WHA

Spinraza (nusinersen)

Indications for Prior Authorization

Spinraza (nusinersen)
  • For diagnosis of Spinal Muscular Atrophy
    Indicated for the treatment of spinal muscular atrophy (SMA) in pediatric and adult patients.

Criteria

Spinraza

*Baseline assessments for patients less than 2 months of age requesting nusinersen proactively are not necessary in order to not delay access to initial therapy in recently diagnosed infants. Initial assessments shortly post-therapy can serve as baseline with respect to efficacy reauthorization assessment.

Prior Authorization (Initial Authorization)

Length of Approval: 3 Months [A]
For diagnosis of Spinal Muscular Atrophy

  • Diagnosis of spinal muscular atrophy (SMA) Type I, II, or III [1-4, B]
    • AND
  • Both of the following: [1-7]
    • The mutation or deletion of genes in chromosome 5q resulting in one of the following: [C]
      • Homozygous gene deletion or mutation (e.g., homozygous deletion of exon 7 at locus 5q13)
        • OR
      • Compound heterozygous mutation (e.g., deletion of SMN1 exon 7 [allele 1] and mutation of SMN1 [allele 2])
      AND
    • Patient has at least 2 copies of SMN2 [D]
    AND
  • Patient is not dependent on invasive ventilation or tracheostomy [2-4, E]
    • AND
  • Patient is not dependent on the use of non-invasive ventilation beyond use for naps and nighttime sleep [2-4, E]
    • AND
  • At least one of the following exams (based on patient age and motor ability) has been conducted to establish baseline motor ability*: [2-10]
    • Hammersmith Infant Neurological Exam (HINE) (infant to early childhood)
    • Hammersmith Functional Motor Scale Expanded (HFMSE)
    • Upper Limb Module (ULM) Test (Non ambulatory)
    • Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND)
    AND
  • Prescribed by or in consultation with a neurologist with expertise in the diagnosis and treatment of SMA
    • AND
  • Spinraza is to be administered intrathecally by, or under the direction of, healthcare professionals experienced in performing lumbar punctures [1]
    • AND
  • Patient is not to receive concomitant chronic survival motor neuron (SMN) modifying therapy for the treatment of SMA (e.g., Evrysdi) [2-4, F]
    • AND
  • One of the following: [2-4, 11, F]
    • Patient has not previously received gene replacement therapy for the treatment of SMA (e.g., Zolgensma)
      • OR
    • Both of the following:
      • Patient has previously received gene therapy for the treatment of SMA (e.g., Zolgensma)
      • Documentation of an inadequate response to gene therapy (e.g., sustained decrease in at least one motor test score over a period of 6 months)
    AND
  • Trial and failure or intolerance to Evrysdi
Spinraza

Prior Authorization (Reauthorization)

