ModifiedmhnPolicy CP.PHAR.440

Elexacaftor/Ivacaftor/Tezacaftor; Ivacaftor (Trikafta)

Defines medical necessity criteria, dosing, and authorization rules for Trikafta in members with cystic fibrosis across commercial, HIM, and Medicaid lines of business; affects prescribers and prior authorization reviewers.

Policy Summary

Payermhn

PolicyElexacaftor/Ivacaftor/Tezacaftor; Ivacaftor (Trikafta)

Policy CodePolicy CP.PHAR.440

Change TypeCriteria revisedpediatric expansionexclusions updated

Effective DateDec 1, 2019

Next Review Date

Key ActionSubmit prior authorization with documentation of required pulmonary function testing and genotype evidence to meet initial criteria.

SourceLink

POLICY UPDATE CHANGES

Pediatric expansion and new granule formulation were added to the criteria and dosing.

Initial and continuation therapy criteria were revised to change ppFEV1 and LCI documentation and to allow stabilization or improvement language.

Legacy Wellcare requirements were modified including shorter initial approval duration and relaxation of sweat chloride and in vitro testing requirements.

Continued therapy response definitions clarified: LCI improvement defined as decrease from baseline and ppFEV1 improvement defined as increase from baseline.

Initial approval duration was changed from 12 months to 6 months to align with standard Medicaid initial approval duration.

Pediatric expansion and new granule formulation added; pulmonary function test documentation requirements updated to specify age-based ppFEV1 and LCI options and continuation criteria adjusted to include stabilization/decrease in LCI.

Removed lung clearance index (LCI) from criteria and updated initial approval duration from 4 months to 6 months; added indication for some non-F508del mutations responsive to Trikafta.

Alyftrek added to list of CFTR modulator concurrent exclusion criteria.

Continued therapy criteria language clarified to define positive response as improvement (e.g., decrease) in LCI and increase in ppFEV1 from baseline.

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Age ≥ 2minimum FDA-indicated age for Trikafta

6 monthsinitial authorization length

12 monthscontinuation authorization length

ppFEV1 ≥ age 6baseline spirometry requirement

Sweat Cl ≥ 60diagnostic threshold

Alyftrekconcurrent exclusion added

Coverage Criteria for Trikafta

Initial Therapy

Covered when ALL of the following are met:

Diagnosis of cystic fibrosis: Diagnosis of CF confirmed by all of the following: (a) clinical symptoms consistent with CF in at least one organ system, or positive newborn screen or genetic testing for siblings of patients with CF; (b) evidence of CFTR dysfunction as either i. sweat chloride ≥ 60 mmol/L OR ii. genetic testing confirming two disease‑causing CFTR mutations (one from each parental allele); and (c) confirmation of either i. at least one F508del mutation OR ii. a CFTR mutation responsive to Trikafta based on clinical and/or in vitro data (see Appendix E).Sweat chloride ≥ 60 mmol/L

See Appendix E for responsive mutations

Age ≥ 2 years.

Prescriber: Prescribed by or in consultation with a pulmonologist.

Baseline pulmonary function (age ≥ 6 years): For members age ≥ 6 years: documentation of baseline percent predicted FEV1 (ppFEV1) performed within the last 90 days.ppFEV1 within 90 days

Chart notes, lab results, or test reports must be submitted

Concurrent CFTR modulator exclusion: Trikafta is not prescribed concurrently with other CFTR modulators (for example: Alyftrek, Orkambi, Kalydeco, Symdeko).

Verify prior or concurrent CFTR modulator therapy

Dose limits and formulation: Requested dose does not exceed specified age‑ and weight‑based regimens and corresponds to approved tablet or oral granule formulations (see dosing table for ages 2+ and weight categories).

Initial approval duration: 6 months

Initial Therapy (summary)

Covered when ALL of the following are met (summary from revisions visible in this document):

High-level initial therapy summary: Member has a CFTR mutation responsive to Trikafta (per Appendix E or clinical/in vitro data) AND documentation of an age‑appropriate pulmonary function test (ppFEV1 for applicable ages; LCI was previously allowed as an alternative for younger children in prior revisions) as required by initial criteria AND dosing corresponds to age/weight/formulation per product availability.See mutation list and dosing tables

Pediatric expansion and granule formulation included; LCI previously allowed as an alternative for certain ages

Initial Therapy — Coverage is provided when updated clinical criteria are met, including genotype responsiveness and documented pulmonary function improvem...

