CurrentCignaPolicy CNF979

Zycubo Prior Authorization Policy - (CNF979)

Defines medical necessity and prior authorization criteria for coverage of Zycubo (copper histidinate subcutaneous injection) for treatment of Menkes disease in pediatric patients, including required diagnostic confirmation, prescriber specialty, approval durations, and explicit noncovered indication (Occipital Horn Syndrome).

Policy Summary

PayerCigna

PolicyZycubo Prior Authorization Policy - (CNF979)

Policy CodePolicy CNF979

Change TypeMaterial revisions (age requirement and prescriber list)

Effective Date

Next Review Date

Key ActionPrior Authorization is recommended; document diagnostic confirmation or testing-in-progress, document patient is under 17 years, and ensure prescriber is a geneticist, neonatologist, neurologist, or Menkes disease specialist.

SourceLink

POLICY UPDATE CHANGES

Specialist requirement updated to include a neonatologist.

Requirement that the patient is < 18 years of age was added.

Age requirement modified to < 17 years of age.

1Covered Indication (Menkes disease)

1Not Covered Indication (Occipital Horn Syndrome)

4Acceptable Prescriber Specialties

Coverage Summary

Scope: This policy defines prior authorization criteria for Zycubo (copper histidinate subcutaneous injection) for the treatment of Menkes disease in pediatric patients. The policy covers Zycubo for Menkes disease when all diagnostic and prescriber requirements are met and specifies approval durations based on diagnostic evidence.

Not covered: The policy explicitly states Zycubo is not indicated for Occipital Horn Syndrome (OHS) (a milder phenotype of Menkes disease).

Prescriber requirement: Zycubo must be prescribed by or in consultation with a geneticist, neonatologist, neurologist, or a specialist who focuses on the treatment of Menkes disease (neonatologist was added as an acceptable prescriber).

Age limit: Therapy is limited to pediatric patients < 17 years of age per the policy criteria.

Approval durations: Approvals vary by diagnostic evidence — 1 year if diagnosis is confirmed by molecular genetic testing or plasma catecholamine analysis; 1 month if the prescriber documents that testing is in progress and the patient has findings suggestive of Menkes disease.

Thresholds and Quick Facts

Plasma dopamine/norepinephrine ratio> 0.2

Dihydroxyphenylacetic acid/dihydroxyphenylglycol ratio> 5

Age requirement< 17 years

Acceptable prescriber specialties (count)4

Acceptable prescriber specialties (list)Geneticist, neonatologist, neurologist, or a specialist who focuses on treatment of Menkes disease

Medical Necessity Criteria

FDA-Approved Indication - Menkes Disease (Initial Approval)

Approve for the duration noted if the patient meets ALL of the following (A, B, and C):

ALL of the following

A: Patient is < 17 years of age
Diagnosis established by ONE of the following
- i: Molecular genetic test demonstrating a pathogenic or likely pathogenic variant in the ATP7A gene
  Approval duration: 1 year
- ii: Plasma catecholamine analysis findings that are consistent with the diagnosis
  Approval duration: 1 year
- iii: Prescriber states the patient has findings suggestive of Menkes disease and genetic testing or plasma catecholamine analysis is in progress
  Approval duration: 1 month
C: Medication is prescribed by or in consultation with a geneticist, neonatologist, neurologist, or a specialist who focuses on the treatment of Menkes disease

Not Covered Indications

Zycubo is not indicated for Occipital Horn Syndrome (OHS). The policy explicitly lists OHS as a condition for which Zycubo is considered not medically necessary.

Definition note: OHS is described as a milder phenotype of Menkes disease (i.e., a less severe clinical presentation of ATP7A-related copper transport disorder).

Provider Actions & Authorization Requirements

Prior Authorization

Prior authorization required

Prior Authorization is recommended for prescription benefit coverage of Zycubo. Approvals are provided for specified durations depending on the diagnostic evidence submitted.

Documentation Required

Diagnostic confirmation required

Document one of the following: molecular genetic test showing a pathogenic or likely pathogenic variant in ATP7A, plasma catecholamine analysis findings consistent with Menkes disease (see diagnostic ratios), or documentation from the prescriber that testing (genetic testing or plasma catecholamine analysis) is in progress for approvals limited to 1 month.

Documentation Required

Age documentation

Document that the patient is under 17 years of age.

Documentation Required

Specialist involvement required

Zycubo must be prescribed by or in consultation with a geneticist, neonatologist, neurologist, or a specialist who focuses on the treatment of Menkes disease. (Note: a recent revision added neonatologist to the list of acceptable prescribers.)

Geneticist
Neonatologist
Neurologist
Specialist who focuses on treatment of Menkes disease

Background, Evidence & Definitions

Zycubo is a copper replacement product indicated for treatment of Menkes disease in pediatric patients, with dosing specified for patients < 17 years of age.

Menkes disease overview: Menkes disease is an X-linked ATP7A-related copper transport disorder presenting in infancy with seizures, failure to thrive, developmental delay, and systemic manifestations; classical disease is the most severe phenotype and accounts for the majority of cases.

Diagnostic considerations: Serum copper and ceruloplasmin are often low in Menkes disease but are not diagnostic in infants < 6 months and therefore are not used independently. Confirmatory testing is by plasma catecholamine ratios (diagnostic if dopamine/norepinephrine > 0.2 or dihydroxyphenylacetic acid/dihydroxyphenylglycol > 5) or by molecular genetic testing for pathogenic/likely pathogenic ATP7A variants. Plasma catecholamine analysis may not be available at all centers; genetic testing is recommended when catecholamine testing is unavailable.

Timing and treatment recommendation: For infants with classical Menkes disease, a systematic review and expert consensus recommend early initiation of subcutaneous copper histidinate therapy during the neonatal period (before 30 days of life) with treatment continued indefinitely for classical disease. This guidance is supported by the prescribing information and guideline recommendation cited in the policy.

Term	Definition
Menkes disease diagnostic plasma catecholamine ratios
Plasma dopamine/norepinephrine ratio > 0.2 OR dihydroxyphenylacetic acid/dihydroxyphenylglycol ratio > 5 (values recognized as diagnostic for Menkes disease)
Occipital Horn Syndrome (OHS)
A milder phenotype of Menkes disease for which Zycubo is not indicated

Policy Summary

PayerCigna

PolicyZycubo Prior Authorization Policy - (CNF979)

Policy CodePolicy CNF979

Change TypeMaterial revisions (age requirement and prescriber list)

Effective Date

Next Review Date

SourceLink

On This Page

OpenPayer

Zycubo Prior Authorization Policy - (CNF979)

Coverage Summary

Medical Necessity Criteria

Not Covered Indications

Provider Actions & Authorization Requirements

Coding

Background, Evidence & Definitions

Revision History