CurrentBlue Cross Blue Shield - IowaPolicy 05.05.05

Daybue (trofinetide) for Rett syndrome — Coverage Criteria

This policy governs prior authorization, coverage criteria, dosing limits, and documentation requirements for Daybue (trofinetide) for members with Rett syndrome under Wellmark Blue Cross and Blue Shield plans.

Policy Summary

PayerBlue Cross Blue Shield - Iowa

PolicyDaybue (trofinetide) for Rett syndrome — Coverage Criteria

Policy CodePolicy 05.05.05

Change TypeRoutine review — no material changes

Effective DateJul 14, 2023

Next Review DateJun 14, 2025

Key ActionSubmit prior authorization with genetic confirmation of MECP2 mutation and baseline RSBQ or CGI-S; initial approvals may be granted for 6 months when criteria are met.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

2 yearsminimum age

6 moinitial approval

12 mocontinuation approval

8 bottles/30dquantity limit

Coverage Criteria for Daybue (trofinetide)

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Initial Therapy

Covered when ALL of the following are met for initial approval:

Initial Approval Criteria: A. Member is 2 years of age or older; B. Diagnosis of classic or typical Rett Syndrome confirmed by meeting ALL of: (1) partial or complete loss of acquired purposeful hand skills; (2) partial or complete loss of acquired spoken language; (3) gait abnormalities: impaired or absence of ability; (4) stereotypic hand movements such as hand wringing/squeezing, clapping/tapping, mouthing, and washing/rubbing automatisms; C. Confirmed mutation in the MECP2 gene; D. Documentation of at least one baseline assessment score: Rett Syndrome Behavioral Questionnaire (RSBQ) OR Clinical Global Impression-Severity (CGI-S).none

Authorization of 6 months may be granted when these are met

Continuation Therapy

Covered when ALL of the following are met for continuation:

Continuation Approval Criteria: Member meets Initial Approval criteria (A through C) AND: A. Member is experiencing a positive clinical response to therapy (e.g., stabilization or improvement of repetitive movements, mood dysfunction/disruptive behavior, vocalization, ambulation); B. Member meets ONE of: (1) Improvement on RSBQ from baseline; (2) CGI-I score of <= 4; (3) Improvement on CGI-S from baseline. Note: Baseline RSBQ and CGI-S are not required if CGI-I is provided for continuation.none

Authorization of 12 months may be granted when these are met

Provider Actions, Prior Authorization, and Documentation

Prior Authorization

Prior authorization required — initial 6 months; continuation 12 months

Prior authorization is required for Daybue (trofinetide). When all initial approval criteria are met, authorization of 6 months may be granted; continuation approvals may be granted for 12 months when continuation criteria are met (initial criteria plus documented clinical response and required assessment improvements).

Initial authorization: up to 6 months when Criteria for Initial Approval are met
Continuation authorization: up to 12 months when Criteria for Initial Approval are met and continuation criteria (positive clinical response and required assessment improvement) are documented

Step Therapy

Prescriber specialty or consultation required

The medication must be prescribed by or in consultation with a neurologist, geneticist, or developmental pediatrician experienced in the treatment of Rett syndrome.

Documentation Required

Required documentation for initial and continuation requests

Initial prior authorization requests must include genetic testing confirming an MECP2 mutation and a baseline assessment score (RSBQ or CGI‑S). Continuation requests must include medical records documenting a positive clinical response and assessment scores (RSBQ, CGI‑S, or CGI‑I) showing stabilization or improvement from baseline.

Initial: genetic testing results confirming MECP2 mutation
Initial: baseline RSBQ or CGI‑S score
Continuation: medical records documenting positive clinical response (e.g., stabilization or improvement of repetitive movements, mood/disruptive behavior, vocalization, ambulation)
Continuation: RSBQ, CGI‑S, or CGI‑I scores demonstrating stabilization or improvement from baseline

Denial Risk

Denial risk if coverage criteria are not met

Daybue (trofinetide) is considered not medically necessary and will be denied if the member does not meet the specified initial and continuation criteria.

Members must meet all elements of the Criteria for Initial Approval (age ≥2 years; diagnostic features of classic/typical Rett syndrome; confirmed MECP2 mutation; documented baseline RSBQ or CGI‑S) to be eligible
Continuation requires meeting initial criteria plus documented positive clinical response and one of the specified assessment improvements

Background

Daybue (trofinetide) is FDA-approved for the treatment of Rett syndrome in patients aged 2 years and older and is addressed in this policy for use consistent with that indication. Prior authorization is required; when all initial criteria are met, authorization of 6 months may be granted for initial therapy, and when continuation criteria are met, authorization of 12 months may be granted. The policy requires genetic confirmation of an MECP2 mutation and baseline assessments (RSBQ or CGI-S) for initial requests, and documentation of a positive clinical response with specified assessment improvements for continuation.

Definitions and Assessment Scales

Rett syndrome indication

IndicationDaybue (trofinetide) is indicated for the treatment of Rett syndrome in patients 2 years of age and older

Age thresholdMinimum age for coverage: 2 years

Confirmation requiredDiagnosis must meet criteria for classic/typical Rett syndrome and include confirmed MECP2 mutation per initial criteria

RSBQ and CGI scales

RSBQRett Syndrome Behavioral Questionnaire: 45 items across 8 categories; each item scored 0–2 (0=never true, 1=sometimes true, 2=always true); total score range 0–90, higher scores indicate greater severity

CGI-SClinical Global Impression–Severity: 7-point clinician-rated scale assessing illness severity (1=normal, 7=extreme illness)

CGI-IClinical Global Impression–Improvement: 7-point clinician-rated scale assessing change since last evaluation (1=very much improved, 4=no change, 7=very much worse)