Coverage is provided when updated clinical criteria are met, including genotype responsiveness and documented pulmonary function improvement or stabilization as specified.

Updated initial approval requirements: Member meets the revised initial criteria: responsive genotype (F508del or other Trikafta‑responsive mutation per Appendix E), age‑appropriate pulmonary function documentation, prescriber specialty, and dosing consistent with age/weight/formulation. Initial approvals are generally issued for 6 months.Initial approval duration = 6 months

RT4 revisions added pediatric expansion and granule formulation; LCI was later removed from criteria

Continued Therapy

Covered when ALL of the following are met:

Continuation eligibility: Member currently receiving medication via Centene benefit and/or previously met initial approval criteria, or member is receiving medication and is covered under applicable continuity of care regulations.

Follow state‑specific addendums for continuity of care when applicable

Clinical response by age group: For age < 6 years: member is responding positively to therapy (examples: decreased pulmonary exacerbations, increased BMI, improved respiratory symptoms). For age ≥ 6 years: member is responding as evidenced by stabilization or improvement (increase) in ppFEV1 from baseline.Documented in chart/test results

3Q2024 clarified improvement directions for ppFEV1 and LCI

Concurrent CFTR modulator exclusion continues: Trikafta is not prescribed concurrently with other CFTR modulators (e.g., Alyftrek, Orkambi, Kalydeco, Symdeko).

Concurrent exclusion applies to continuation requests

Continuation Therapy (summary)

Continued therapy is covered when ALL of the following are met:

High-level continuation summary: Documentation shows stabilization or improvement in ppFEV1 from baseline, or stabilization or decrease in LCI from baseline where applicable; member remains on appropriate dosing regimen consistent with age/weight.Improvement defined as increase (ppFEV1) or decrease (LCI) from baseline

Policy revisions clarified 'stabilization or improvement' and defined direction of change for ppFEV1 and LCI

Continuation Therapy — Covered when ANY of the following demonstrate response from baseline (as clarified):

Covered when ANY of the following demonstrate response from baseline (as clarified):

Clinical response criteria for continuation: Stabilization or improvement in ppFEV1 (documented increase from baseline) OR stabilization or decrease in LCI from baseline where applicable (note: LCI was later removed from criteria).Documented in chart/test results

3Q2024 clarified improvement definitions; LCI removal later (2025)

Concurrent Therapy Exclusions

Not covered or excluded when concurrent excluded agents are used:

Concurrent exclusion: Use of Trikafta concurrent with Alyftrek or other CFTR modulators listed on the concurrent exclusion list is not permitted.N/A

Alyftrek was added to the concurrent exclusion list in 3Q2025

Non‑FDA approved indications that are not specifically addressed in this policy are not authorized unless the provider submits sufficient documentation of efficacy and safety according to the applicable off‑label use policies: CP.CPA.09 (Commercial), HIM.PA.154 (Health Insurance Marketplace), or CP.PMN.53 (Medicaid).

Legacy Wellcare‑specific requirements for prior in vitro testing and for demonstrating lack of responsiveness to other CFTR modulators were removed in prior revisions. The document fragment does not list additional explicit exclusions tied to those legacy requirements.

Concurrent prescribing of Trikafta with other CFTR modulators on the policy's exclusion list is not permitted. The concurrent exclusion list was updated to include Alyftrek; verify that the member is not receiving an excluded CFTR modulator prior to approval.

Uses of Trikafta for non‑FDA approved indications without sufficient supporting documentation of efficacy and safety per the referenced off‑label use policies are considered not authorized and may be denied.

Prior restrictive requirements (for example, legacy in vitro baseline chloride transport thresholds) are not explicitly retained in this fragment. Historical edits show those prior thresholds and related step‑therapy requirements were removed during earlier revisions.

Requests for Trikafta that do not meet the policy's genotype requirements, lack the required age‑appropriate pulmonary function documentation, or conflict with concurrent‑therapy exclusion rules (for example, concurrent use with Alyftrek) are subject to denial as not medically necessary.