Length of Approval: 12 Months [A]
For diagnosis of Spinal Muscular Atrophy

  • Patient demonstrates positive clinical response to therapy from pretreatment baseline status as demonstrated by the most recent results from one of the following exams:
    • One of the following HINE-2 milestones: [2]
      • Improvement or maintenance of previous improvement of at least a 2 point (or maximal score) increase in ability to kick
      • Improvement or maintenance of previous improvement of at least a 1 point increase in any other HINE-2 milestone (e.g., head control, rolling, sitting, crawling, etc.), excluding voluntary grasp
      • Patient exhibited improvement, or maintenance of a previous improvement in more HINE motor milestones than worsening, from pretreatment baseline (net positive improvement)
      • Patient has achieved and maintained any new motor milestones from pretreatment baseline when they would otherwise be unexpected to do so (e.g., sit unassisted, stand, walk)
      OR
    • One of the following HFMSE milestones: [3, 9-10]
      • Improvement or maintenance of a previous improvement of at least a 3 point increase in score from pretreatment baseline
      • Patient has achieved and maintained any new motor milestone from pretreatment baseline when they would otherwise be unexpected to do so (e.g., sit unassisted, stand, walk)
      OR
    • One of the following ULM test milestones: [3, 12-13]
      • Improvement or maintenance of a previous improvement of at least a 2 point increase in score from pretreatment baseline
      • Patient has achieved and maintained any new motor milestone from pretreatment baseline when they would otherwise be unexpected to do so (e.g., sit unassisted, stand, walk)
      OR
    • One of the following CHOP INTEND milestones: [2, 4]
      • Improvement or maintenance of a previous improvement of at least a 4 point increase in score from pretreatment baseline
      • Patient has achieved and maintained any new motor milestone from pretreatment baseline when they would otherwise be unexpected to do so (e.g., sit unassisted, stand, walk)
    AND
  • Patient continues to not be dependent on invasive ventilation or tracheostomy [2-4, E]
    • AND
  • Patient continues to not be dependent on the use of non-invasive ventilation beyond use for naps and nighttime sleep [2-4, E]
    • AND
  • Prescribed by or in consultation with a neurologist with expertise in the diagnosis and treatment of SMA
    • AND
  • Spinraza is to be administered intrathecally by, or under the direction of, healthcare professionals experienced in performing lumbar punctures [1]
    • AND
  • Patient is not to receive concomitant chronic survival motor neuron (SMN) modifying therapy for the treatment of SMA (e.g., Evrysdi) [2-4, F]
    • AND
  • One of the following: [2-4, 11, F]
    • Patient has not previously received gene replacement therapy for the treatment of SMA (e.g., Zolgensma)
      • OR
    • Both of the following:
      • Patient has previously received gene therapy for the treatment of SMA (e.g., Zolgensma)
      • Documentation of an inadequate response to gene therapy (e.g., sustained decrease in at least one motor test score over a period of 6 months)
    AND
  • Trial and failure or intolerance to Evrysdi

  • Guideline ID
    GL-148133

  • Formulary
    Premium

  • Effective date
    Aug 1, 2024

  • P&T approval date

P & T Revisions

2024-06-21, 2023-10-04, 2023-06-19, 2022-06-16, 2021-06-01, 2020-11-30, 2020-11-20, 2020-06-02, 2020-01-09, 2019-07-22, 2019-07-02

