CurrentConnectiCarePolicy C25469-A

Daybue (trofinetide) for Rett syndrome

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Pharmacy coverage and prior authorization for oral Daybue in adults and pediatric members age 2 years and older with typical or classic Rett syndrome, subject to diagnosis, MECP2 mutation, weight, severity, monitoring, and continuation-response requirements.

Policy Summary

PayerConnectiCare

PolicyDaybue (trofinetide) for Rett syndrome

Policy CodePolicy C25469-A

Change TypeNo material clinical or coverage change

Effective DateJune 11, 2026

Next Review DateApril 1, 2027

Key ActionSubmit prior authorization with documentation of typical or classic Rett syndrome, an MECP2 mutation, weight of at least 9 kg, a qualifying baseline RTT score, and baseline symptoms.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

2+ yearsMinimum age

9 kgMinimum weight

12 monthsInitial authorization

12 monthsContinuation authorization

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CurrentConnectiCarePolicy C25469-A

Daybue (trofinetide) for Rett syndrome

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Get alerted when Policy C25469-A changes without checking for updates manually.

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Policy Summary

PayerConnectiCare

PolicyDaybue (trofinetide) for Rett syndrome

Policy CodePolicy C25469-A

Change TypeNo material clinical or coverage change

Effective DateJune 11, 2026

Next Review DateApril 1, 2027

Key ActionSubmit prior authorization with documentation of typical or classic Rett syndrome, an MECP2 mutation, weight of at least 9 kg, a qualifying baseline RTT score, and baseline symptoms.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

2+ yearsMinimum age

9 kgMinimum weight

12 monthsInitial authorization

12 monthsContinuation authorization

Common adverse reactions

Coverage Criteria

Initial Therapy

Covered for initial therapy when all of the following are met.

Initial therapy requirements

Diagnosis and genetic confirmation: Documentation confirms classical or typical Rett syndrome and a mutation of the MECP2 gene.
Age and weight: The member is 2 years of age or older and weighs at least 9 kilograms.Age >=2 years; weight >=9 kg
Baseline RTT clinical score
- Documentation of a baseline Rett Syndrome Behaviour Questionnaire (RSBQ) total score.
- Documentation of a baseline Clinical Global Impression Severity (CGI-S) score of 4 or greater.CGI-S >=4
Baseline signs and symptoms: The prescriber documents baseline signs and symptoms, such as hand skills and movements, speech, and gait.
Qualified prescriber: Daybue is prescribed by, or in consultation with, a neurologist or physician experienced in managing Rett syndrome.
Consultation notes are required when prescribed in consultation.

Continuation Therapy

Covered for continuation therapy when all of the following are met.

Continuation requirements

Positive clinical response from baseline
- The RSBQ total score is reduced from baseline.
- The CGI-S score is reduced from baseline.
- The CGI-I score is less than 4.CGI-I <4
- The prescriber documents improvement in Rett syndrome signs and symptoms, such as hand skills and movements, speech, or gait.

All uses of Daybue (trofinetide) other than the covered Rett syndrome indication are considered experimental or investigational and are subject to the applicable off-label policy.

Coding and Clinical Thresholds

HCPCS CODE DESCRIPTIONHCPCS

NA	AVAILABLE DOSAGE FORMS: Daybue SOLN 200MG/ML; Daybue Stix PACK 5000MG, 6000MG, 8000MG

Minimum Member Weight

Minimum weightAt least 9 kilograms

Applies toInitial Daybue coverage

Related age requirementMember must be at least 2 years of age

CGI-S Baseline Severity

Baseline thresholdCGI-S score of 4 or greater

ScaleClinical Global Impression Severity is a 7-point clinician-completed scale

Qualifying useMay be used as one qualifying baseline RTT clinical score for initial coverage

Provider Requirements and Authorization

Prior Authorization

Specialist Prescribing and Prior Authorization

Prior authorization is required for Daybue (trofinetide). The drug must be prescribed by, or in consultation with, a neurologist or physician experienced in managing Rett syndrome.

