Is continued therapy with Amondys 45 (casimersen) medically necessary for a 15-year-old male with Duchenne muscular dystrophy (DMD) who is wheelchair-bound?

Continued Casimersen (Amondys 45) Therapy is NOT Medically Necessary Based on Current Evidence-Based Criteria

Based on the Aetna clinical policy bulletin and FDA-approved indication, continuation of casimersen therapy is not medically necessary for this wheelchair-bound patient, as the evidence-based criterion requiring ambulatory status is not met, despite the previous lifetime appeal.

Critical Analysis of the Authorization Criteria

Aetna's Evidence-Based Continuation Criteria

The Aetna CPB 0911 for gene-based therapy in DMD explicitly requires both of the following for continuation 1:

1. The patient must remain ambulatory (able to walk with or without assistance, not wheelchair-dependent) - NOT MET
2. The patient must not exceed 30 mg/kg once weekly - MET (2100mg weekly for estimated weight meets dosing)

The Fundamental Problem with This Case

• This 15-year-old male is wheelchair-bound and cannot walk, which directly contradicts the continuation criterion requiring ambulatory status 1
• The previous lifetime appeal (REF [ID]) was granted when different clinical circumstances may have existed, but current evidence-based criteria must be applied to current functional status 1

Evidence Base for the Ambulatory Requirement

Why Ambulatory Status Matters for Casimersen Efficacy

The FDA approval of casimersen was based on dystrophin production as a surrogate endpoint, NOT on functional outcomes in non-ambulatory patients 2, 3. The critical evidence gaps include:

• No RCT data demonstrate functional benefit in wheelchair-bound patients - all pivotal trials measured dystrophin production, not clinically meaningful outcomes in non-ambulatory populations 4
• The phase 1/2 trial included participants with "limited ambulation or were nonambulatory" but was designed to assess safety and pharmacokinetics, not functional efficacy 4
• Casimersen received accelerated FDA approval contingent on ongoing phase III trials demonstrating clinical benefit - this approval pathway acknowledges uncertainty about real-world functional outcomes 3

The Distinction from Corticosteroid Therapy

This case fundamentally differs from corticosteroid continuation in non-ambulatory DMD patients:

• Corticosteroids have proven benefits in non-ambulatory patients: moderate quality evidence shows they retard scoliosis progression, stabilize pulmonary function, and may delay heart failure even after loss of ambulation 5, 1, 6
• The Lancet Neurology guidelines explicitly recommend continuing glucocorticoids when non-ambulatory for these documented benefits 5, 1
• No comparable evidence exists for casimersen in non-ambulatory patients - the mechanism (dystrophin production) does not translate to proven functional or survival benefits once wheelchair-bound 2, 3

Clinical Context and Alternative Management

What This Patient Actually Needs

For a 15-year-old wheelchair-bound DMD patient, evidence-based priorities should focus on interventions with proven morbidity and mortality benefits 5:

1. Respiratory management - noninvasive ventilation has proven survival benefits and improved quality of life in non-ambulatory DMD 5
2. Cardiac protection - ACE inhibitors/ARBs initiated by age 10 with proven mortality benefits 1
3. Continued corticosteroid therapy - if tolerated, for scoliosis prevention and pulmonary function stabilization 5, 1
4. Aggressive airway clearance - mechanical insufflation-exsufflation to prevent respiratory complications 5

The Provider's Letter of Medical Necessity

While the provider states "risks/symptoms are greater than side effects," this clinical judgment must be weighed against:

• Casimersen has excellent safety profile (mostly mild, unrelated adverse events) 4, so the issue is not safety but rather lack of proven efficacy in this population
• The patient is "stable" per provider notes - stability does not demonstrate that casimersen is providing benefit versus natural disease course
• Unchanged echocardiogram - this cardiac stability is more attributable to standard cardiac management (ACE inhibitors/ARBs) than to casimersen 1

The Lifetime Appeal Consideration

Why Previous Appeals Don't Override Current Evidence-Based Criteria

The reference to "lifetime appeal per REF [ID]" creates a precedent problem but does not supersede medical necessity determination based on current functional status:

• Appeals are typically granted based on circumstances at the time of appeal - if the patient was ambulatory or transitioning to wheelchair dependence at that time, the clinical context has now changed
• Medical necessity must be reassessed based on current evidence and current functional status, not historical decisions 1
• The Aetna policy specifically notes: "Members who were previously established on Amondys 45 and subsequently administered gene replacement therapy must meet all initial criteria prior to re-starting" - this demonstrates that continuation is not automatic regardless of prior authorization 1

Recommendation and Rationale

Primary Recommendation

Casimersen continuation should not be authorized for this wheelchair-bound patient because:

1. The patient fails to meet the evidence-based continuation criterion of remaining ambulatory - this is an objective, measurable criterion 1
2. No high-quality evidence demonstrates functional benefit, quality of life improvement, or survival benefit in non-ambulatory DMD patients treated with casimersen 2, 4, 3
3. Resources should be redirected to interventions with proven mortality and morbidity benefits in non-ambulatory DMD patients 5, 1

Alternative Management Plan

Ensure this patient receives evidence-based therapies with proven benefits 1:

• Verify continued corticosteroid therapy (if not contraindicated)
• Confirm cardiac protection with ACE inhibitors/ARBs and beta-blockers as indicated
• Assess need for noninvasive ventilation (polysomnography with CO2 monitoring) 5
• Ensure access to mechanical insufflation-exsufflation for airway clearance 5
• Regular pulmonary function monitoring and cardiology follow-up 1

Critical Caveat

If the provider can document that the patient was ambulatory at the time of the lifetime appeal and has only recently become wheelchair-bound, consideration might be given to a time-limited continuation (e.g., 3-6 months) to assess for any decline in upper extremity function or other measurable outcomes. However, this would require prospective functional outcome measures and predetermined criteria for discontinuation if no benefit is demonstrated.