Colorado Rocky Mountain Health Plans Exondys 51 Coverage Update

Coverage Criteria for Exondys 51 (eteplirsen)

inv-01: Initial Therapy

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

Initial Therapy - all: 1) Diagnosis of Duchenne muscular dystrophy by, or in consultation with, a neurologist with expertise in DMD; 2) Submission of medical records confirming the DMD gene mutation is amenable to exon 51 skipping; 3) One of: 6MWT ≥ 300 meters while walking independently OR both: ambulatory without assistive device AND one of (NSAA score >17 OR time to rise <7 seconds); 4) Patient has not previously received gene therapy for DMD OR if previously received gene therapy, submission of records documenting a clinically meaningful functional decline since gene therapy; 5) Exondys 51 will not be used concomitantly with givinostat or other exon skipping therapies; 6) Dosing is in accordance with U.S. FDA-approved labeling; 7) Initial authorization will be for no more than 12 months.

inv-02: Continuation Therapy

Covered for continuation therapy when ALL of the following are met:

Continuation Therapy - all: 1) Submission of medical records confirming the patient remains ambulatory without needing an assistive device; 2) Exondys 51 is not used concomitantly with givinostat or other exon skipping therapies; 3) Prescribed by, or in consultation with, a neurologist with expertise in DMD; 4) Dosing is in accordance with U.S. FDA-approved labeling; 5) Reauthorization will be for no more than 12 months.

inv-03: Unproven / Not Medically Necessary

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

inv-04: Evidence-informed coverage considerations

Coverage considerations informed by available clinical evidence and FDA indication:

FDA indication: Patient has genetically confirmed Duchenne muscular dystrophy with a mutation amenable to exon 51 skipping.

FDA indication granted under accelerated approval based on increased dystrophin; continued approval may be contingent on confirmatory trials.

Clinical trial phenotype: Characteristics of trial-eligible patients (PROMOVI): male, age ~7–16 years, baseline 6MWT ≥ 300 m, FVC%p ≥ 50%, on stable corticosteroids.

These criteria reflect PROMOVI inclusion and inform expected candidate profile.

Evidence limitations: Randomized controlled data are limited; many studies lacked placebo control and relied on historical controls; clinical benefit remains uncertain.

The 201/202 studies did not demonstrate clinical benefit per prescribing information; PROMOVI was open-label and non-randomized.

Use of Exondys 51 (eteplirsen) outside the FDA-labeled population is limited by the policy. Specifically, the policy considers use in other forms of muscular dystrophy (for example, Becker muscular dystrophy) to be unproven and not medically necessary, and such uses are excluded from coverage. Documentation submitted for authorization must therefore confirm a diagnosis of Duchenne muscular dystrophy and a DMD gene mutation amenable to exon 51 skipping to meet coverage criteria.

The policy also prohibits concomitant administration of Exondys 51 with other exon-skipping therapies and with givinostat (Duvyzat). Providers seeking authorization should ensure medical records state whether any other exon skipping agent or givinostat is being prescribed or administered, because concomitant use with these agents is an exclusion and may result in denial.

A material policy revision effective 05/01/2026 explicitly added a prohibition on concomitant use of Exondys 51 with Duvyzat (givinostat). This means that requests for coverage that include co-administration of Exondys 51 and givinostat will not meet the policy’s coverage criteria and may be denied.

Providers must document that Exondys 51 will not be used concomitantly with Duvyzat; absence of clear documentation about concomitant givinostat use may trigger a request for additional records or denial under the policy’s concomitant therapy exclusion.

The policy states that eteplirsen is not medically necessary for treatment of other forms of muscular dystrophy, including Becker muscular dystrophy. Authorization should not be approved for those indications because they are considered unproven in this policy.

Eteplirsen is intended for patients with Duchenne muscular dystrophy whose genetic mutation is amenable to exon 51 skipping. Use in patients with DMD who do not have mutations amenable to exon 51 skipping is not supported by the clinical evidence cited in the policy and therefore would not meet medical necessity criteria.

Similarly, the policy does not support use of eteplirsen for other muscular dystrophies (e.g., Becker), reinforcing that coverage is limited to the genotype-specified DMD population described in the FDA indication and trial populations.

Initial Authorization Criteria

inv-27: Initial Therapy

Initial authorization criteria for Exondys 51

Initial therapy nodes: 1) Diagnosis by, or in consultation with, a neurologist with expertise in DMD; 2) Documentation of a DMD gene mutation amenable to exon 51 skipping; 3) Ambulation criteria: 6MWT ≥ 300 m while walking independently OR ambulatory without assistive device AND (NSAA >17 OR time to rise <7 s); 4) No prior gene therapy OR documented clinically meaningful functional decline if prior gene therapy; 5) No concomitant use with givinostat or other exon skipping therapies; 6) Dosing per U.S. FDA labeling; 7) Initial authorization ≤ 12 months.

inv-28: Initial therapy candidate profile

Initial therapy candidate profile — eligibility profile based on trial criteria

Genetic confirmation: Genotypically confirmed DMD mutation amenable to exon 51 skipping (matches FDA indication and trial inclusion).

