Cystic Fibrosis

POLICY NUMBER

L.5.01.417

Alyftrek (vanzacaftor/tezacaftor/deutivacaftor tablets)

Kalydeco (ivacaftor)

Orkambi (lumacaftor/ivacaftor)

Symdeko (tezacaftor/ivacaftor

kit

)

Trikafta (elexacaftor/tezacaftor/ivacaftor

kit

)

Please perform a formulary drug search on your patient’s member ID to ensure the prescription drug is covered under their benefit plan. The medication(s) in this medical policy may not be covered under a specific member’s benefit plan.

DESCRIPTION

Cystic fibrosis (CF) is an autosomal recessive disease caused by pathogenic mutations of the CFTR (CF transmembrane conductance regulator) protein. The CFTR protein is a complex chloride channel and regulatory protein found in all exocrine tissues. Defects in the CFTR protein cause deranged transport of chloride and other CFTR-affected ions (e.g., sodium and bicarbonate) resulting in thick, viscous secretions in the lungs, pancreas, liver, intestine, and reproductive tract and increased salt content in sweat gland secretions.

Treatment of CF requires a multidisciplinary approach and may include antibiotics, bronchodilators, airway clearance therapies, anti-inflammatory agents, nutritional support, and CFTR modulators. CFTR modulators improve production, intracellular processing, and/or function of the CFTR protein. A CFTR modulator is recommended for all CF patients who are eligible based on age and genotype.

Alyftrek (vanzacaftor, tezacaftor, and deutivacaftor) is indicated for the treatment of CF in patients aged 6 years and older who have at least one F508del mutation or another responsive mutation in the CFTR gene.

Kalydeco (ivacaftor) is indicated for the treatment of CF in patients 1 month and older who have at least one mutation in CFTR gene that is responsive to ivacaftor potentiation based on clinical and/or in vitro assay data.

Orkambi (lumacaftor and ivacaftor) is indicated for the treatment of CF in patients aged 1 year and older who are homozygous for the F508del mutation in the CFTR gene.

Symdeko (tezacaftor and ivacaftor kit) is indicated for the treatment of CF in patients aged 6 years and older who are homozygous for the F508del mutation or who have at least one mutation in the CFTR gene that is responsive to tezacaftor/ivacaftor based on in vitro data and/or clinical evidence.

Trikafta (elexacaftor, tezacaftor, and ivacaftor kit) is indicated for the treatment of CF in patients aged 2 years and older who have at least one F508del mutation in the CFTR gene or a mutation in the CFTR gene that is responsive based on clinical and/or in vitro data.

POLICY

Prior authorization is required.

The use of samples by an individual will not be considered current or stable therapy to satisfy Medical Policy requirements.

Initial Criteria

The requested agent may be considered medically necessary when ALL of the following criteria are met:

1. ONE of the following:

   1. The request is for Kalydeco (ivacaftor) and t

      he individual is ≥1 month of age;

   2. The request is for Orkambi (lumacaftor/ivacaftor) and the individual is ≥1 year of age;

   3. The request is for Symdeko (tezacaftor/ivacaftor kit) and the individual is ≥6 years of age;OR

   4. The request is for Trikafta (elexacaftor/tezacaftor/ivacaftor kit) and the individual is ≥2 years of age;

2. ALL of the following:

   1. The individual has a documented diagnosis of cystic fibrosis (CF);

   2. The individual has a CFTR gene mutation(s), confirmed by genetic testing, according to the FDA label for the requested agent (medical records required); AND

   3. If the requested agent is Kalydeco, the individual does NOT have F508del mutation on BOTH alleles of CFTR gene (NOT homozygous);

3. The requested agent will not be used in combination with another CFTR modulator agent;

4. The prescriber is a specialist in the area of the individual’s diagnosis (e.g., physician who specializes in the treatment of cystic fibrosis, pulmonologist) or has consulted with a specialist in the area of the individual’s diagnosis;

5. The prescribed dosage is within the program quantity limits based on FDA approved labeled dosage; AND

6. The individual does NOT have any FDA labeled contraindications to the requested agent.

Length of Approval:12 months

Renewal EvaluationThe requested agent may be approved for RENEWAL when ALL of the following criteria are met:

1. The individual has been previously approved for the requested agent through the BCBSMS PA process;

2. The individual has documented clinical improvement from baseline [e.g., improvement in FEV1, increase in weight/BMI, improvement in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain score, improvements in respiratory symptoms (cough, sputum production, and difficulty breathing), and/or reduced number of pulmonary exacerbations];

3. The individual will NOT be using the requested agent in combination with another CFTR modulator agent;

4. The prescriber is a specialist in the area of the individual’s diagnosis (e.g., physician who specializes in the treatment of cystic fibrosis, pulmonologist) or has consulted with a specialist in the area of the individual’s diagnosis;

5. The prescribed dosage is within the program quantity limits based on FDA approved labeled dosage; AND

6. The individual does NOT have any FDA labeled contraindications to the requested agent.

Length of Approval: 12 months

Alyftrek (vanzacaftor, tezacaftor, and deutivacaftor) is considered not medically necessary as there are other options covered by the Plan for the treatment of cystic fibrosis.

