CurrentCignaPolicy IP0508

Antiseizure Medications - Ztalmy

This policy governs prior authorization and coverage criteria for Ztalmy (ganaxolone oral suspension) for treatment of seizures associated with CDKL5 deficiency disorder for Cigna-administered health benefit plans and specifies documentation and prescriber requirements.

Policy Summary

PayerCigna

PolicyAntiseizure Medications - Ztalmy

Policy CodePolicy IP0508

Change TypeDocumentation addedtitle revised

Effective DateSep 15, 2025

Next Review DateN/A

Key ActionObtain prior authorization and provide required documentation including molecular confirmation of a pathogenic or likely pathogenic CDKL5 variant and evidence of trial or concomitant use of at least two antiseizure medications.

SourceLink

POLICY UPDATE CHANGES

Updated coverage policy title from 'Ganaxolone' to 'Antiseizure Medications - Ztalmy'.

Added documentation requirements throughout policy.

≥2minimum patient age for FDA indication

1 yrinitial approval duration

≥2required tried/concomitant ASMs

n=101Marigold trial enrollment

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Seizures associated with CDKL5 deficiency disorder

Ztalmy is considered medically necessary when ALL of the following are met:

FDA-Approved Indication for Ztalmy: A) Patient is ≥ 2 years of age;

FDA-Approved Indication for Ztalmy: B) Patient has a molecularly confirmed pathogenic or likely pathogenic variant in the CDKL5 gene [documentation required];

FDA-Approved Indication for Ztalmy: C) Patient has tried and/or is concomitantly receiving at least two other antiseizure medications [documentation required];

FDA-Approved Indication for Ztalmy: D) The medication is prescribed by or in consultation with a neurologist.

Approve for 1 year if all met.

Ztalmy (ganaxolone) is not covered for indications outside those specified in this policy. Specifically, Ztalmy for any other use is considered not medically necessary. Coverage will be limited to uses described in the FDA‑approved indication and the criteria in this policy; criteria will be updated if new published data become available.

Use of Ztalmy for indications other than seizures associated with Cyclin‑Dependent Kinase‑Like 5 (CDKL5) deficiency disorder is not medically necessary and is excluded from coverage under this policy. Requests for Ztalmy must meet the specific coverage criteria for seizures related to CDKL5 deficiency disorder to be considered for approval.

Provider Actions, Prior Authorization, and Documentation

Prior Authorization

Prior Authorization Required

Prior authorization is required for benefit coverage of Ztalmy. Approvals are provided for the duration noted in the clinical criteria (approve for 1 year when criteria are met). Ztalmy must be prescribed by or in consultation with a physician who specializes in the condition being treated (e.g., neurologist).

Approve for 1 year when criteria met
Must be prescribed by or in consultation with a specialist (neurologist)

Denial Risk

Denial Triggers and Required Documentation

Claims submitted without a covered diagnosis or without required documentation will be denied. Prior authorization is required for coverage; failure to obtain prior authorization will result in denial. Documentation requested in the criteria (marked [documentation required]) must be provided and may include chart notes, laboratory or medical test results, genetic test reports confirming a pathogenic or likely pathogenic CDKL5 variant, prescription receipts, and other relevant records.

Claims without covered diagnosis or without required documentation will be denied
Prior authorization required for coverage; lack of prior authorization will result in denial
Provide documentation where criteria indicate [documentation required] (e.g., genetic testing confirming CDKL5 variant, records of prior/concomitant antiseizure medications)

Background

CDKL5 deficiency disorder (CDD) is a rare, X‑linked developmental epileptic encephalopathy characterized by early‑onset seizures, hypotonia, and severe neurodevelopmental delay. Most patients present with seizures in infancy and seizures are often refractory to treatment. Ztalmy (ganaxolone) is approved for the treatment of seizures associated with CDD in patients aged ≥ 2 years. This policy defines the coverage criteria, prior authorization requirements, and documentation needed to support medical necessity for Ztalmy in this population.

Definitions

inv-09: CDKL5 deficiency disorder (CDD) — definition, genetic cause, clinical presentation summary

DefinitionA rare, X-linked developmental epileptic encephalopathy caused by pathogenic or likely pathogenic variants in the CDKL5 gene.

Genetic causePathogenic or likely pathogenic variants (mutations) in the CDKL5 gene affecting the CDKL5 protein (a kinase important for brain and neuron development).

Typical clinical presentationEarly-onset seizures (≥90% before 3 months; median ~5 weeks), hypotonia, intractable/refractory epilepsy, and severe neurodevelopmental delay affecting cognitive, motor, speech, and visual function.

Epidemiology noteAlthough cases occur in boys, CDD primarily affects girls due to the gene's location on the X chromosome.

Prognosis/seizure controlSeizure freedom is uncommon: <50% have seizure-free periods >2 months and only ~12% achieve >12 months seizure freedom.