Reauthorization and Continuation

inv-29: Reauthorization

Reauthorization requires confirmation of continued ambulatory status and adherence to other continuation criteria

Reauthorization - all: 1) Confirmation via medical records that the patient remains ambulatory without needing an assistive device; 2) Continued non-use of concomitant excluded agents (givinostat or other exon skipping therapies); 3) Prescribed by, or in consultation with, a neurologist experienced in DMD; 4) Dosing per U.S. FDA-approved labeling; 5) Reauthorization will be for no more than 12 months.

inv-30: Continuation considerations

Trial continuation outcomes and safety considerations — factors to inform continuation decisions

Observed long-term outcomes: At Week 96, eteplirsen-treated patients showed increased exon skipping and dystrophin versus baseline, with mean 6MWT decline from 374.6 m to 256.2 m, NSAA decline and attenuation of decline versus external controls; adverse events were generally mild to moderate and did not lead to treatment discontinuation.

These results inform continuation considerations; numeric thresholds for continued benefit are not specified in this extract.

Billing and Diagnosis Codes

HCPCS CodeHCPCS

J1428

Injection, eteplirsen, 10 mg

Diagnosis CodeICD-10

G71.01

Duchenne or Becker muscular dystrophy

6-Minute Walk Test (6MWT) — ambulatory threshold used in criteria

6MWT threshold6-Minute Walk Test (6MWT) ≥ 300 meters (ambulatory without assistance)

Alternative ambulatory evidenceDocumentation may include NSAA >17 or time to rise (TTR) <7 seconds when 6MWT not provided

Evidence source for thresholdPROMOVI trial required ability to walk ≥ 300 m on 6MWT for eligibility

6-Minute Walk Test (6MWT) — trial eligibility note

Trial eligibility notePROMOVI enrolled patients who were able to walk ≥ 300 m on the 6MWT

Age range in PROMOVIPatients were male, aged 7–16 years in PROMOVI

Provider Requirements and Authorization Process

Prior Authorization

Prior Authorization Required — Documentation of Genotype and Clinical Status

Prior authorization required. Documentation must confirm a diagnosis of Duchenne muscular dystrophy (DMD) and that the patient’s DMD gene mutation is amenable to exon 51 skipping. Authorization requests should include medical records (e.g., chart notes, laboratory results, genetic test reports) demonstrating the amenable genotype, prescriber specialty (neurologist with expertise in DMD or documentation of consultation), ambulatory status, and other clinical measures described below. Initial authorizations are limited to 12 months; reauthorization (continuation) is limited to 12 months.

Submit genetic testing confirming a mutation amenable to exon 51 skipping
Include chart notes showing prescriber is a neurologist with expertise in DMD or documentation of consultation
Provide evidence of ambulatory status (see clinical criteria below) and relevant functional measures (6MWT, NSAA, TTR)
Attach prior medical records, lab values, and any prior gene therapy details if applicable

Step Therapy and Sequencing

Step	Requirement / Restriction
1	Concomitant use of Exondys 51 with Duvyzat (givinostat) or other exon‑skipping therapies for DMD (e.g., Amondys, Viltepso, Vyondys 53) is not allowed.

Step	Notes
1	No specific step‑therapy sequence or upstream agents are specified in this policy extract; policy revisions updated coverage criteria but did not add step edits.

Administration and Infusion Setting

Billing Rule

Infusion center — IV administration per prescribing information

Intravenous administration is the route used for eteplirsen per prescribing information; site-of-care considerations should reflect infusion capability (e.g., infusion center).

Eteplirsen is administered IV per prescribing information
Plan site-of-care for outpatient infusion capability

Note

Infusion center — weekly IV infusion details and site considerations

In clinical trials (PROMOVI), eteplirsen was administered as a weekly IV infusion of 30 mg/kg given over approximately 35–60 minutes; infusion setting should accommodate weekly infusions of this duration.

Dose used in PROMOVI: 30 mg/kg IV weekly

Background on Duchenne Muscular Dystrophy and Eteplirsen

Duchenne muscular dystrophy (DMD) is an X-linked, progressive muscle-wasting disorder caused by mutations in the dystrophin gene that typically leads to loss of ambulation in childhood and progressive cardiopulmonary decline. Eteplirsen is an antisense oligonucleotide designed to induce exon 51 skipping to produce an internally truncated, partially functional dystrophin protein; approximately a minority of DMD patients have mutations amenable to exon 51 skipping.

Clinical trials cited in the policy (including PROMOVI and earlier 201/202 studies) focused on ambulatory male patients with genotypically confirmed mutations amenable to exon 51 skipping and used functional thresholds such as the 6-minute walk test (≥ 300 m) and pulmonary function (FVC%p ≥ 50%) to define trial-eligible patients. The evidence base is limited and includes non-randomized and historical-control comparisons, and the FDA granted eteplirsen accelerated approval based on a surrogate endpoint (dystrophin increase) with continued approval contingent on verification of clinical benefit.

Definitions and Key Terms

Eteplirsen — definition and mechanism

DefinitionEteplirsen (Exondys 51) — an antisense oligonucleotide designed to bind to exon 51 of dystrophin pre-mRNA to produce exclusion of exon 51 during mRNA processing

Therapeutic goalExon 51 skipping allows production of an internally truncated dystrophin protein

Patient populationIntended for patients with DMD who have genetic mutations amenable to exon 51 skipping (≈13% of DMD patients)

NSAA — North Star Ambulatory Assessment definition

DefinitionNorth Star Ambulatory Assessment (NSAA) — a functional scale used to assess motor abilities in ambulatory DMD patients

Policy thresholdPolicy references NSAA score >17 as one criterion supporting ambulatory status for initiation

OpenPayer

Exondys 51 (eteplirsen) — Coverage Criteria for Duchenne Muscular Dystrophy