ModifiedCignaPolicy N/A

Trikafta (elexacaftor/tezacaftor/ivacaftor) prior authorization

Policy governs prior authorization and medical necessity criteria for Trikafta for treatment of cystic fibrosis in Cigna-administered health benefit plans, including age and genotype requirements and prescriber specialty requirements.

Policy Summary

PayerCigna

PolicyTrikafta (elexacaftor/tezacaftor/ivacaftor) prior authorization

Policy CodePolicy N/A

Change TypeMaterial update — criteria and indications revised

Effective DateN/A

Next Review DateN/A

Key ActionObtain prior authorization and document age ≥2 years, a qualifying CFTR mutation from the FDA-approved list, required evidence (newborn screen, family history, or clinical presentation) and demonstration of abnormal CFTR function.

SourceLink

POLICY UPDATE CHANGES

Trikafta oral granules were added to the policy.

Age criterion changed to ≥ 2 years based on the new indication for Trikafta.

Requirement that CFTR mutation be pathogenic or likely pathogenic was modified and 94 additional gene mutations were added to the list.

Clarified diagnostic requirements: at least one of newborn screen, family history, or clinical presentation, and evidence of abnormal CFTR function by sweat chloride, two CF-causing mutations, or abnormal nasal potential difference.

Conditions not covered updated to include patients with unknown CFTR gene mutation, combination therapy with other CFTR modulators, and infertility.

≥2minimum age (years)

1 yrinitial approval

94mutations added

Coverage Criteria for Trikafta

Initial coverage — FDA-approved indication

Covered when ALL of the following are met

FDA-Approved Indication: 1. Cystic Fibrosis. Approve for 1 year if the patient meets ALL of the following (A, B, C, D, and E):

From policy statement

A: Age: Patient is ≥ 2 years of age≥ 2 years

chunk 16

B: Genotype: Patient has at least ONE pathogenic or likely pathogenic CFTR variant from the list of responsive mutations in Table 1membership in Table 1

chunks 17-19

Initial therapy coverage criteria

Covered when ALL of the following are met:

Overall requirements

C: Evidence of CF via screening/history/clinical: 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, bronchiectasis, sinusitis, failure to thrive, pancreatic insufficiency (chunk 20)
D: Evidence of abnormal CFTR function: i. Elevated sweat chloride test; OR ii. Two cystic fibrosis-causing CFTR mutations; OR iii. Abnormal nasal potential difference
chunk 20
E and other requirements: Patient has at least one CFTR mutation included in the FDA-approved list and meets age criterion (≥ 2 years). Medication prescribed by or in consultation with a pulmonologist or CF specialist.
Mutation lists in chunks 17-19; age and prescriber requirement in chunk 16 and 20

Claims submitted without covered diagnosis and/or procedure codes under the applicable coverage policy will be denied as not covered. Providers must submit services with the most appropriate covered codes in effect on the date of service; reimbursement is not allowed for services billed for conditions or diagnoses that are not covered under this policy.

Use of Trikafta for any purpose outside the FDA‑approved indication is considered not medically necessary. This includes use in patients with an unknown CFTR gene mutation, use as combination therapy with other CFTR modulators, and use for infertility. A patient with cystic fibrosis should be evaluated against the FDA‑approved indication criteria in this policy before coverage is approved.

Trikafta is not medically necessary for patients whose CFTR mutation status is unknown, for concurrent administration with other CFTR modulators (for example, ivacaftor‑containing or tezacaftor‑containing products), and for treatment of infertility. An FDA‑cleared CFTR mutation test should detect at least one indicated mutation prior to Trikafta use.

Coding and Diagnostic Criteria

Productmixed

N/A	Product: Trikafta (elexacaftor/tezacaftor/ivacaftor) — tablets and oral granules, co-packaged

FDA-Approved CFTR Mutations (enumerated)mixed

G194R	G194R
I807M	I807M
Q237H	Q237H
R1070Q	R1070Q
V1240G	V1240G
D924N	D924N
G194V	G194V
I980K	I980K
Q359R	Q359R
R1070W	R1070W

1–10 of 163

1/17

inv-08: Sweat chloride — diagnostic thresholds

Sweat chloride ≥ 60 mmol/LEstablishes a diagnosis of cystic fibrosis (CF)

Sweat chloride < 30 mmol/LCF is unlikely (rare exceptions require genetic/physiologic confirmation)

Sweat chloride 30–59 mmol/LIndeterminate — proceed with CFTR genetic analysis and, if needed, physiologic testing (NPD or ICM)

inv-09: Minimum age — >= 2 years

Minimum approved age>= 2 years

Prescribing noteMedication must be prescribed by or in consultation with a pulmonologist or CF specialist

Provider Requirements and Authorization Guidance

Prior Authorization

Prior authorization required

Prior Authorization is recommended for prescription benefit coverage of Trikafta. Approval requires Trikafta to be prescribed by or in consultation with a physician who specializes in the condition being treated (e.g., a pulmonologist or cystic fibrosis specialist). Approvals are provided for the duration noted in the policy.

Prior authorization recommended; approvals provided for 1 year when criteria met
Prescriber requirement: Must be prescribed by or in consultation with a pulmonologist or physician who specializes in cystic fibrosis

Denial Risk

Concurrent CFTR modulators

Trikafta must not be used in combination with other CFTR modulators. Claims or requests for concurrent use of Trikafta with other CFTR modulators (for example, Alyftrek™, Kalydeco®, Orkambi®, Symdeko®) are considered not medically necessary and will be denied.

Background

Trikafta is a cystic fibrosis transmembrane conductance regulator (CFTR) modulator that combines elexacaftor, tezacaftor, and ivacaftor. It is indicated for treatment of cystic fibrosis in patients ≥ 2 years of age who have at least one F508del mutation or another CFTR mutation responsive to Trikafta based on clinical or in‑vitro data.

Definitions and Diagnostic Criteria

inv-19: CF diagnosis

Diagnostic requirements (summary)Diagnosis requires a compatible clinical presentation PLUS evidence of CFTR dysfunction (sweat chloride, genetic, or physiologic testing)

Sweat chloride criterionSweat chloride ≥ 60 mmol/L alone establishes CF diagnosis

Alternative evidenceTwo CF-causing CFTR mutations OR abnormal nasal potential difference (NPD) can demonstrate CFTR dysfunction

Testing sequence guidanceConsider sweat chloride first, then CFTR genetic analysis, then physiologic testing (NPD or ICM); all individuals diagnosed with CF should have sweat chloride and genetic testing

inv-20: Clinical presentation consistent with cystic fibrosis

Example: neonatal presentation