Appeal type: Medical necessity
Decision: Overturned

Diagnosis: Spinal Muscular Atrophy
Treatment: Pharmacy/Prescription Drugs/Evrysdi SGM
The health plan denied the requested prescription drug/Evrysdi. The health plan's determination is overturned.

The patient is a girl who was diagnosed with spinal muscular atrophy (SMA) type 1. The condition was confirmed genetically; she was found to have 0 copies of the SMN1 (Survival Motor Neuron) gene and 2 copies of the SMN2 gene. A letter by her pediatric neuromuscular specialist describes that she started Nusinersen (Spinraza), the first approved drug for SMA, when she was 1 year old. She has received 13 doses, with documented improvement of her scores on the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorder (CHOP INTEND). At baseline, prior to Nusinersen, her score was 28/64, improving to 36/64 after 9 doses of Nusinersen, and to 38/64 after 10 doses of Nusinersen. The specialist describes that the patient has been doing well overall. Although she has a tracheostomy and is receiving ventilatory support, she has had no hospital admissions for pulmonary issues. She has had no recent illnesses. She is making progress with development, being able to say several words. The patient has gained motor milestones, and is able to grasp objects with both hands, and can tolerate sitting and lying prone for short periods of time.
The specialist notes that the patient's prognosis is stable with continued treatment. He would like to transition her from Nusinersen to Risdiplam (EVRYSDI SGM). Nusinersen is given intrathecally, by lumbar puncture, which is invasive. EVRYSDI is given orally, and also provides the potential for additional protective pulmonary function as it has improved systemic distribution compared with Nusinersen.
At issue in this review is whether Evrysdi SGM is medically necessary for the patient.

The health plan's determination of medical necessity is overturned, in whole.

The requested health service/treatment of Evrysdi SGM is medically necessary for this patient. 
The patient has SMA1, a progressive neuromuscular disease that is typically fatal within the first few months of life. She has had a good response to Nusinersen, with documented improvement of her CHOP-INTEND score, and stabilization of her respiratory function. Evrysdi SGM has a similar mechanism of action to Nusinersen, but has the significant advantages of being given orally, and of improved systemic availability, which will potentially give additional respiratory improvement. The alternative, continuation of Nusinersen, is more invasive, requiring repeated lumbar punctures and sedation. It may also be a less effective treatment than Risdiplam, as it has lower systemic distribution.
Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterized by degeneration of spinal motor neurons. The condition causes significant morbidity and mortality in affected children, who have profound weakness affecting the limbs and also the respiratory muscles. SMA is caused by low levels of survival motor neuron (SMN) protein owing to deletions or mutations of the SMN1 gene [1] An almost identical gene SMN2, present on the same chromosome, produces a smaller, truncated protein (SMN2) because of skipping of exon 7 from translation due to translation silent C6U (6th position substitution in exon 7) of SMN2 pre-mRNA (Messenger Ribonuecleic Acid) transcript. Only 10% of the SMN2 mRNAs produce full length SMN2 protein by including exon 7 in healthy individuals. A large deletion or sometimes a point mutation in SMN1 gene is responsible for SMA. In this case the number of copies of SMN2 genes in an individual determines the severity of disease (the more the number of copies the less severe the disease) [2].
In December 2016, Nusinersen (Spinraza) was approved by the Federal Drug Administration (FDA) in the United States [2], providing the potential for correction of SMN2 exon 7 splicing as a treatment for SMA. Nusinersen is an antisense oligonucleotide that targets intronic splicing silencer N1 (ISS-N1). Subsequently, in August 2020, Risdiplam, (Evrysdi SGM) an orally administered, small-molecule SMN2 pre-mRNA splicing modifier that distributes into the central nervous system (CNS) and peripheral tissues., was approved by the FDA as a treatment for SMA [3,4]. Poirier et al [3] describe that "in vitro and in vivo preclinical data strongly suggest that functional SMN protein increases seen in patients' blood following Risdiplam treatment should reflect similar increases in functional SMN protein in the central nervous system, muscle, and other peripheral tissues."