Coding and Clinical Thresholds

Affected Codes (placeholder)mixed

affected codes

Policy references updated to affect prior authorization and approval duration codes (exact billing codes not listed in this excerpt).

inv-15: Sweat chloride — diagnostic threshold for CFTR dysfunction

Diagnostic sweat chloride thresholdSweat chloride ≥ 60 mmol/L confirms CFTR dysfunction for diagnostic criteria

Supporting guidance sourceCystic Fibrosis Foundation guidance referenced in policy endorses elevated sweat chloride ≥ 60 mmol/L for CFTR dysfunction confirmation

Policy locationListed under 'Diagnosis of CF' as evidence of CFTR dysfunction (see Appendix D)

inv-16: Baseline ppFEV1 — Per policy, performed within last 90 days for age ≥ 6 years

Required testBaseline percent predicted FEV1 (ppFEV1) required for members age ≥ 6 years

TimingBaseline ppFEV1 must have been performed within the last 90 days

Provider Actions and Prior Authorization Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required. Provider must submit documentation (such as office/chart notes, pulmonary function test results, genetic testing, and other clinical information) supporting that the member meets all initial or continuation criteria. Requests that lack required supporting documentation may be denied.

Prior authorization required for initial and continuation therapy
Approval duration for initial authorization: generally 6 months (Medicaid-consistent)

Documentation Required

Mutation and Diagnosis Documentation Required

Documentation must include evidence of cystic fibrosis diagnosis and CFTR dysfunction (e.g., clinical symptoms, positive newborn screen, genetic testing, or elevated sweat chloride) and genotype information showing a Trikafta-responsive mutation per Appendix E/Prescriber information. Provider must supply genetic test results or mutation documentation with the PA request.

Background

Trikafta (elexacaftor/tezacaftor/ivacaftor) is a triple‑combination CFTR modulator that increases CFTR protein processing, trafficking, and channel gating to improve CFTR function in patients with certain CFTR mutations, including F508del. It is indicated for patients aged 2 years and older with at least one F508del mutation or another CFTR mutation shown to be responsive by clinical or in vitro data. Coverage under this policy requires documentation of diagnosis, genotype responsiveness, appropriate prescriber specialty, and age‑appropriate pulmonary function testing per the criteria.

Definitions and Abbreviations

inv-32: cystic fibrosis transmembrane conductance regulator — CFTR

AcronymCFTR = cystic fibrosis transmembrane conductance regulator

Functional roleProtein involved in chloride transport; target of elexacaftor/tezacaftor/ivacaftor therapy

Policy relevanceCFTR dysfunction (e.g., via sweat chloride or genetic testing) is required for diagnosis in policy criteria

inv-33: percent predicted forced expiratory volume in 1 second — ppFEV1

DefinitionppFEV1 = percent predicted forced expiratory volume in 1 second

Clinical noteMost children can perform spirometry by age 6; used as age-based pulmonary function metric in policy

Policy Summary

Payermhn

PolicyElexacaftor/Ivacaftor/Tezacaftor; Ivacaftor (Trikafta)

Policy CodePolicy CP.PHAR.440

Change TypeCriteria revisedpediatric expansionexclusions updated

Effective DateDec 1, 2019

Next Review Date

Key ActionSubmit prior authorization with documentation of required pulmonary function testing and genotype evidence to meet initial criteria.

SourceLink

On This Page

Dose limits for continuation: If request is for a dose increase, the new dose must not exceed the specified age/weight regimens (same table as initial therapy).

Approval duration for continuation: 12 months

Policy placementSpecified in Initial Therapy criteria as age-based pulmonary function requirement

inv-17: LCI threshold alternative for young children — LCI ≥ 7.4 as an alternative option for ppFEV1 for age <6 years (per prior revision history)

LCI alternative thresholdLCI ≥ 7.4 was allowed as an alternative pulmonary function option for age < 6 years in prior revisions

Revision contextRT4 (05.04.23 / 06.23) added alternative option permitting LCI ≥ 7.4 for age <6 years

Later document changesNote: LCI was subsequently removed from criteria in 2025 revisions

inv-18: Initial approval duration — 6 months

Initial approval durationInitial approvals are issued for 6 months

Rationale / alignmentInitial duration revised from 12 months to 6 months to align with standard Medicaid initial approval practices

