Is continuation of Exondys 51 (eteplirsen) treatment medically necessary for an 18-year-old male with Duchenne muscular dystrophy (DMD) due to deletion of exon 50, who lost ambulation at age 12 and uses a power wheelchair (PWC) and manual wheelchair (MWC)?

Continuation of Exondys 51 is NOT Medically Necessary for This Patient

Continuation of eteplirsen (Exondys 51) should NOT be approved for this 18-year-old non-ambulatory patient with DMD, as he fails to meet the critical continuation criteria of remaining ambulatory—the primary evidence-based endpoint for demonstrating treatment response. 1

Critical Analysis of Continuation Criteria

Patient Does NOT Meet Continuation Requirements

The patient explicitly fails the essential continuation criterion established by evidence-based guidelines:

• Ambulatory Status Requirement: The patient lost ambulation at age 12 and is now wheelchair-dependent (both PWC and MWC use), requiring maximum assistance with transfers 1
• Continuation Criteria: Guidelines specify that continuation requires "remaining ambulatory (e.g., able to walk with or without assistance, not wheelchair dependent)" 1
• Duration of Non-Ambulatory Status: The patient has been non-ambulatory for 6 years (since age 12), well beyond any reasonable expectation of treatment benefit 1

Patient Also Failed Initial Approval Criteria

Beyond continuation criteria, this patient would not have qualified for initial approval under current evidence-based standards:

• Age at Initiation: Treatment should be "initiated before the age of 14," but continuation is being requested at age 18 for a patient who lost ambulation at 12 1
• Baseline Functional Capacity: Initial approval requires "an average distance of at least 180 meters while walking independently over 6 minutes"—this patient cannot walk at all 1

Evidence Base for Ambulatory-Only Benefit

Clinical Trial Data Support Ambulatory Patients Only

The evidence supporting eteplirsen demonstrates benefit exclusively in ambulatory populations:

• Primary Endpoint: Clinical trials measured 6-minute walk test (6MWT) distance as the key functional outcome, requiring patients to walk 200-400 meters at baseline 2
• Treatment Effect: Eteplirsen-treated patients showed a 67.3-meter benefit on 6MWT compared to placebo, but this outcome is only measurable in ambulatory patients 2
• PROMOVI Trial: The phase 3 study confirmed attenuation of decline on 6MWT (-68.9 m vs -133.8 m in controls), again requiring ambulatory function 3

No Evidence for Non-Ambulatory Benefit

• Lack of Data: No clinical trials have demonstrated dystrophin production translates to functional benefit in non-ambulatory DMD patients receiving eteplirsen 2, 3
• Cardiac Limitations: Unmodified PMOs (like eteplirsen) have "limited efficacy in the heart," which becomes the primary concern in non-ambulatory patients 4

Appropriate Management for Non-Ambulatory DMD Patients

Glucocorticoid Therapy Remains Indicated

Glucocorticoids should be continued even after loss of ambulation, as they provide benefits distinct from exon-skipping therapy:

• Scoliosis Prevention: Glucocorticoids reduce "progressive scoliosis and need for spinal surgery" in non-ambulatory patients 1
• Pulmonary Function: They "stabilize pulmonary function and delay need for noninvasive ventilation" 1
• Cardiac Protection: Continued steroid use may help delay cardiac complications 5, 1
• Dosing: Continue prednisone 0.75 mg/kg/day or deflazacort 0.9 mg/kg/day (maximum 30 mg/day or 36 mg/day respectively at 40 kg body weight) 5, 1

Multidisciplinary Non-Ambulatory Care

For this 18-year-old non-ambulatory patient, focus should shift to:

• Cardiac Management: ACE inhibitors or ARBs should be established by age 10, with β-blockers added as needed for ventricular dysfunction 1
• Respiratory Support: Regular pulmonary function monitoring, sleep studies for hypoventilation, and consideration of noninvasive ventilation 1
• Scoliosis Management: Given the patient's documented scoliosis requiring updated seating mold, surgical evaluation may be warranted if Cobb angle reaches 30-50 degrees 1
• Physical/Occupational Therapy: Continue PT/OT to maintain range of motion, prevent contractures, and optimize wheelchair positioning 5, 1
• Bone Health: Monitor for fractures (patient has history of multiple healed LE fractures), ensure adequate vitamin D and calcium, consider bisphosphonates 5

Common Pitfalls to Avoid

• Continuing Ineffective Therapy: Maintaining eteplirsen in non-ambulatory patients wastes resources without evidence of benefit and may give false hope to families 2, 3
• Neglecting Proven Therapies: Discontinuing glucocorticoids prematurely in non-ambulatory patients deprives them of proven benefits for scoliosis, pulmonary function, and potentially cardiac outcomes 1
• Missing Cardiac Surveillance: At age 18, cardiac management becomes paramount—ensure ACE inhibitor/ARB and β-blocker therapy is optimized 1
• Inadequate Respiratory Monitoring: Non-ambulatory patients require vigilant pulmonary function testing and sleep studies to time noninvasive ventilation appropriately 1