• For treatment of Duchenne muscular dystrophy (DMD) in patients who have a confirmed mutation of the DMD gene that is amenable to exon 51 skipping

• Diagnosis of DMD with mutation amenable to exon 51 skipping confirmed by genetic testing

AND

• Prescribed by or in consultation with a neurologist

AND

• Currently stable on an oral corticosteroid regimen for at least 6 months, unless contraindicated or member has experienced clinically significant adverse effects
  
  

• Non-FDA approved indications, which are not listed in the Health Net Approved Indications and Usage Guidelines section, unless there is sufficient documentation of efficacy and safety in the published literature.

• A clinical benefit of Exondys 51 has not been established. Continued FDA approval may be contingent upon verification of a clinical benefit in confirmatory trials. 
• Exondys 51 was approved based on an observed increase in dystrophin in skeletal muscle (primarily measured as percentage of dystrophin-positive fibers). Currently there is no clear threshold for the amount of dystrophin increase required to produce clinical benefit. Previous research has suggested dystrophin levels of at least 20-29% of normal are needed to avoid muscular dystrophy, and levels of at least 10% of normal can produce a more mild form of dystrophy. It is important to note that at week 180 of Exondys 51’s pivotal study, eteplirsen-treated patients had mean dystrophin levels that were only 0.93% of normal per Western blot analysis. Furthermore, the reliability of this pivotal study has been called into question by the FDA Office of Drug Evaluation’s director  and the FDA’s chief scientist, who both called for retraction of the study. To date, the study has not been retracted.
• Corticosteroids are routinely used off-label in DMD management with established efficacy in slowing decline of muscle strength and function (including motor, respiratory, and cardiac). They are recommended for all DMD patients per the American Academy of Neurology (AAN) and DMD Care Considerations Working Group; in addition, the AAN guidelines have been endorsed by the American Academy of Pediatrics, the American Association of Neuromuscular & Electrodiagnostic Medicine, and the Child Neurology Society.
• Prednisone is the corticosteroid with the strongest evidence. A second corticosteroid used in DMD is deflazacort, which is currently only available in the US through an expanded access program. 
• Examples of positive response to Exondys 51 therapy can include increased dystrophin levels, improvement in 6 minute walk test (6MWT) distance, objective muscle strength exams (possibly evaluated on a scale of 0-5, with 0 being no motion and 5 being full strength), quality of life surveys, time to wheelchair use, ability to rise from supine position, ability to ambulate, and respiratory parameters (such as forced vital capacity (FVC)% predicted and peak cough flow). Delayed disease progression may be determined by comparing patient data against natural history cohort data. Historically, DMD patients have an annual decrease in FVC of 5% and an annual decrease in MIP (maximal inspiratory pressure) and MEP (maximal expiratory pressure) of 4%. Furthermore, 50% of DMD patients lose ambulation by 12.5 years of age.

Vial: 100 mg/2 mL (50 mg/mL) and 500 mg/10 mL (50 mg/mL)

1. Exondys 51. Prescribing Information. Cambridge, MA: Sarepta Therapeutics, Inc; September 2016. Available at www.exondys51.com. Accessed October 7, 2016.

2. Bushby K, Finkel R, Birnkrant DJ, et al. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management. Lancet Neurol. 2010; 9(1): 77-93.

3. Gloss D, Moxley RT, Ashwal S, Oskoui M. Practice guideline update summary: corticosteroid treatment of Duchenne muscular dystrophy. Neurology. 2016; 86: 465-472.