Services related to delivery and/or administration of a medication which have not been approved through the BCBSMS PA review process will be considered not medically necessary.

POLICY EXCEPTIONS

State Health Plan (State and School Employees): The prescription drug(s) in this medical policy may be covered under a prescription drug benefit plan administered by the State Health Plan’s Pharmacy Benefit Manager. Please perform a formulary drug search at https://www.dfa.ms.gov/cvs-caremark and submit any required Prior Authorization Requests for coverage determination to the Plan’s Pharmacy Benefit Manager. Services related to delivery and/or administration of a medication determined to be not medically necessary will also be considered not medically necessary. Services related to delivery and/or administration of a self-administered drug are not covered.

POLICY GUIDELINES

The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.

Medically Necessary is defined as those services, treatments, procedures, equipment, drugs, devices, items or supplies furnished by a covered Provider that are required to identify or treat a Member's illness, injury or Mental Health Disorders, and which Company determines are covered under this Benefit Plan based on the criteria as follows in A through D:

A.  consistent with the symptoms or diagnosis and treatment of the Member's condition, illness, or injury; and

B.  appropriate with regard to standards of good medical practice; and

C.  not solely for the convenience of the Member, his or her Provider; and

D.  the most appropriate supply or level of care which can safely be provided to Member. When applied to the care of an Inpatient, it further means that services for the Member's medical symptoms or conditions require that the services cannot be safely provided to the Member as an Outpatient.

For the definition of medical necessity, “standards of good medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. BCBSMS makes no payment for services, treatments, procedures, equipment, drugs, devices, items or supplies which are not documented to be Medically Necessary. The fact that a Physician or other Provider has prescribed, ordered, recommended, or approved a service or supply does not in itself, make it Medically Necessary. 

BCBSMS may request medical records for determination of medical necessity. When medical records are requested, letters of support and/or explanation are often useful, but are not sufficient documentation unless all specific information needed to make a medical necessity determination is included.

POLICY HISTORY

12/04/2015: New policy added. This policy replaces the Kalydeco® (ivacaftor) medical policy. Effective 12/04/15.

05/26/2016: Policy number L.5.01.417 added.

10/19/2016: Policy revised to change indication for patients using Orkambi from "12 years and older" to "6 years and older."

11/01/2016: Approved by Pharmacy & Therapeutics (P&T) Committee.

06/01/2017: Policy description and policy section revised to update mutations indicated for Kalydeco.

09/01/2017: Policy description and policy section updated to add mutations indicated for Kalydeco.

11/14/2017: Policy reviewed and approved by Pharmacy & Therapeutics (P&T) Committee.

11/01/2018: Policy reviewed and approved by Pharmacy & Therapeutics (P&T) Committee. Policy revised to update indications and dosage information for Kalydeco and Orkambi. Added indications for Symdeko. For Kalydeco, patient age changed from "2 years" to "12 months." For Orkambi, patient age changed from "6 years" to "2 years." Policy statement for reauthorization updated to state that continuation of Kalydeco, Orkambi, or Symdeko can be considered medically necessary upon meeting certain criteria. Sources updated.

10/01/2019: Policy reviewed and approved by Pharmacy & Therapeutics (P&T) Committee. Policy description revised to remove FDA approved indications. Policy statements updated to add generic drug names. Policy statement criteria for Orkambi revised to state: "Submission of laboratory results from an FDA-cleared CF mutation test confirming the patient is homozygous for the F508del mutation in the CFTR gene." Added statement that Symdeko (tezacaftor/ivacaftor and ivacaftor co-packaged) may be considered medically necessary when ALL of the listed criteria are met. Sources updated.

12/16/2019: Policy updated to add indications for Trikafta. Sources updated. Code Reference section updated to add ICD-10 diagnosis codes E84.0 - E84.9.

