UnitedHealthcare Exondys 51 Coverage Update

Coverage Criteria for Exondys 51 (eteplirsen)

Initial Therapy

Covered when ALL of the following are met

Initial Therapy: Diagnosis of Duchenne muscular dystrophy by, or in consultation with, a neurologist with expertise in the diagnosis of DMD

Genetic confirmation: Submission of medical records (e.g., chart notes, laboratory values) confirming the mutation of the DMD gene is amenable to exon 51 skipping

Baseline ambulation/function: Either: submission of medical records confirming the patient has a 6-Minute Walk Test (6MWT) ≥ 300 meters while walking independently OR both: submission of medical records confirming the patient is ambulatory without needing an assistive device AND one of the following — NSAA score > 17 OR time to rise (TTR) < 7 seconds6MWT ≥ 300 m; NSAA > 17; TTR < 7 s

Children must be ambulatory per criteria

Gene therapy status: Either patient has not previously received gene therapy (e.g., Elevidys) OR patient previously received gene therapy and submission of medical records documents a clinically meaningful functional decline (loss of muscle strength/motor ability) since receiving gene replacement therapy

Documentation required if prior gene therapy

Therapy restrictions and prescribing: Exondys 51 will not be used concomitantly with Duvyzat (givinostat) or other exon skipping therapies; prescribed by, or in consultation with, a neurologist with expertise in the treatment of DMD; dosing in accordance with FDA-approved labeling; initial authorization for no more than 12 months

Initial Therapy

Covered when ALL of the following are met

Population and diagnosis: Patient has Duchenne muscular dystrophy with a confirmed DMD gene mutation amenable to exon 51 skipping

Supported by FDA indication and PROMOVI enrollment criteria

Baseline clinical status: Patient has stable pulmonary function: percent predicted forced vital capacity (FVC%p) ≥ 50%, not requiring nocturnal ventilation, and unlikely to decompensate during treatmentFVC%p ≥ 50%

PROMOVI inclusion criteria

Functional ability at baseline: Patient is ambulatory and able to walk ≥ 300 meters on the 6-minute walk test (6MWT)6MWT ≥ 300 m

PROMOVI inclusion criteria

Continuation Therapy / Reauthorization

Covered when ALL of the following are met

Ongoing ambulation: Submission of medical records (e.g., chart notes) confirming that the patient is ambulatory without needing an assistive device (e.g., without side-by-side assist, cane, walker, wheelchair, etc.)

Reauthorization / Continuation

Reauthorization requires documentation of maintained ambulatory status and adherence to prescribing and dosing restrictions

Reauthorization criteria: Patient remains ambulatory without assistive device; not receiving disallowed concomitant therapies (e.g., Duvyzat or other exon skipping agents); continued prescribing by or in consultation with a DMD-experienced neurologist; dosing per FDA labeling; reauthorization for no more than 12 months

Documentation (chart notes) required

Continuation Therapy

Covered when ALL of the following are met

Treatment monitoring: Clinical benefit is uncertain; ongoing monitoring of functional endpoints (e.g., 6MWT, NSAA, FVC%p) is expected for assessment of continued therapy

PROMOVI showed attenuation of decline but uncertain clinical significance

Unproven / Not Medically Necessary

Unproven indications: Exondys 51 is unproven and not medically necessary for the treatment of other forms of muscular dystrophy (e.g., Becker muscular dystrophy)

Coverage for Exondys 51 (eteplirsen) is limited to use as a single agent and will not be used concomitantly with Duvyzat (givinostat) or other exon skipping therapies for DMD (for example, Amondys, Viltepso, Vyondys 53). Documentation must confirm prescribing by, or in consultation with, a neurologist experienced in DMD and dosing consistent with the FDA label. Initial authorizations are limited to no more than 12 months.

Eteplirsen has been studied only in patients with Duchenne muscular dystrophy who have genotypically confirmed mutations amenable to exon 51 skipping. The PROMOVI trial enrolled male patients aged 7–16 years with mutations amenable to exon 51 skipping and required baseline stability criteria (including FVC%p ≥ 50% and ability to walk ≥ 300 m on the 6-minute walk test). Eteplirsen has not been studied in patients with DMD who have mutations not amenable to exon 51 skipping.

Use of Exondys 51 (eteplirsen) for other forms of muscular dystrophy, including Becker muscular dystrophy, is considered unproven and not medically necessary.

Requests for eteplirsen to treat patients without mutations amenable to exon 51 skipping or to treat other dystrophies are not supported by the available evidence and will not be approved. The policy explicitly prohibits concomitant use with Duvyzat (givinostat) and other exon skipping agents, and this exclusion may lead to denial if concomitant therapy is documented.

Initial Therapy and Dosing Requirements

Initial Therapy / Authorization

Initial authorization is granted when genetic and functional eligibility, prescribing, and documentation requirements are met.