  1. Spinraza Prescribing Information. Biogen, Inc. Cambridge, MA. April 2024.
  2. Finkel RS, Mercuri E, Darras, BT, et al. Nusinersen versus Sham Control in Infantile-Onset Spinal Muscular Atrophy. N Engl J Med. 2017; 377:1723-1732.
  3. Mercuri E, Darras BT, Chiriboga CA, et al. Nusinersen versus sham control in later-onset spinal muscular atrophy. N Engl J Med. 2018;378:625-635.
  4. De Vivo DC, Bertini E, Swoboda KJ, et al. Nusinersen initiated in infants during the pre-symptomatic stage of spinal muscular atrophy: Interim efficacy and safety results from the Phase 2 NURTURE study. Neuromuscul Disord. 2019;29(11):P842-856.
  5. Markowitz JA, Sing P, Darras BT. Spinal muscular atrophy: a clinical and research update. Pediatr Neurol. 2012;46(1):1-12.
  6. Mercuri E, Finkel RS, Muntoni F, et al. Diagnosis and management of spinal muscular atrophy: Part 1: Recommendations for diagnosis, rehabilitation, orthopedic and nutritional care. J Neuromuscul Dis. 2018;28(2):103-115.
  7. Wang CH, Finkel RS, Bertini ES, et al. Consensus statement for standard of care in spinal muscular atrophy. J Child Neurol. 2007;22(8):1027-1049.
  8. Haataja L, Mercuri E, Regev R, et al. Optimality score for the neurologic examination of the infant at 12 and 18 months of age. J Pediatr. 1999 Aug;135(2 Pt 1):153-61.
  9. Glanzman AM, O'Hagen JM, McDermott MP, et al. Validation of the Expanded Hammersmith Functional Motor Scale in spinal muscular atrophy type II and III. J Child Neurol. 2011;26(12):1499-507.
  10. O'Hagen JM, Glanzman AM, McDermott MP, et al. An expanded version of the Hammersmith Functional Motor Scale for SMA II and III patients. Neuromuscular disorders : NMD. 2007;17(9-10):693-7.
  11. Kirschner J, Butoianu N, Goemans N, et al. European ad-hoc consensus statement on gene replacement therapy for spinal muscular atrophy. Eur J Paediatr Neurol. 2020. https://doi.org/10.1016/j.ejpn.2020.07.001.
  12. Pera , M., Coratti, G., Mazzone, E., et al. (2019). Revised upper limb module for spinal muscular atrophy: 12 month changes. Muscle Nerve. Apr;59(4):426-430.
  13. Stolte B, Bois JM, Kizina K, et al. Minimal clinically important differences in functional motor scores in adults with spinal muscular atrophy. Eur. J. Neurol. 2020; 0:1-9.
  14. Biogen. Biogen plans to initiate phase 4 study evaluating benefit of Spinraza® (nusinersen) in patients treated with Zolgensma® (onasemnogene abeparvovec). https://investors.biogen.com/news-releases/news-release-details/biogen-plans-initiate-phase-4-study-evaluating-benefit-spinrazar. July 21, 2020. Accessed October 6, 2020.
  1. Spinraza is for intrathecal use only. Treatment is initiated with 4 loading doses; the first 3 loading doses should be administered at 14-day intervals, and the 4th loading dose should be administered 30 days after the 3rd loading dose. A maintenance dose should be administered once every 4 months thereafter. If a loading dose is delayed or missed, Spinraza should be administered as soon as possible, with at least 14 days between doses. If a maintenance dose is delayed or missed, Spinraza should be administered as soon as possible with continued dosing every 4 months. [1]
  2. There were 3 key pivotal trials demonstrating safety and efficacy of Spinraza (ENDEAR, CHERISH, NURTURE). ENDEAR enrolled patients with infantile-onset SMA (defined by the study as individuals diagnosed with 5q SMA and symptom onset at younger than 6 months of age), also known as SMA Type 1. CHERISH enrolled patients with later-onset SMA (defined by the study as individuals diagnosed with 5q SMA and symptom onset after 6 months of age), generally considered as SMA Type 2 or 3. NURTURE only enrolled patients with a diagnosis of 5q SMA who were ≤6 weeks old at first dose of Spinraza. This would be considered SMA Type 1. [2-4]
  3. This is the definition that the clinical trials ENDEAR, CHERISH, and NURTURE used. Also consistent with clinical guidelines. [2-7]
  4. ENDEAR required patients to have 2 copies of SMN2, CHERISH included patients with 2 to 4 copies of SMN2, and NURTURE only enrolled patients with 2 or 3 copies of SMN2. [2-4]
  5. Invasive ventilation or tracheostomy was an exclusion criteria in the ENDEAR, CHERISH, and NURTURE trials. [2-4]
  6. A recent European ad-hoc consensus statement on SMA stated that there currently is no published evidence that the combination of two disease modifying therapies (e.g., Spinraza and Evrysdi) is superior to any single treatment alone. Both ENDEAR, CHERISH, and NURTURE excluded patients that were had previous treatment with either gene therapy or prior antisense oligonucleotide (ASO) treatment (e.g., Zolgensma). RESPOND is a phase 4 clinical study that will assess the efficacy and safety of Spinraza in patients with suboptimal clinical response to Zolgensma. It is planned to begin enrollment in 2021. [2-4, 11, 14]
  • 2024-06-21: 2024 Annual Review. Removed bypass of Evrysdi trial requirement for patients younger than 2 months. Added Evrysdi trial requirement to reauthorization criteria. Background updates.
  • 2023-10-04: Program update to standard reauthorization language. No changes to clinical intent
  • 2023-06-19: Annual review
  • 2022-06-16: Annual review - removed submission of medical records requirement from prior authorization criteria.
  • 2021-06-01: 2021 Annual Review
  • 2020-11-30: Updates for December 2020 P&T
  • 2020-11-20: Annual Review Updates
  • 2020-06-02: Annual Review
  • 2020-01-09: update gpi
  • 2019-07-22: Updated guideline to include "Patient is not to receive concomitant gene therapy (e.g, Zolgensma)" within the reauthorization section as well
  • 2019-07-02: Updated Spinraza guideline to include the following "Patient is not to receive concomitant gene therapy (e.g, Zolgensma)" to align with newly developed Zolgensma guideline.