Medical Policy: 05.02.05 

Original Effective Date: March 2017 

Reviewed: May 2017 

Revised: May 2017 

 

Benefit Application:

Benefit determinations are based on the applicable contract language in effect at the time the services were rendered. Exclusions, limitations or exceptions may apply. Benefits may vary based on contract, and individual member benefits must be verified. Wellmark determines medical necessity only if the benefit exists and no contract exclusions are applicable. This medical policy may not apply to FEP. Benefits are determined by the Federal Employee Program.

 

This Medical Policy document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy will be reviewed regularly and be updated as scientific and medical literature becomes available.

 

Description:

The intent of the Spinraza policy is to encourage appropriate use according to clinical guidelines and/or clinical trials in the treatment of spinal muscular atrophy (SMA).

 

Spinraza (nusinersen) is an intrathecally administered antisense oligonucleotide that increases the amount of functional survival motor neuron (SMN) protein which is deficient in individuals diagnosed with SMA. SMA is a rare, and often fatal, genetic disease affecting muscle strength and movement.

 

Prior Approval:

 

Prior approval is required.

 

Policy:

Required Documentation

The following information is necessary to initiate the prior authorization review:

  • Deletion or mutation at the SMN1 allele confirmed by genetic testing

 

Criteria for Initial Approval

  1.  Spinraza (nusinersen) may be considered medically necessary for the treatment of spinal muscular atrophy (SMA) in patients who meet the following criteria:
    • Patient has a diagnosis of SMA confirmed by genetic testing showing deletion or mutation at the SMN1 allele
    • Patient has Type 1, Type 2 or Type 3 SMA
    • The diagnosis was made at or before 18 years of age
    • The medication must be prescribed by or in consultation with a neurologist or neuromuscular specialist
    • Patient is not dependent on either of the following:
      • Invasive ventilation or tracheostomy
      • Use of non-invasive ventilation beyond use for naps and nighttime sleep

 

Initial approval will be for 6 months.

 

 

  1. Spinraza (nusinersen) is considered investigational for patients with type 0 and IV spinal muscular atrophy.

 

 

Continuation of Therapy

 

  1. For continuation therapy, Spinraza (nusinersen) may be considered medically necessary for the treatment of spinal muscular atrophy (SMA) in patients who meet the following criteria:
    • Patient meets initial criteria for approval above
    • Patient is receiving a clinical benefit from Spinraza (nusinersen) therapy, as demonstrated by improvement or maintenance of motor skills or ability to sit, crawl, stand or walk, or new motor milestones

Approval will be for 12 months.

 

*Note: If an individual meets medically necessary criteria, dosing of nusinersen 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 the evaluation and demonstration of nusinersen's clinical effectiveness in the treated individual every 12 months.

 

 

CLINICAL RATIONALE

Infantile-Onset or Type I SMA

For individuals who have infantile-onset or type I SMA (symptomatic or presymptomatic) who receive Spinraza (nusinersen), the evidence includes 2 randomized, double-blind, controlled trials and 1 single-arm open-label study.  Relevant outcomes are disease-specific survival, change in disease status, morbid events, functional outcomes, health status measures, quality of life, and treatment-related mortality and morbidity. Trial results in symptomatic patients showed clinically meaningful improvement in motor milestones as well as event-free survival that exceeded those seen in the control group with an acceptable safety profile.  Proportion of patients, who met the primary endpoint responder definition of achieving motor milestones, was 40% in the Spinraza (nusinersen) arm compared to 0 in the sham-controlled arm.  Further, the hazard ratio for event-free survival was 0.53 in favor of Spinraza (nusinersen) versus sham controlled.  It is notable, however, that a majority of Spinraza (nusinersen) treated subjects did not achieve the primary endpoint motor milestone response.  Given the limited data on durability of response, long-term safety, and lack of efficacy in substantial number of patients, continued risk-benefit assessment of long-term treatment with nusinersen is necessary.  The open-label uncontrolled trial in presymptomatic infantile onset SMA patients found a benefit of early treatment with Spinraza (nusinersen).  The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

