Appeal type: Medical necessity
Decision: Overturned

Diagnosis: Duchenne Muscular Dystrophy
Treatment: Exondys-51 500 (mg) 10(mg) VIAL
The insurer denied the Exondys-51 500 (mg) 10(mg) VIAL.
The denial is overturned.

The patient is a male with Duchenne Muscular Dystrophy. He has a DMD (Duchenne Muscular Dystrophy) gene mutation with an exon 49-50 deletion. This mutation is amenable to exon 51 skipping. The patient currently receives treatment with Emflaza. He has some behavioral side effects to Emflaza. He is able to run with occasional falls with tripping. He does toe walk. He is beginning to become more tired with sustained running. He can climb stairs unassisted and change his own clothes. His neurologist requested Exondys.

The request for Exondys was denied coverage by the health plan due to the patient's age. The plan requires an age of 7-13 years old for Exondys use. The neurologist appealed this decision and stated that the past studies of Exondys use in patients 7 and older were designed in that manner because patient cooperation was imperative. He stated that studies patients 4-6 years old are ongoing and based on the mechanism of action, earlier administration is likely to maximize the drug benefit.

Yes, the requested Exondys is medically necessary.
Current standards of care for Duchenne Muscular Dystrophy include steroids for patients who are not amenable to exon skipping. Patients who have mutations amenable to exon skipping are deemed appropriate candidates for the therapy (Muller-York, Iftikhar). These drugs, including Exondys, are FDA (United States Food and Drug Administration) approved for this diagnosis and are considered a standard of care treatment. The FDA (United States Food and Drug Administration) approved Exondys use based on the demonstration of increased dystrophin production in patients who received it.

The plan denied Exondys due to plan requirements of a minimum age of 7 years old to initiate the drug. As the requesting physician discussed, earlier use of Exondys is expected to provide a greater benefit, as the patient will have more retained dystrophin. A recently published open label study comparing patients receiving Exondys vs natural history matched controls included patients receiving Exondys since as early as 7 years old. The evidence supported attenuation of clinical decline. Randomized controlled clinical studies for Exondys use with patients as young as 4 years old are recruiting (MIS51ON). However, the FDA (United States Food and Drug Administration) approval was not based on a clinical benefit, but was based on an increase in dystrophin levels in the musculature. Per the Exondys FDA (United States Food and Drug Administration) label, the safety data includes studies with patients as young as 4 years of age. The most common adverse events were balance problems, vomiting, and contact dermatitis.

In summary, Exondys is FDA (United States Food and Drug Administration) approved for treatment of Duchenne Muscular Dystrophy in patients who have mutations amenable to exon 51 skipping. The approval was based on demonstration of increased dystrophin levels in muscle. Thus as the drug addresses the direct pathophysiology of the disease and the FDA (United States Food and Drug Administration) indication was approved without proving a direct clinical benefit (for patients of any age), the main question about determining medical necessity is in regards to safety data. As discussed above, patients as young as 4 years old received the medication. Therefore Exondys is medically necessary in this case.

No, the health plan did not act reasonably, with sound medical judgment, and in the best interest of the patient.
There is some controversy over Exondys and similar drugs due to the FDA (United States Food and Drug Administration) approval that did not depend on demonstration of a direct clinical benefit to patients. As discussed above, recent studies are showing a potential benefit when patients, as young as 7 years old, are compared to matched natural history controls. However, this data is not from controlled studies, thus is not definitive. Based on the pathophysiology of the disease and the mechanism of action, patients younger than 7 years old are expected to have a greater benefit than those older, because younger patients will not have lost as much muscle mass due to being earlier in the course of the progressive disease.  Randomized studies are pending to confirm this benefit from Exondys. The plan decision to deny the drug thus hinges on safety data. The studies the FDA (United States Food and Drug Administration) based their decision to approve Exondys on included patients as young as 4 years old. Thus, there is very limited clinical data to support Exondys use in any age, but there exists safety data to support Exondys as young as 4 years old. As the denial was based on an age requirement, the safety data from the FDA (United States Food and Drug Administration) label should be sufficient to determine the patient may use Exondys.