Continuation contrastContinued therapy approvals are generally issued for 12 months per continuation criteria

Provide genetic testing or documentation of CFTR mutation responsive to elexacaftor/tezacaftor/ivacaftor
Include evidence of CFTR dysfunction (e.g., sweat chloride ≥ 60 mmol/L when applicable)

Documentation Required

Pulmonary Function Test Documentation Required

Provide documentation of one of the specified pulmonary function tests with the prior authorization request. For ages > 2 years, include percent predicted FEV1 (ppFEV1) results. (Policy revisions have removed LCI in some updates; confirm age- and policy-specific acceptable tests.) Lack of required pulmonary function documentation is a common reason for denial.

ppFEV1 result for age > 2 years (include date and values)
If applicable per current policy, only approved alternatives may be accepted — verify current Appendix and criteria

Denial Risk

Concurrent CFTR Modulators Excluded

Trikafta must not be prescribed concurrently with other CFTR modulators. Concurrent use with agents such as Orkambi, Kalydeco, Symdeko, and newly added Alyftrek is excluded and will result in denial if used concurrently.

Concurrent CFTR modulators excluded: Orkambi, Kalydeco, Symdeko, Alyftrek (as of 3Q2025 update)

Step Therapy

Step Therapy / Prior-Modulator Requirements Revised

Step-therapy / prior-modulator requirements have been revised: the policy removed prior requirements demonstrating lack of responsiveness to other CFTR modulators and removed several in vitro baseline chloride transport testing requirements. Do not submit prior-modulator failure evidence unless specifically requested by plan; follow the current criteria for genotype and clinical severity instead.

Prior requirement to demonstrate lack of response to other CFTR modulators has been removed
In vitro baseline chloride transport testing requirement removed

Denial Risk

Denial Triggers and Risks

Denials may be issued for: requests for non-FDA indications without sufficient off-label documentation per applicable off-label policies; missing or inadequate supporting documentation (chart notes, labs, PFTs, genetic testing); concurrent use of excluded CFTR modulators; or failure to meet revised clinical criteria (age-appropriate pulmonary function documentation, genotype responsive to Trikafta, or continuity/response requirements for continuation).

Non-FDA indications require off-label policy documentation (CP.CPA.09, HIM.PA.154, CP.PMN.53 as applicable)
Incomplete/missing pulmonary function or genotype documentation may trigger denial
Concurrent excluded CFTR modulator use will result in denial

Policy useBaseline and continued therapy response assessments reference ppFEV1 per age-specific criteria

inv-34: Responsive mutation (in vitro/extrapolated) — Mutations labeled responsive are supported by in vitro assays (FRT or HBE) or by extrapolation from clinical trials when direct clinical ...

DefinitionResponsive mutation (in vitro/extrapolated) = CFTR mutations labeled responsive based on in vitro assays (FRT or HBE) or extrapolation from clinical trial data when direct trials are infeasible

Supporting detailAppendix E lists mutations with response evidence from Trials 1,2,5 or predicted by FRT/HBE assays

Policy implicationPresence of a responsive mutation can satisfy genotype requirement for Trikafta coverage per policy

inv-35: LCI — Lung clearance index — previously used as an alternative pulmonary function test metric for younger children; later removed from criteria.

DefinitionLCI = Lung clearance index; previously used as an alternative pulmonary function metric for younger children

Policy historyRT4 revisions (2023) allowed LCI as an alternative for age <6 years; continued therapy language referenced stabilization/decrease in LCI from baseline

Current statusLCI was later removed from criteria in 2025 revisions and is no longer part of the active criteria

inv-36: Non-F508del responsive mutation — A CFTR gene mutation other than F508del that has clinical evidence of responsiveness to Trikafta and may be eligible under the updated in...

DefinitionNon-F508del responsive mutation = a CFTR mutation other than F508del with clinical evidence of responsiveness to Trikafta

Policy updateRT4 (01.16.25) added indications for some non-F508del mutations responsive to Trikafta based on clinical data and updated Appendix E

Coverage implicationPresence of a non-F508del responsive mutation may meet genotype requirement for initial approval per updated criteria