ModifiedCignaPolicy N/A

Cystic Fibrosis Transmembrane Conductance Regulator -Orkambi Prior - Authorization Policy

Policy Summary

PayerCigna

PolicyCystic Fibrosis Transmembrane Conductance Regulator -Orkambi Prior - Authorization Policy

Policy CodePolicy N/A

Change TypeCriteria revised and added

Effective Date

Next Review DateJul 9, 2025

Key ActionPrior authorization is required; document age, CFTR genotype showing two copies of F508del, supporting newborn screen/family history/clinical presentation, and evidence of abnormal CFTR function.

SourceLink

POLICY UPDATE CHANGES

Required that the patient has TWO copies of the F508del mutation (language standardized to 'TWO copies of the F508del mutation').

Added criterion requiring at least one of: positive newborn screen, family history of CF, or clinical presentation consistent with CF.

Added requirement for evidence of abnormal CFTR function as demonstrated by elevated sweat chloride, two CF-causing CFTR mutations, or abnormal nasal potential difference.

Conditions not covered updated to refer to the class of CFTR modulators rather than listing individual agents.

Infertility was added to Conditions Not Covered.

Policy title and verbiage updated to 'Cystic Fibrosis Transmembrane Conductance Regulator - Orkambi PA Policy' and 'conductance' added in relevant places.

Coverage Summary

Defines prior authorization and medical necessity criteria for coverage of Orkambi (lumacaftor/ivacaftor tablets and oral granules) for treatment of cystic fibrosis in patients ≥ 1 year of age who are homozygous for TWO copies of the F508del mutation in the CFTR gene; approvals are provided for 1 year when all criteria are met. Trikafta is generally preferred where indicated per guideline context.

Thresholds

Age≥ 1 year

Genotype copiesTWO copies of the F508del mutation

StatusMODIFIED

Coverage stancecovered_with_criteria

Initial Therapy Criteria (FDA-Approved Indication)

FDA-Approved Indication - Orkambi

Approve for 1 year if the patient meets ALL of the following (A, B, C, D, and E):

ALL of the following

Patient is ≥ 1 year of age
age at time of request
Patient has TWO copies of the F508del mutation in the cystic fibrosis transmembrane conductance regulator gene
homozygous for F508del (two copies)
Patient meets at least ONE of the following (i, ii, or iii):
- Positive cystic fibrosis newborn screening test
- Family history of cystic fibrosis
- Clinical presentation consistent with signs and symptoms of cystic fibrosis
  Examples include meconium ileus, sino-pulmonary symptoms (e.g., persistent cough, wheezing, obstructive PFTs, excess sputum), bronchiectasis, sinusitis, failure to thrive, pancreatic insufficiency

Prior Authorization

Prior authorization required

Prior authorization is required for Orkambi. Approvals are provided for one year when the policy criteria are met. Orkambi must be prescribed by or in consultation with a pulmonologist or a physician who specializes in the treatment of cystic fibrosis.

Approvals provided for 1 year when criteria are met

Documentation Required

Genotype and diagnostic documentation

Providers must document the patient’s age, confirm CFTR genotype showing TWO copies of the F508del mutation, document at least one of: positive newborn CF screening, family history of cystic fibrosis, or clinical presentation consistent with CF, and provide evidence of abnormal CFTR function.

Age ≥ 1 year
CFTR genotype showing TWO copies of the F508del mutation
At least ONE of: positive newborn screening; family history of CF; clinical presentation consistent with CF (e.g., meconium ileus, persistent cough, wheeze, bronchiectasis, sinusitis, failure to thrive, pancreatic insufficiency)
Evidence of abnormal CFTR function: at least ONE of elevated sweat chloride test; two CF-causing CFTR mutations; abnormal nasal potential difference

Conditions Not Covered (Not Medically Necessary)

Orkambi is considered not medically necessary for ANY other uses including, but not limited to, the following:

ANY of the following

Cystic Fibrosis, Heterozygous for the F508del Mutation in the CFTR gene (only one copy of F508del)
Combination therapy with other CFTR modulators (e.g., Kalydeco, Symdeko, Trikafta, Alyftrek) — Orkambi is not indicated in combination with other CFTR modulators containing ivacaftor
Combination includes agents containing ivacaftor; examples listed
Infertility

Applicable Codes

Drug / NDC (not specified)NDC

No codes listed

Provider Actions & Documentation Requirements

Note

Provider actions: prior authorization, required documentation, and denial conditions

Summary of actionable provider requirements and denial conditions for Orkambi.

Prior authorization is required; approvals provided for 1 year when criteria are met; medication must be prescribed by or in consultation with a pulmonologist or CF specialist. (prior_auth)
Documentation checklist: age (≥ 1 year); CFTR genotype showing TWO copies of F508del; at least ONE of newborn screen, family history of CF, or clinical presentation consistent with CF; evidence of abnormal CFTR function demonstrated by at least ONE of elevated sweat chloride, two CF-causing CFTR mutations, or abnormal nasal potential difference. (documentation)
Denial conditions: patients heterozygous for F508del (one copy), combination therapy with other CFTR modulators, and infertility are considered not medically necessary and will be denied. (denial_risk)

Clinical Evidence & References

Prescribing information: Orkambi tablets and oral granules; Vertex; December 2024.

Guideline: European Cystic Fibrosis Society Standards for CFTR variant-specific therapy (2023) and Standards for establishing and maintaining health (2024).

Note: Trikafta recommendation as preferred therapy where indications overlap is noted in the guideline background.

Background

Orkambi (lumacaftor/ivacaftor) is indicated for the treatment of cystic fibrosis in patients ≥ 1 year of age who are homozygous for the F508del mutation in the CFTR gene. If the patient's genotype is unknown, an FDA-cleared cystic fibrosis mutation test should be used to detect the presence of the F508del mutation on both alleles.

Clinical guidelines from the European Cystic Fibrosis Society (2023 Standards for CFTR variant-specific therapy and 2024 Standards for establishing and maintaining health) and the Cystic Fibrosis Foundation inform diagnostic approach and therapy selection; the Standards generally recommend Trikafta over other agents where indications overlap.

Per CF Foundation guidance, CF diagnosis requires both a compatible clinical presentation (for example, positive newborn screening, family history of CF, or signs/symptoms such as meconium ileus, sino-pulmonary symptoms, bronchiectasis, failure to thrive, pancreatic insufficiency) and evidence of abnormal CFTR function (e.g., elevated sweat chloride, two CF-causing CFTR mutations, or abnormal nasal potential difference).

Approvals require the medication to be prescribed by or in consultation with a pulmonologist or physician specializing in cystic fibrosis.

Definitions

TermF508del

DefinitionTWO copies denote homozygosity for the F508del CFTR variant

Revision History

04/10/2024revised

Reference to 'Phe508del' was removed and language standardized to state that the patient has TWO copies of the F508del mutation.

01/02/2025added

Added requirement that the patient meet at least one of: positive newborn screen, family history of CF, or clinical presentation consistent with CF.

01/02/2025added

Added requirement for evidence of abnormal CFTR function demonstrated by at least one of: elevated sweat chloride, two CF-causing CFTR mutations, or abnormal nasal potential difference.