Anthem Blue Cross California Spinraza (nusinersen) Form

Overview

This document addresses the use of Spinraza (nusinersen), a drug approved by the Food and Drug Administration (FDA) for the treatment of children and adults with spinal muscular atrophy (SMA). SMA is a rare and often fatal autosomal recessive genetic disease affecting muscle strength and movement. SMA is caused by a deficiency in SMN (survival motor neuron) 1-related proteins resulting from either deletion of both SMN1 genes, or mutations within the SMN1 gene. 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. SMA is most often diagnosed by an SMN1 gene deletion test using PCR but can also be detected by genetic testing of the SMN1 gene itself. SMA is one of the leading genetic causes of death in infants but can affect individuals at any stage of life.

Spinal Muscular Atrophy Classification

• SMA Type
  • 0
  • I
  • II
  • III
  • IV
• Predicted SMN2 Copy Number
  • 0-1
  • 1-3
  • 2-4
  • 2-4
  • >4
• Age of Onset
  • Prenatal
  • 0-6 months
  • <18 months
  • >18 months
  • >5 years to adult
• Life Expectancy
  • <6 months
  • <2 years
  • 10-40 years
  • Adult
  • Adult
• Highest motor function
  • None; require respiratory support
  • Never sit
  • Sit alone
  • Stand alone; walk assisted
  • Stand alone; walk unassisted

The five main types of SMA are defined based on the severity of muscle weakness and the age of symptom onset.

Clinical criteria

Coding

Document history

References

SMA type and severity of disease can correlate with the number of copies of the SMN2 gene. SMN2 is a closely related gene to SMN1; thus, this increased production can compensate for the genetic SMN1 deficiency and modify the SMA phenotype to be potentially less severe. While the number of copies of SMN2 can correlate and predict disease severity and type, the relationship is not exact, and exceptions can occur. Importantly, patients are confirmed as belonging to an SMA type retrospectively, based on the motor milestones they achieve. Treatment decisions must be made early in the disease, when only genetic information, and possibly initial clinical characteristics, are known. Current treatment for SMA may include supportive care, Spinraza (nusinersen), Zolgensma (onasemnogene abeparvovec-xioi), or Evrysdi (risdiplam). Evrysdi (risdiplam) in an mRNA splicing modifier administered orally daily while Zolgensma is a one-time gene therapy treatment. All three drug treatments were studied in separate but overlapping populations. The optimal treatment for eligible patients is unknown. The efficacy, safety, and clinical utility of concomitant treatment with Spinraza, Evrysdi, and/or Zolgensma is also unknown.

Spinraza (nusinersen) is an antisense oligonucleotide drug administered by intrathecal injection that modifies splicing of the SMN2 gene to increase production of normal, full-length survival motor neuron (SMN) proteins. To date, benefits of Spinraza have been demonstrated in two major phase-3 studies: Nusinersen versus Sham Control in Infantile-Onset Spinal Muscular Atrophy (ENDEAR trial) and Nusinersen versus Sham Control in Later-Onset Spinal Muscular Atrophy (CHERISH trial). Relevant inclusion criteria are shown in the table below.

Trial Information

ENDEAR Trial

• Diagnosis:
  • Homozygous deletion or mutation in the SMN1 gene
• Number of SMN2 copies / Symptom Onset:
  • 2 copies
  • <6 months of age
• Age:
  • <7 months

CHERISH Trial

• Diagnosis:
  • Homozygous deletion, mutation, or compound heterozygote in SMN1 gene
• Other Results:
  • 88% had 3 copies
  • 100% of participants had symptom onset before 21 months of age
• Age:
  • 2-12 years
• Clinical Criteria:

Clinical Criteria for Coverage

When a drug is being reviewed for coverage under a member’s medical benefit plan or is otherwise subject to clinical review (including prior authorization), the following criteria will be used to determine whether the drug meets any applicable medical necessity requirements for the intended/prescribed purpose.

Spinraza (nusinersen)

Initial requests for Spinraza (nusinersen) may be approved if the following criteria are met:

1. Documentation is provided that individual has a diagnosis by either:
   • A. Spinal Muscular Atrophy (SMA) diagnostic test results verifying 0 copies of SMN1; OR
   • B. Molecular genetic testing of 5q SMA for any of the following:
     1. homozygous gene deletion; or
     2. homozygous conversion mutation; or
     3. compound heterozygote;
2. Documentation is provided that individual has either:
   • A. Genetic testing verifying no more than 2 copies of SMN2 (Finkel 2017); OR
   • B. Onset of SMA-associated signs and symptoms before 21 months of age (Mercuri 2018).
3. Individual does not require use of invasive ventilatory support (tracheotomy with positive pressure) or use of non-invasive ventilator support (BiPAP) for more than 16 hours per day as a result of advanced SMA disease.

Initial requests for Spinraza following treatment with Zolgensma (onasemnogene abeparvovec-xioi) may be approved if the following criteria are met:

1. When Spinraza therapy is determined to meet the above criteria; AND
2. Documentation is provided that individual has experienced a decline in clinical status (including but not limited to loss of motor milestone) since receipt of gene therapy.

Continuation requests for Spinraza (nusinersen) may be approved if the following criteria are met:

1. When initial therapy was determined to meet the above criteria; AND
2. Individual does not require use of invasive ventilatory support (tracheotomy with positive pressure) or use of non-invasive ventilator support (BiPAP) for more than 16 hours per day as a result of advanced SMA disease; AND
3. Documentation is provided that individual has clinically significant improvement in spinal muscular atrophy-associated signs and symptoms (i.e., progression, stabilization, or decreased decline in motor function) compared to the predicted natural history trajectory of disease.

Non-Approval Conditions

Requests for Spinraza (nusinersen) may not be approved for the following:

1. When the above criteria are not met and for all other indications; OR
2. When used in combination therapy with Evrysdi (risdiplam).

Approval Duration: Initial and continuation requests: 6 months

Quantity Limits

Spinraza (nusinersen) Quantity Limits: Spinraza (nusinersen) 12 mg/5 mL vial*

• 1 vial (12 mg) per 4 months
• *For initiation of therapy, may approve 4 loading doses of 12 mg (1 vial) each in the first 4 months of therapy

Override Criteria

Coding

The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy.

Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

CPT

• 96450

HCPCS

• J2326

ICD-10 Diagnosis

• G12.0
• G12.1

Chemotherapy administration, into CNS (eg, intrathecal), requiring and including spinal puncture [when associated with administration of nusinersen (SPINRAZA)]

Injection, nusinersen, 0.1 mg [SPINRAZA]

Infantile spinal muscular atrophy, type I (Werdnig-Hoffman)

Other inherited spinal muscular atrophy [includes types II, III (Kugelberg-Welander) and IV]

Document History

Revised: 11/17/2023