 

Type II and III SMA

For individuals with type II or III SMA who receive Spinraza (nusinersen), the evidence includes 4 single arm studies and 1 double-blind RCT.  Relevant outcomes are change in disease status, morbid events, functional outcomes, healthy status measures, quality of life, treatment-related mortality and treatment-related morbidity.  Efficacy from single arm studies is difficult to interpret because these trials used a wide range of Spinraza (nusinersen) doses, included both type II and III and lacked a control arm.  Results of the confirmatory phase III CHERISH trial were presented at the annual American Academy of Neurology (AAN) meeting in April 2017.  The study has shown that nusinersun is effective in the later-onset SMA children similarly to that observed in early-onset SMA children. In the data, it was noted that in more than 57% of the treated patients, Hammersmith Functional Motor Scale–Expanded (HFMSE) scores improved by 3 or more points at month 15, compared to about 20% of the controls. The trial reported a “favorable safety profile” with no withdrawals due to adverse events. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome. 

 

Type 0 and IV SMA

For individuals who have Type 0 or IV SMA who receive Spinraza (nusinersen), the evidence is lacking.  Relevant outcomes are change in disease status, morbid events, functional outcomes, health status measures, quality of life, treatment-related mortality and treatment-related morbidity.  The evidence is insufficient to determine the effects of technology on health outcomes.

 

Procedure Codes and Billing Guidelines:

To report provider services, use appropriate CPT* codes, Alpha Numeric (HCPCS level 2) codes, Revenue codes, and/or ICD Diagnostic Codes.

  • J3490, unclassified injection

 

Selected References:

  • Spinraza [package insert]. Cambridge, MA: Biogen Inc; 2016.
  • Finkel RS, Chiriboga CA, Vajsar J, et al. Treatment of infantile-onset spinal muscular atrophy with nusinersen: a phase 2, open-label, dose-escalation study. Lancet. 2017;388(10063):3017-26.
  • Chiriboga CA, Swoboda KJ, Darras BT, et al. results from a phase 1 study of nusinersen (ISIS-SMN(Rx)) in children with spinal muscular atrophy. Neurology. 2016;86(10):890-97.
  • National Institute for Health and Care Excellence. 2016. Proposed health technology appraisal. Accessed February 22, 2017.
  • Prior TW. Perspectives and diagnostic considerations in spinal musclular atrophy. Genet Med. 2010;12(3):145-52.
  • National Organization for Rare Disorders. Russman B. 2012. Accessed February 22, 2017.
  • Muscular Dystrophy Association. Spinal Muscle Atrophy. n.d.; Accessed February 22, 2017.
  • 2017 Blue Cross Blue Shield Association Spinraza policy (adopted March 2017).
  • Schneider E, Mignon L, Su J, et al. Nusinersen in Symptomatic Children with Later-onset Spinal Muscular Atrophy (SMA): Design of the Phase 3 CHERISH Study. Presented at the AAN 2017 Annual Meeting; Boston, MA; April 22-28, 2017. Abstract 184.
  • Mercuri E, Finkel R, Kirschner J, et al.  Efficacy and safety of nusinersen in children with later-onset spinal muscular atrophy (SMA): interim results of the phase 3 CHERISH study. Presented at the AAN 2017 Annual Meeting; Boston, MA; April 22-28, 2017.

 

Policy History:

  • May 2017 - Interim Review, PolicyRevised
  • March 2017 - New policy

Wellmark medical policies address the complex issue of technology assessment of new and emerging treatments, devices, drugs, etc.   They are developed to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. Wellmark medical policies contain only a partial, general description of plan or program benefits and do not constitute a contract. Wellmark does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Wellmark or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. Our medical policies may be updated and therefore are subject to change without notice.

 

*CPT® is a registered trademark of the American Medical Association.