Appeal type: Medical necessity
Decision: Upheld

Diagnosis: Duchenne Muscular Dystrophy
Treatment: Vyondys
The insurer denied Vyondys.
The determination is upheld.


The patient has Duchenne Muscular Dystrophy. He presented with severe delay in the acquisition of motor milestones. Laboratory data revealed a markedly increased serum level of creatine kinase (CK). This led to genetic testing, which revealed a pathogenic variant consistent with Duchenne Muscular Dystrophy (DMD).
The patient's specific pathogenic variant is deletion of exons 45-52 within the dystrophin gene. Based on this specific mutation, his physician, a neuromuscular specialist, has suggested that the patient should receive treatment with Vyondys 53, with the goal of slowing progression of his DMD symptoms. At issue is the medical necessity of the Vyondys.

Vyondys is not medically necessary for this patient.  He has Duchenne Muscular Dystrophy, which is an X-linked disorder that causes degeneration of skeletal and cardiac muscle. This muscle degeneration leads to progressive somatic muscle weakness and cardiomyopathy. Because the disease progresses to profound weakness and cardiac dysfunction, the disorder is ultimately and universally fatal. Duchenne Muscular Dystrophy is a genetic disorder that leads to lack of dystrophin in muscle cells. The absence of dystrophin destabilizes muscle membranes, which induces muscle cell degeneration and muscle cell loss. It is the loss of muscle cells that underlies the weakness and atrophy of muscles in affected patients. The patient's specific mutation in the dystrophin gene is deletion of exons 45-52.
Vyondys 53 (golodirsen) is a new potential therapy for Duchenne Muscular Dystrophy. It may prove to be useful for a specific subset of DMD patients who have a mutation of the dystrophin gene that is amenable to exon 53 skipping. Vyondys 53 produces its potential therapeutic effect by binding to exon 53 of dystrophin pre-mRNA, thus excluding this exon during messenger (mRNA) processing. As a result, Vyondys 53 allows production of a truncated form of the dystrophin protein that does not contain the mutated region. The presence of this truncated protein might allow muscle cells to function and survive better than they would with no dystrophin protein at all. The Food and Drug Administration (FDA) has granted accelerated approval of Vyondys 53 specifically for those DMD patients who have a confirmed mutation of the dystrophin gene that is amenable to exon 53 skipping. However, this accelerated FDA approval was not based on evidence of clinical benefit. Instead, the approval was based on the surrogate measure of an increase in dystrophin in skeletal muscle. The assumption was that a small increase in the presence of dystrophin might lead to improved clinical outcome. However, there have been no published studies demonstrating that there actually is an improved clinical outcome from Vyondys 53. Further studies are necessary before any conclusion can be reached regarding the clinical utility of Vyondys 53. The prescribing information for Vyondys 53 states explicitly that continued approval from the FDA may be contingent upon verification of a clinical benefit in confirmatory trials. Thus, the evidence that Vyondys 53 is clinically beneficial for patients with DMD does not exist. Clinical trials of Vyondys 53 have shown a statistically significant increase in muscle cell content of dystrophin in affected patients. However, the studies have not revealed a clinically useful benefit of Vyondys 53. It is unclear whether the small, but statistically significant increases in dystrophin would translate into clinical benefit.