Initial authorization: Diagnosis by, or in consultation with, a neurologist with expertise in DMD; documentation of mutation amenable to exon 51 skipping; baseline ambulation/function criteria met (6MWT ≥ 300 m OR ambulatory without assistive device AND (NSAA > 17 OR TTR < 7 s)); no prior or acceptable prior gene therapy documentation as specified; not used concomitantly with disallowed agents (e.g., Duvyzat or other exon skipping therapies); dosing in accordance with FDA-approved labeling; initial authorization for no more than 12 months

Submission of medical records required

Initial Therapy Dosing

Initial dosing and population from clinical studies

Dose: Intravenous infusion of 30 mg/kg once weekly administered over approximately 35–60 minutes30 mg/kg weekly

Continuation and Reauthorization Criteria

Reauthorization / Continuation

Reauthorization requires documentation of maintained ambulatory status and adherence to prescribing and dosing restrictions

Reauthorization criteria: Patient remains ambulatory without needing an assistive device; not receiving disallowed concomitant therapies; continued prescribing by or in consultation with a DMD-experienced neurologist; dosing per FDA labeling; reauthorization for no more than 12 months

Submission of chart notes required

Continuation Therapy

Continuation/assessment

Treatment monitoring: Clinical benefit is uncertain; ongoing assessment of functional endpoints (e.g., 6MWT, NSAA, FVC%p) is expected to evaluate continued therapy

PROMOVI results showed attenuation of decline over 96 weeks; monitor for maintained ambulatory status

Coding and Clinical Thresholds

HCPCS CodeHCPCS

J1428

Injection, eteplirsen, 10 mg

Diagnosis CodeICD-10

G71.01

Duchenne or Becker muscular dystrophy

6-Minute Walk Test — Threshold for Eligibility

6MWT threshold≥ 300 meters

ContextMeasured while walking independently (no side-by-side assist, cane, walker, wheelchair, etc.)

Documentation requiredSubmission of medical records (e.g., chart notes, laboratory values) confirming 6MWT result prior to initiating Exondys 51

6-Minute Walk Test (6MWT) Baseline Requirement

Baseline requirement>= 300 meters on the 6MWT prior to study entry or treatment initiation

Supporting trial criteriaPROMOVI required ability to walk ≥ 300 m on the 6MWT (male patients aged 7–16 years)

Provider Actions, Documentation, and Denial Triggers

Prior Authorization

Prior Authorization Required

Prior authorization is required. Submit prior authorization request with documentation of diagnosis, genetic testing confirming a DMD gene mutation amenable to exon 51 skipping, and evidence of neurologist involvement. Include baseline functional assessments (e.g., 6-Minute Walk Test, North Star Ambulatory Assessment, time to rise) as specified in the policy. Initial and reauthorization approvals are limited to periods of up to 12 months.

Affected plans: UnitedHealthcare Commercial and Individual Exchange benefit plans
Initial authorization: up to 12 months; Reauthorization: up to 12 months
Required documentation: medical records/chart notes, laboratory values, genetic test results confirming exon 51 amenability, neurologist consultation notes, baseline functional test results (6MWT, NSAA, TTR as applicable)

Denial Risk

Denial Triggers

Coverage may be denied if required information is missing or exclusion criteria are met. Key denial triggers include: lack of documentation confirming an exon 51–amenable DMD mutation; absence of required baseline or ongoing functional documentation; prior or concurrent use of excluded therapies; or failure to document neurologist prescribing/consultation.

Step Therapy / Therapy Restrictions

Step	Requirement / Restriction	Coverage status
1
Exondys 51 will not be used concomitantly with Duvyzat (givinostat) or other exon skipping therapies for DMD (e.g., Amondys, Viltepso, Vyondys 53).
Concomitant use prohibited; coverage denied if used together

Step	Policy change	Coverage status
1
Policy revised to add an exclusion specifying Exondys 51 will not be used concomitantly with Duvyzat (givinostat); the revision operationalizes an exclusion rather than describing a step-therapy sequence.
Exclusion in effect — concomitant use with specified agent is not covered

Background on Duchenne Muscular Dystrophy and Eteplirsen

Duchenne muscular dystrophy (DMD) is an X-linked progressive muscle degeneration disorder caused by mutations in the dystrophin gene that result in loss of ambulation and life-limiting cardiopulmonary complications. Eteplirsen is an antisense oligonucleotide that targets exon 51 to induce exon skipping and produce an internally truncated dystrophin protein; approximately 13% of patients with DMD have mutations amenable to exon 51 skipping. Clinical trials of eteplirsen (including PROMOVI, a 96‑week, open‑label study) evaluated weekly intravenous dosing of 30 mg/kg and required patients to have stable pulmonary function (FVC%p ≥ 50%) and baseline ambulatory ability (ability to walk ≥ 300 m on the 6‑minute walk test). Trial results demonstrated increased exon skipping and dystrophin expression but provided uncertain clinical benefit, with attenuation of decline on functional measures over 96 weeks and no conclusive demonstration of meaningful clinical improvement.

Definitions and Regulatory Context

Exon 51 Skipping / Eteplirsen Mechanism

MechanismEteplirsen is an antisense oligonucleotide that binds to exon 51 of dystrophin pre-mRNA to exclude exon 51 during mRNA processing

GoalExon 51 skipping permits production of an internally truncated dystrophin protein in patients with amenable mutations

PrevalenceApproximately 13% of DMD patients have deletion mutations amenable to exon 51 skipping

Accelerated Approval — FDA Basis

Approval pathwayExondys 51 approved under accelerated approval by FDA based on an increase in dystrophin in skeletal muscle

RequirementContinued approval may be contingent upon verification of clinical benefit in confirmatory trials

OpenPayer

Exondys 51 (eteplirsen) — Medical Benefit Drug Policy (coverage criteria)

Coverage Criteria for Exondys 51 (eteplirsen)

Initial Therapy and Dosing Requirements

Continuation and Reauthorization Criteria

Coding and Clinical Thresholds

Provider Actions, Documentation, and Denial Triggers

Step Therapy / Therapy Restrictions

Background on Duchenne Muscular Dystrophy and Eteplirsen

Definitions and Regulatory Context