Appeal type: Medical necessity
Decision: Overturned

Diagnosis: Type 2 Spinal Muscular Atrophy.
Treatment: Evrysdi .
The insurer denied Evrysdi. 
The determination is overturned.

The patient has been diagnosed with Type 2 Spinal Muscular Atrophy (SMA). He has 0 copies of SMN 1(survival motor neuron), and 3 copies of SMN 2. His motor milestones were delayed. After the diagnosis of SMA Type 2, he participated in the AveXis STRONG trial, receiving gene therapy (Zolgensma). His mother described improved motor function after treatment, but she described that he appeared to have plateaued or slightly regressed in his function. He started to receive risdiplam in the Roche Jewelfish trial, subsequently transitioning to commercial risdiplam. His mother describes that his strength improved, and that he is currently not progressing but is also not regressing.
He had an episode of acute respiratory failure. He was treated with bi-level positive airway pressure (BiPAP). He occasionally chokes with food, such as popcorn. He uses a percussive chest vest as needed. His medications include albuterol, vitamin D, MiraLax and risdiplam. He lives with his parents and four siblings. He has been using a power wheelchair.
A pulmonology note describes that his forced vital capacity (FVC) is mildly low, but forced expiratory volume in one second (FEV1), FEV1/forced vital capacity (FVC) and forced expiratory flow (FEF) 25-75% are all normal, consistent with very mild restrictive lung disease.
The neurological examination is significant for mildly low facial tone in the lower face, low-normal muscle bulk in the limbs, mild hip and knee contractures, low tone throughout, and generalized weakness.
At issue in this review is whether continued risdiplam is medically necessary.
The Evrysdi (risdiplam) is medically necessary for this patient.
He has Type 2 SMA. His strength and motor function improved after treatment with Zolgensma, but then plateaued and may have had some regression. He was started on risdiplam, and since then has stabilized with regard to his motor and respiratory function. If risdiplam was withdrawn, it is very likely that he would have further regression. He would be at risk of loss of functional skills, and of severe respiratory complications.
At present there is limited information in the medical literature regarding combination use of therapies in SMA. The RESPOND study is currently following a cohort of children previously treated with Zolgensma who are now receiving nusinersen, an antisense oligosacchardide that increases levels of SMN by modulating alternative splicing of the SMN2 gene, functionally converting it into SMN1 gene, thus increasing the level of SMN protein in the central nervous system (CNS). Similarly, risdiplam, an orally bioavailable messenger ribonucleic acid (mRNA) splicing modifier increases systemic SMN protein concentrations by improving the efficiency of SMN2 gene transcription.
Harada et al. [3] describe a series of 5 children with SMA who have received combination therapy (Zolgensma and nusinersen) but note that "[f]urther studies are needed to determine whether there are circumstances in which combination therapy would be more efficacious than either monotherapy." In another case series from Romania [3] the authors noted the same motor function in children who had received both therapies compared with those in the monotherapy cohort, noting that "the evolution of motor function was better in the 6 months following the first therapy than in the first 6 months after adding the second treatment."