Clinical Policy: Nusinersen (Spinraza)

Reference Number: CP.PHAR.327
Effective Date: 03.01.17
Last Review Date: 05.26
Line of Business: Commercial, HIM/ICHRA, Medicaid

[Coding Implications](Coding Implications)
[Revision Log](Revision Log)

See [Important Reminder](Important Reminder) at the end of this policy for important regulatory and legal information.

Description

Nusinersen (Spinraza®) is a survival motor neuron-2 (SMN2)-directed antisense oligonucleotide.

FDA Approved Indication(s)

Spinraza is indicated for the treatment of spinal muscular atrophy (SMA) in pediatric and adult patients.

Policy/Criteria

a. Provider must submit evidence of poor response to Zolgensma or Itvisma (e.g., sustained decrease in CHOP-INTEND or HFMSE score over a period of at least 6 months);  
b. Documentation of provider attestation of clinical deterioration;

11. Total dose does not exceed one of the following (a or b):
    a. Low dose regimen: 4 doses of 12 mg prescribed for intrathecal use;
    b. High dose regimen: 2 doses of 50 mg prescribed for intrathecal use.

Approval duration: 12 months (up to 4 doses)

B. Other diagnoses/indications (must meet 1 or 2):

1. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b):
   a. For drugs on the formulary (commercial, health insurance marketplace/ICHRA) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace/ICHRA, and CP.PMN.255 for Medicaid; or
   b. For drugs NOT on the formulary (commercial, health insurance marketplace/ICHRA) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace/ICHRA, and CP.PMN.16 for Medicaid; or
2. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace/ICHRA, and CP.PMN.53 for Medicaid.

II. Continued Therapy

A. Spinal Muscular Atrophy (must meet all):

     1) For HFMSE, RHS, ULM or RULM, must demonstrate score improvement or maintenance of previous score improvement from baseline score submitted at first renewal since turning 2 years old;  
     2) For 6MWT distance, must demonstrate improvement or maintenance of baseline distance;  
  iii. If > 2 years at therapy initiation, must meet one of the following (1, 2, 3, or 4) (see Appendix D):  
     1) For HFMSE or RHS, must demonstrate score improvement or maintenance of previous score improvement of ≥ 3 points from baseline;  
     2) For ULM, must demonstrate score improvement or maintenance of previous improvements in ≥ 2 points from baseline;  
     3) For RULM, must demonstrate score improvement or maintenance of previous improvements in ≥ 4 points from baseline;  
     4) For 6MWT distance, must demonstrate improvement or maintenance of baseline distance;

c. Member has not had a decline in motor function test score(s) from baseline AND medical justification demonstrates and supports that member is responding positively to therapy;

4. Spinraza is not prescribed concurrently with Evrysdi, Itvisma, or Zolgensma;
5. If request is for a dose increase, new dose does not exceed one of the following (a, b, or c, see Appendix D):
   a. Low dose regimen: 12 mg every 4 months prescribed for intrathecal use;
   b. High dose regimen: 28 mg every 4 months prescribed for intrathecal use;
   c. If transitioning from low dose regimen to high dose regimen: 50 mg once, followed by 28 mg every 4 months prescribed for intrathecal use.

Approval duration: 12 months

B. Other diagnoses/indications (must meet 1 or 2):

1. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b):

CLINICAL POLICY

Nusinersen

a. For drugs on the formulary (commercial, health insurance marketplace/ICHRA) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace/ICHRA, and CP.PMN.255 for Medicaid; or
b. For drugs NOT on the formulary (commercial, health insurance marketplace/ICHRA) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace/ICHRA, and CP.PMN.16 for Medicaid; or

2. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace/ICHRA, and CP.PMN.53 for Medicaid.

III. Diagnoses/Indications for which coverage is NOT authorized:

A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off label use policies – CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace/ICHRA, and CP.PMN.53 for Medicaid, or evidence of coverage documents.

IV. Appendices/General Information

Appendix A: Abbreviation/Acronym Key

CHOP-INTEND: Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorder
FDA: Food and Drug Administration
HFMSE: Hammersmith functional motor scale expanded
HINE: Hammersmith Infant Neurological Examination
RHS: Revised Hammersmith Scale
RULM: Revised Upper Limb Module
SMA: spinal muscular atrophy
SMN: survival motor neuron
ULM: Upper Limb Module
6MWT: 6-Minute Walk Test

Appendix B: Therapeutic Alternatives

This table provides a listing of preferred alternative therapy recommended in the approval criteria. The drugs listed here may not be a formulary agent for all relevant lines of business and may require prior authorization.

Therapeutic alternatives are listed as Brand name® (generic) when the drug is available by brand name only and generic (Brand name®) when the drug is available by both brand and generic.

