Coverage Policies

Effective Date:

a)    This policy will apply to all services performed on or after the above revision date which will become the new effective date.

b)    For all services referred to in this policy that were performed before the revision date, contact customer service for the rules that would apply.

1)    Spinraza (Nusinersen) is approved by the FDA for the treatment of Spinal Muscular Atrophy (SMA)

2)    Initial requests for Spinraza (Nusinersen) require preauthorization to ensure the diagnosis of SMA has been confirmed by a neurologist or pediatric neurologist with the appropriate laboratory tests. 

3)    All preauthorization requests for Spinraza (Nusinersen) have a limit of only 6 months. 

4)    All requests for continuation of Spinraza (Nusinersen) beyond 6 months require a new preauthorization to ensure pediatric neurologist has documented clinically significant benefit from the therapy.

Initial Therapy***

Initial therapy with Spinraza/Nusinersen requires preauthorization and is considered medically necessary for the treatment of spinal muscular atrophy in individuals who meet criteria A AND B AND C:

1. SMA diagnosis of G12.0 (infantile spinal muscular atrophy, type 1) has been confirmed by a pediatric neurologist AND
2. Laboratory test documentation of diagnosis by either:
   1. SMA diagnostic test results confirming 0 copies of SMN1; or
   2. Molecular genetic testing of 5q SMA for any of the following:
      1. homozygous gene deletion; or
      2. homozygous conversion mutation; or
      3. compound heterozygote; AND
3. Documentation of either:
   1. Genetic testing confirming no more than 2 copies of SMN2; or
   2. SMA-associated symptoms before 6 months of age.

Continuation Therapy***

Continuation of treatment with Spinraza/Nusinersen beyond 6 months after initiation of therapy, and every 6 months thereafter, requires preauthorization and is considered medically necessary for the treatment of spinal muscular atrophy when individuals meet both criteria A AND B:

1. When initial therapy was determined to meet the above criteria, AND
2. When there is documentation (using objective findings such as the Hammersmith Functional Motor Scale or Hammersmith Infant Neurologic Exam) by a pediatric neurologist of clinically significant improvement in spinal muscular atrophy-associated symptoms (for example, progression, stabilization, or decreased decline in motor function) compared to the predicted natural history trajectory of disease.

*** If an individual meets medically necessary criteria, dosing of Spinraza/Neusinersen treatment is covered according to the Food and Drug Administration (FDA) product information label. The FDA recommends that a maintenance dose should be administered once every 4 months. As noted above, to continue therapy, medically necessary criteria requires pediatric neurologist to objectively evaluate and demonstrate Spinraza/Nusinersen`s clinical effectiveness for the treated individual every 6 months.

Codes Used In This BI:

Spinal Muscular Atrophy (SMA)

SMA is largely an inherited autosomal recessive disease caused by mutations in chromosome 5q that lead to a deficiency in SMN1-related proteins. In rare instances (2-3% of SMA), SMA can occur de novo, where a mutation occurs in an individual during egg or sperm production, rather than inheriting a defective copy of the gene from each parent. This deficiency results in degeneration of motor neurons causing muscle atrophy, particularly in the limbs and the muscles that control the mouth, throat and respiration. There are four types of SMA, types I, II, III, and IV which are defined based on the severity of muscle weakness and the age of symptom onset. SMA type I (Werdnig-Hoffmann disease) is the most severe. SMA type I-affected infants represent approximately 60% of SMA diagnoses and present with the disease by 6 months of age. These infants are profoundly hypotonic and often succumb to complications of the disease by their second year of life. SMA type II affected children (intermediate form) present with symptoms prior to 18 months of age and develop the ability to sit unaided but not the ability to stand or walk. Individuals affected by SMA type III (Kugelberg-Welander disease) are also generally diagnosed by 18 months but are able to stand and walk. SMA type III affected individuals may live into their thirties and beyond. SMA IV, the least severe, typically presents in the second or third decade of life, but is otherwise similar to type III.

SMN2, a closely related gene to SMN1 that also produces functional SMN, can compensate for SMN1 deficiency and modify the SMA phenotype. Therefore, although the role of SMN protein in motor neurons is not completely understood and the amount for normal functioning undefined, the phenotype of spinal muscular atrophy (type I, II, III, or IV) is largely related to the number of SMN2 gene copies present. The number of copies of SMN2 in individuals diagnosed with SMA has been found to negatively correlate with disease severity. For instance, infants diagnosed with SMA type I, are likely to have two copies or less of SMN2 and individuals with SMA type III and IV are likely to have three copies or more (Mailman, 2002).

A number of other motor neuron diseases exist, also termed SMA, that are caused by mutations in genes other than the SMN1 gene. These are referred to as non-5q- SMA diseases, meaning that the genes causing these forms of SMA are not located in the SMN region of chromosome 5.

The incidence of SMA is approximately 1 in 10,000 live births with an estimated carrier frequency of 1 in 50. Standard of care for SMA has historically been based on supportive therapy which includes nutrition, physical therapy, and respiratory assistance. SMA is the leading genetic cause of death in infants, but can affect individuals at any stage of life.

Neusinersen is an antisense oligonucleotide designed to treat SMA by altering SMN2 promoting increased production of functional SMN. Neusinersen is the first drug to receive FDA approval for the treatment of children and adults with SMA.

At this time there are convincing research studies showing benefits of Neusinersen for patients with SMA type I.  There are no studies yet for patients with SMA type IV and there are ongoing studies to determine potential benefits for patients with SMA type II and SMA type III.

1. Chiriboga CA, Swoboda KJ, Darras BT, et al. Results from a phase 1 study of Neusinersen (ISIS-SMN (Rx)) in children with spinal muscular atrophy. Neurology. 2016; 86(10):890-897.
2. Finkel RS, Chiriboga CA, Vajsar J, et al. Treatment of infantile-onset spinal muscular atrophy with Neusinersen: a phase 2, open-label, dose-escalation study. Lancet. 2016; 388(10063):3017-3026.
3. Finkel RS, McDermott MP, Kaufmann P, et al. Observational study of spinal muscular atrophy type I and implications for clinical trials. Neurology. 2014; 83(9):810-817.
4. Mailman M, Heinz J, Papp A, et al. Molecular analysis of spinal muscular atrophy and modification of the phenotype by SMN2. Genet Med. 2002; 4(1):20-26.