02/18/2021: Policy reviewed and approved by Pharmacy & Therapeutics (P&T) Committee. Policy description updated. Policy section updated to revise policy statement criteria for Kalydeco, Orkambi, Symdeko, and Trikafta. Renewal evaluation criteria revised. Added statement that services related to delivery and/or administration of a medication which have not been approved through the BCBSMS PA review process will be considered not medically necessary. Policy Guidelines updated regarding BCBSMS request for medical records. Sources updated.

07/13/2021: Policy reviewed and approved by Pharmacy & Therapeutics (P&T) Committee. Tables regarding genes updated for Kalydeco and Symdeko. For Trikafta, the member age requirement changed from "12" to "6" and a table was added to list genes. Policy Guidelines updated to remove definition of investigative. Sources updated.

02/01/2023: Policy Exceptions updated to add the following: State Health Plan (State and School Employees): The prescription drug(s) in this medical policy may be covered under a prescription drug benefit plan administered by the State Health Plan’s Pharmacy Benefit Manager. Please perform a formulary drug search at https://www.dfa.ms.gov/cvs-caremark and submit any required Prior Authorization Requests for coverage determination to the Plan’s Pharmacy Benefit Manager. Services related to delivery and/or administration of a medication determined to be not medically necessary will also be considered not medically necessary. Services related to delivery and/or administration of a self-administered drug are not covered.

07/01/2025: Effective 09/01/2025 - Policy reviewed and approved by the Pharmacy & Therapeutics (P&T) Committee. Policy updated to change "Symdeko (tezacaftor/ivacaftor and ivacaftor co-packaged)" to "Symdeko (tezacaftor/ivacaftor kit)" and "Trikafta (elexacaftor/tezacaftor/ivacaftor and ivacaftor co-packaged)" to "Trikafta (elexacaftor/tezacaftor/ivacaftor kit)." Policy description updated regarding cystic fibrosis and indications for Kalydeco (ivacaftor), Orkambi (lumacaftor and ivacaftor), Symdeko (tezacaftor and ivacaftor kit), and Trikafta (elexacaftor, tezacaftor, and ivacaftor kit). Policy statement revised to state that the use of samples by an individual will not be considered current or stable therapy to satisfy Medical Policy requirements. Policy section revised to remove CFTR gene mutation tables for Kalydeco, Symdeko, and Trikafta. Revised age criteria for Kalydeco, Orkambi, and Trikafta. Initial criteria revised regarding confirmed CFTR gene mutation(s), combination therapy, prescriber requirement, dose requirements, and FDA labeled contraindications. Renewal criteria revised regarding documented clinical improvement, combination therapy, prescriber requirement, dose requirements, and FDA labeled contraindications. Sources updated. Policy update effective 09/01/2025.

09/01/2025: Policy description updated regarding indications for Alyftrek (vanzacaftor, tezacaftor, and deutivacaftor). Added policy statement that Alyftrek (vanzacaftor, tezacaftor, and deutivacaftor) is considered not medically necessary as there are other options covered by the Plan for the treatment of cystic fibrosis. Sources updated.

SOURCE(S)

1. Alyftrek prescribing information. Vertex Pharmaceuticals Incorporated. January 2025. Last accessed July 2025.

2. Kalydeco prescribing information. Vertex Pharmaceuticals Incorporated. June 2024. Last accessed March 2025.

3. Katkin JP. Cystic fibrosis: Clinical manifestations and diagnosis. In: UpToDate, Connor RF (Ed), Wolters Kluwer. https://www.uptodate.com/contents/cystic-fibrosis-clinical-manifestations-and-diagnosis (Accessed on March 12, 2025)

4. Orkambi prescribing information. Vertex Pharmaceuticals Incorporated. December 2024. Last accessed March 2025.

5. Ren CL, Morgan RL, Oermann C, et al. Cystic Fibrosis Foundation Pulmonary Guidelines. Use of Cystic Fibrosis Transmembrane Conductance Regulator Modulator Therapy in Patients with Cystic Fibrosis. Ann Am Thorac Soc 2018; 15:271.

6. Simon RH. Cystic fibrosis: Treatment with CFTR modulators. In: UpToDate, Connor RF (Ed), Wolters Kluwer. https://www.uptodate.com/contents/cystic-fibrosis-treatment-with-cftr-modulators (Accessed on March 12, 2025)

7. Symdeko prescribing information. Vertex Pharmaceuticals Incorporated. February 2025. Last accessed July 2025.

8. Trikafta prescribing information. Vertex Pharmaceuticals Incorporated. February 2025. Last accessed July 2025.

CODE REFERENCE

This may not be a comprehensive list of procedure codes applicable to this policy.

The code(s) listed below are ONLY medically necessary if the procedure is performed according to the "Policy" section of this document.

Covered Codes

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