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Nusinersen

Appendix C: Contraindications/Boxed Warnings

None reported

Appendix D: General Information

• SMA is an autosomal recessive genetic disorder. It is caused by mutations in the SMN1 (survival motor neuron) gene that is found on chromosome 5 (hence the name 5q-SMA). To develop SMA, an individual must inherit two faulty (deletion or mutation) SMN1 genes, one from each parent.
• There are other types of SMA that are not related to chromosome 5 or SMN. Safety and efficacy of Spinraza in non-SMN-related SMA have not been established.
• SMN-related SMA is classified as type 1 through 4 depending on time of onset. The age of disease onset of symptoms correlates with disease severity: the earlier the age of onset, the greater the impact on motor function. Children who display symptoms at birth or in infancy typically have the lowest level of functioning (type 1). SMA onset in children (types 2 and 3), teens or adults (type 4) generally correlates with increasingly higher levels of motor function.
• Efficacy of Spinraza was established primarily in infantile disease (SMA type 1). Spinraza was approved based on interim results of an unpublished Phase III study of patients with spinal muscular atrophy type I (infantile-onset). The phase III study, referred to as ENDEAR, enrolled infants diagnosed with symptomatic, genetically confirmed spinal muscular atrophy (SMA) type I with two copies of SMN2 gene. Key inclusion criteria were: genetic documentation of 5q SMA homozygous gene deletion, homozygous mutation or compound heterozygote, onset of clinical signs and symptoms consistent with SMA at ≤ 6 months, at study entry, receiving adequate nutrition and hydration) with or without gastrostomy), seven month of age or younger at screening, body weight ≥ 3rd percentile for age, gestational age of 37 to 42 weeks. Key exclusion criteria were: Hypoxemia and signs or symptoms of SMA present at birth within the 1st week after birth
• Based on the mechanism of action of Spinraza, SMN2 must be present in sufficient amount for the production of full length SMN protein required to alleviate or minimize the symptoms of SMA.
• All subjects in the ENDEAR study had at least 2 copies of SMN2 genes (98% of the subjects in the pivotal study had 2 copies of SMN2 genes, while other 3 or 4 copies).
• It is unknown whether patients with less than 2 copies would make sufficient SMN protein to mitigate the symptoms of SMA as the efficacy of this agent has not been demonstrated in patients with less than 2 copies of SMN 2 genes.
• SMN2 gene copy and SMA types
  
  • SMN2 gene copy numbers are variable in individuals with spinal muscular atrophy. Higher numbers typically correlate with less severe disease.
  • More than 95% of individuals with spinal muscular atrophy retain at least 1 copy of the SMN2 gene
  • About 80% of individuals with Type I spinal muscular atrophy have 1 or 2 copies of the SMN2 gene
  • About 82% of individuals with Type II spinal muscular atrophy have 3 copies of the SMN2 gene

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Nusinersen

• About 96% of individuals with Type III spinal muscular atrophy have 3 or 4 copies of the SMN2 gene
• The CHOP-INTEND score is a validated 16-item, 64-point scale shown to be reliable and sensitive to change over time for SMA Type 1. In a prospective cohort study of SMA type I patients (n = 34), the mean rate of decline in the CHOP-INTEND score was 1.27 points/year (95% CI 0.21-2.33, p = 0.02).
• The HINE Section 2 motor milestone exam is an easily performed and relatively brief standardized clinical neurological examination that is optimal for infants aged between 2 and 24 months with good inter-observer reliability. This endpoint evaluates seven different areas of motor milestone development, with a maximum score between 2-4 points for each, depending on the milestone, and a total maximum score of 26 points.
• The HFSME score combines the Hammersmith Functional Motor Scale with a 13-item expansion module for ability to distinguish motor skills among individuals who may be older or with SMA types II and III. Each item is graded from 0 to 3, with 0 signifying no response, with a total of 66 points. HFMSE has demonstrated reliability and validity in patients with SMA. An increase of greater than 2 points in total score is unlikely in untreated SMA.
• The RHS is an ordinal scale which consists of 33 items with grades of 0, 1, and 2. Individuals who can achieve the task without any compensation are given a score of 2. Those who only attempt the movement or finish it with some form of compensation are given a score of 1. A score of 0 is given when patients are unable to perform any part of the item. The total maximum score is 69 points.
• The RULM is a set of 19 tasks that measure motor function in non-ambulatory SMA patients. Each task is assessed with a 3 point ordinal scale, with a total maximum score of 37 points. Meanwhile, the maximum score for ULM was 18.
• The 6MWT is a clinical outcome measure for ambulatory SMA that has been determined to be functionally meaningful and capable of capturing disease severity.
• Per the 2025 AAN SMA update, when considering a medication or treatment plan change, unless there is an URGENT indication, a medication and associated patient outcomes should be monitored for a minimum of 6-12 months before making a change (89% agreement).
  
  • URGENT indications to consider changing a treatment plan outside of a 6-12 months assessment period (100% agreement) include:
    
    • Significant side effects or intolerance to medication not acceptable to the patient or health care provider
    • Intolerance to medication administration route
    • Significant disease progression as determined by the health care provider and patient/caregiver
    • Loss of motor milestones (infancy and young child)

V. Dosage and Administration

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Nusinersen

VI. Product Availability

Single-dose vials for intrathecal injection: 12 mg/5 mL (2.4 mg/mL), 28 mg/5 mL (5.6 mg/mL), 50 mg/5 mL (10 mg/mL)

Coding Implications

Codes referenced in this clinical policy are for informational purposes only. Inclusion or exclusion of any codes does not guarantee coverage. Providers should reference the most up-to-date sources of professional coding guidance prior to the submission of claims for reimbursement of covered services.

Reviews, Revisions, and Approvals

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Nusinersen

Important Reminder

This clinical policy has been developed by appropriately experienced and licensed health care professionals based on a review and consideration of currently available generally accepted standards of medical practice; peer-reviewed medical literature; government agency/program approval status; evidence-based guidelines and positions of leading national health professional organizations; views of physicians practicing in relevant clinical areas affected by this clinical policy; and other available clinical information. The Health Plan makes no representations and accepts no liability with respect to the content of any external information used or relied upon in developing this clinical policy. This clinical policy is consistent with standards of medical practice current at the time that this clinical policy was approved. “Health Plan” means a health plan that has adopted this clinical policy and that is operated or administered, in whole or in part, by Centene Management Company, LLC, or any of such health plan’s affiliates, as applicable.