If prescribed in consultation, submit the consultation notes with the initial request and each reauthorization request.

Note

12-Month Authorization Periods

Authorization is issued for 12 months at a time for both initial therapy and continuation of therapy.

Initial authorization: 12 months
Continuation authorization: 12 months

Background

Rett syndrome is a rare neurodevelopmental disorder caused by mutations in the X-linked MECP2 gene and primarily affects females. Characteristic features include loss of acquired hand use and expressive language, gait abnormalities, and stereotypic hand movements. Disease progression may also involve seizures, breathing and coordination problems, cardiac arrhythmias, muscle weakness, reduced mobility, scoliosis, and gastrointestinal or behavioral complications.

Clinical Definitions and Assessment Measures

Rett Syndrome Behaviour Questionnaire (RSBQ)

Completed byCaregiver

Format45-item rating scale assessing Rett syndrome signs and symptoms; maximum total score is 90

InterpretationLower scores indicate lesser severity of signs and symptoms

Clinical Global Impression Severity (CGI-S)

Completed byClinician

PurposeRates severity of illness

Range7-point scale from 1 (normal) to 7 (among the most extremely ill patients)

Initial Therapy Criteria

Initial Therapy

Initial coverage requires all diagnosis, genetic, weight, severity, symptom, age, and qualified-prescriber requirements.

Initial Daybue therapy

Diagnosis and genetic confirmation
- Documentation of classical or typical Rett syndrome.
- Documentation that the member has a mutation of the MECP2 gene.
Weight and age: Documentation that the member weighs at least 9 kilograms and is 2 years of age or older.Age >=2 years; weight >=9 kg
One qualifying baseline RTT clinical score

Continuation Criteria

Continuation Therapy

Continuation requires documented response and tolerability.

Continuation therapy

Positive clinical response from baseline
- Reduction in the Rett Syndrome Behaviour Questionnaire (RSBQ) total score from baseline.
- Reduction in the Clinical Global Impression Severity (CGI-S) score from baseline.
- Clinical Global Impression Improvement (CGI-I) score of less than 4.CGI-I <4
- Other prescriber documentation of improvement in Rett syndrome signs and symptoms, such as hand skills and movements, speech, or gait.

Daybue Quantity Limits

Daybue Quantity Limit

Member weight9 kg to <12 kg

Recommended dose5,000 mg twice daily

Oral solution volume25 mL twice daily

Daybue Quantity Limit

Member weight12 kg to <20 kg

Recommended dose6,000 mg twice daily

Oral solution volume30 mL twice daily

Site of Care

Note

Use pharmacy benefit and self-administration for oral medication

Oral medication is recommended for pharmacy benefit coverage and patient self-administration.

Policy Summary

PayerConnectiCare

PolicyDaybue (trofinetide) for Rett syndrome

Policy CodePolicy C25469-A

Change TypeNo material clinical or coverage change

Effective DateJune 11, 2026

Next Review DateApril 1, 2027

Key ActionSubmit prior authorization with documentation of typical or classic Rett syndrome, an MECP2 mutation, weight of at least 9 kg, a qualifying baseline RTT score, and baseline symptoms.

SourceLink

On This Page

Safety and tolerability:

The prescriber attests to, or the clinical reviewer finds, no evidence of intolerable adverse effects or drug toxicity.

If diarrhea or weight loss occurs, refer to FDA-labeled guidance.

Documentation Required

Initial Clinical Documentation

Submit the following documentation with the initial request for Daybue coverage:

Diagnosis of classical or typical Rett syndrome
Documentation of a mutation of the MECP2 gene
Member weight of at least 9 kilograms
One baseline Rett syndrome clinical score: Rett Syndrome Behaviour Questionnaire (RSBQ) total score or Clinical Global Impression Severity (CGI-S) score of 4 or greater
Prescriber documentation of baseline signs and symptoms, such as hand skills and movements, speech, gait, and other relevant Rett syndrome manifestations

Documentation Required

Continuation Documentation

For continuation and reauthorization, document a positive clinical response from baseline and that treatment remains tolerable.

