with tezacaftor-containing products

Documentation Required

Documentation to Support Medical Necessity

Submit the following documentation with authorization requests to support medical necessity. The Company may request additional records as needed and may deny based on insufficiency of documentation.

Relevant clinical records demonstrating diagnosis and symptoms consistent with cystic fibrosis (e.g., chronic sinopulmonary symptoms, bronchiectasis, failure to thrive)
Documentation of CFTR genotype showing at least one pathogenic or likely pathogenic variant (FDA-cleared mutation test results)
Evidence of abnormal CFTR function: elevated sweat chloride, two CF-causing CFTR mutations, or abnormal nasal potential difference
Provider credentials or documentation of consultation with a pulmonologist or CF specialist
Previous therapy details and documentation of response for reauthorization requests
Any additional test results or records requested by the Company

Denial Risk

Potential Denial Reasons

Requests may be denied for lack of medical necessity, investigational or experimental use, not being within the member’s benefit, or insufficient documentation. Specific common denial reasons include the absence of an indicated CFTR mutation, use in combination with other CFTR modulators, requests for non‑FDA‑approved indications (e.g., infertility), and failure to provide requested medical records or test results.

Not medically necessary or not within scope of benefits
Investigational or experimental use / condition not recommended for approval
Combination therapy with other CFTR modulators
No documentation of an indicated CFTR mutation or insufficient genetic/test evidence
Insufficient clinical documentation or failure to provide requested records

Confirmed by FDA‑cleared test when genotype unknown

If genotype is unknown, an FDA‑cleared CF mutation test should be used to confirm presence of an indicated mutation