ModifiedUnitedHealthcarePolicy N/A

Alyftrek (vanzacaftor/tezacaftor/deutivacaftor) prior authorization

Defines UnitedHealthcare Pharmacy prior authorization and medical necessity criteria for Alyftrek for members aged ≥6 years with responsive CFTR mutations, including initial authorization, reauthorization, and provider requirements.

Policy Summary

PayerUnitedHealthcare

PolicyAlyftrek (vanzacaftor/tezacaftor/deutivacaftor) prior authorization

Policy CodePolicy N/A

Change TypeModified clinical criteria (step therapy update)

Effective DateJul 1, 2025

Next Review DateN/A

Key ActionSubmit laboratory results documenting at least one CFTR mutation responsive to Alyftrek or documentation of Trikafta trial/failure, contraindication, or intolerance as applicable.

SourceLink

POLICY UPDATE CHANGES

Updated criteria to require history, contraindication, or intolerance to Trikafta, or member is currently on Alyftrek therapy.

Added reference to Alyftrek package insert (December 2024).

Added reference to Trikafta package insert (December 2024).

≥6minimum patient age for coverage

12 moauthorization period length

CFTR testgenotype documentation required

Trikafta trialprior treatment requirement or exception

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Coverage Criteria for Alyftrek

Initial Authorization

Covered when ALL of the following are met for initial authorization

Initial Authorization: Patient has a diagnosis of cystic fibrosis (CF).

Genotype documentation: Submission of laboratory results documenting at least one CFTR gene mutation responsive to Alyftrek (examples: F508del; mutations responsive based on clinical, in vitro, or extrapolated data). Refer to the Alyftrek Prescribing Information for a complete, up-to-date list of responsive mutations.

Age requirement: Patient is ≥ 6 years of age.

One of the following must be met

Option 1: Submission of medical records demonstrating a history of trial and failure, contraindication, or intolerance to Trikafta (elexacaftor/tezacaftor/ivacaftor).
Option 2: Patient has a documented CFTR gene mutation that is responsive to Alyftrek but is not responsive to Trikafta (see Trikafta Prescribing Information for responsive mutations).
Option 3 - Current Alyftrek use
- 3a: Patient is currently on Alyftrek therapy as documented by claims history or submission of medical records (document date and duration of therapy).
- 3b: Patient has not established therapy via a manufacturer-supplied sample or via Vertex assistance/co-pay programs (e.g., GPS program) used to initiate therapy.

Prescriber requirement: Prescribed by or in consultation with a provider who specializes in the treatment of cystic fibrosis.

Reauthorization

Covered when ALL of the following are met for reauthorization

Reauthorization: Documentation of positive clinical response to Alyftrek therapy (for example, improved or stable lung function).

Authorization duration: Authorization is issued for 12 months; state mandates and member-specific benefit plan coverage may affect approval. UnitedHealthcare may consider claim/medication history and diagnosis codes in automated approval processes.

For patients who are already receiving Alyftrek, documentation must show they are a true established user. Submit claims history or medical records documenting the date and duration of therapy and an attestation that the therapy was not initiated via a manufacturer-supplied sample or through Vertex assistance/co-pay programs. If the patient’s therapy was started using a manufacturer sample or any Vertex GPS or co-pay assistance program, the patient must meet the initial authorization criteria as if they were new to therapy.

Coverage decisions for Alyftrek may be affected by state mandates and the member’s specific benefit plan. Any applicable federal regulatory requirements, the member’s benefit design, or other utilization management programs may alter coverage or approval determinations.

Approvals may be conditionally denied when required supporting information is missing. UnitedHealthcare may rely on previous claim/medication history, ICD-10 diagnosis codes, and claim logic for automated approval or re-approval; when those data are not present or do not support the request, the prior authorization may be denied. Ensure required documentation is provided to avoid denial by automated rules or clinical review.

Utilization and Claim Logic / Coding

Utilization/claim logicmixed

ICD-10

diagnosis codes may be used for automated approval/re-approval processes

Provider Requirements and Actions

Prior Authorization

Provider Requirements and Actions

Prior Authorization Required. Initial authorization requires documentation of diagnosis, genotype, age, and Trikafta history or exception; reauthorization requires documentation of clinical response. Missing or incomplete documentation may lead to denial or manual review.

Initial authorization: diagnosis of cystic fibrosis, lab results showing ≥1 responsive CFTR mutation (or FDA‑cleared test if genotype unknown), patient ≥6 years of age, and either trial/failure/contraindication/intolerance to Trikafta OR mutation responsive to Alyftrek but not Trikafta, or current Alyftrek use documented by claims/medical records.
Reauthorization: documentation of positive clinical response to Alyftrek (e.g., improved or stable lung function). Authorization issued for 12 months; state mandates and member plan benefits may affect coverage.
Current therapy documentation: claims history or medical records must document date and duration of therapy. Patients established on therapy via manufacturer samples or assistance programs must meet initial authorization criteria as if new, unless claims documentation demonstrates ongoing therapy.
Trikafta-related criteria / Step therapy: a history of trial and failure, contraindication, or intolerance to Trikafta is required unless the patient has a mutation responsive to Alyftrek but not Trikafta or is a documented current user of Alyftrek.
Automated approval and claim-history reliance: UnitedHealthcare may approve initial and reauthorization requests based solely on prior claim/medication history, diagnosis codes (ICD-10), and/or claim logic; use of automated processes varies by program and therapeutic class. Missing claim history or documentation may trigger manual review or denial.

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 other responsive CFTR mutation. Its mechanism targets the CFTR protein to improve chloride transport in patients with responsive mutations. UnitedHealthcare’s criteria require laboratory documentation of a responsive CFTR mutation or other evidence of responsiveness as described in the Alyftrek prescribing information.

Definitions and Key Terms

Responsive CFTR mutation — definition and relation to prescribing information

DefinitionA CFTR gene mutation listed in the Alyftrek Prescribing Information as responsive based on clinical data, in vitro data, or extrapolated data.

Source for responsive mutationsComplete, up-to-date list of responsive CFTR mutations is referenced in the Alyftrek Prescribing Information (see policy references).

Assay notesSome mutations (e.g., N1303K) are predicted responsive only by HBE assay; other in‑vitro predictions are supported by FRT assay; efficacy is extrapolated for certain non-canonical splice mutations.

Genotype unknownIf the patient’s genotype is unknown, an FDA‑cleared CF mutation test should be used to confirm presence of at least one indicated mutation.

Relation to age criterionResponsive mutation requirement applies for patients aged ≥6 years who are eligible for Alyftrek therapy.