Improvement shown by a reduction in the RSBQ total score, reduction in the CGI-S score, a CGI-I score less than 4, or other prescriber documentation of improvement in signs and symptoms
Prescriber attestation or clinical reviewer finding that there is no intolerable adverse effect or drug toxicity
Address diarrhea or weight loss according to FDA-labeled guidance when applicable

Documentation Required

Submit Consultation Notes

When the prescription is issued in consultation with a qualified specialist, consultation notes are required with both the initial request and reauthorization requests.

Include the neurologist's or experienced Rett syndrome physician's consultation notes when applicable.

Documentation Required

Additional Review Documentation

ConnectiCare may request additional information to complete medical-necessity, coverage, quality-improvement, or fraud, waste, and abuse review.

Patient medical records
Test results and clinical scores
Credentials of the provider ordering or performing the service
Member-specific dosing data, including weight, body surface area, or other required measurement when dosing is based on it
Other case-specific information needed for adequate review

Denial Risk

Required Medical Information Is Missing

Missing required clinical information may prevent approval or result in denial of the request. Ensure the record supports the diagnosis and all applicable eligibility and severity requirements.

Classical or typical Rett syndrome diagnosis
MECP2 mutation documentation
Weight of at least 9 kilograms
Required baseline severity score: RSBQ or CGI-S of at least 4
Baseline signs and symptoms and, for continuation, documented clinical improvement
Required response, tolerability, and reauthorization information

Denial Risk

Non-Rett or Other Uses

Daybue (trofinetide) is covered under this policy for the specified Rett syndrome criteria. All other uses are considered experimental or investigational and are subject to the applicable off-label policy.

Do not submit non-Rett or other uses as covered indications under this section.

Denial Risk

Unsupported Medical Necessity or Billing

ConnectiCare may deny reimbursement or take other appropriate plan action when submitted documentation does not support medical necessity, non-investigational status, benefit eligibility, or appropriate billing and utilization.

Provide complete medical rationale for any requested exception.
Documentation must support that the drug or service is medically necessary and within the member's benefits.
Inadequate, inappropriate, or excessive billing or other unsupported practice may result in denial or additional plan action.

Clinical Global Impression Improvement (CGI-I)

Completed byClinician

PurposeRates treatment-related change from baseline

Range and interpretation7-point scale from 1 (very much improved) to 7 (very much worse); 4 indicates no change from baseline

Typical or Classic Rett Syndrome

Disease courseA period of regression followed by recovery or stabilization

Main criteriaPartial or complete loss of acquired purposeful hand skills; partial or complete loss of acquired spoken language; impaired or absent gait; and stereotypic hand movements

ExclusionsBrain injury secondary to trauma, neurometabolic disease, or severe infection causing neurological problems; or grossly abnormal psychomotor development in the first 6 months of life

Supportive criteriaNot required, although often present in typical Rett syndrome

Documentation of a baseline Rett Syndrome Behaviour Questionnaire (RSBQ) total score.
Documentation of a baseline Clinical Global Impression Severity (CGI-S) score of 4 or greater.CGI-S >=4

Baseline symptoms: The prescriber documents baseline signs and symptoms, including, for example, hand skills and movements, speech, and gait.

Qualified prescriber: Daybue is prescribed by, or in consultation with, a neurologist or physician experienced in the management of Rett syndrome.

If prescribed in consultation, consultation notes must be submitted with the initial request.

Tolerability: The prescriber attests to, or the clinical reviewer has found, no evidence of intolerable adverse effects or drug toxicity.

If diarrhea or weight loss occurs, refer to FDA-labeled guidance.

Daybue Quantity Limit

Member weight20 kg to <35 kg

Recommended dose8,000 mg twice daily

Oral solution volume40 mL twice daily

Daybue Quantity Limit

Member weight35 kg to <50 kg

Recommended dose10,000 mg twice daily

Oral solution volume50 mL twice daily

Daybue Quantity Limit

Member weight50 kg or greater

Recommended dose12,000 mg twice daily

Oral solution volume60 mL twice daily