WHA

Zolgensma (onasemnogene abeparvovec-xioi) - PA, NF

Indications for Prior Authorization

Zolgensma (onasemnogene abeparvovec-xioi)
  • For diagnosis of Spinal Muscular Atrophy (SMA)
    Indicated for the treatment of pediatric patients less than 2 years of age with spinal muscular atrophy (SMA) with bi-allelic mutations in the survival motor neuron 1 (SMN1) gene.

    Limitation of Use: • The safety and effectiveness of repeat administration of ZOLGENSMA have not been evaluated. • The use of ZOLGENSMA in patients with advanced SMA (e.g., complete paralysis of limbs, permanent ventilator dependence) has not been evaluated.

Criteria

Zolgensma

Prior Authorization

Length of Approval: 1 Time Authorization in Lifetime

  • The mutation or deletion of genes in chromosome 5q resulting in one of the following: [1-8, A]
    • Homozygous gene deletion or mutation of SMN1 gene (e.g., homozygous deletion of exon 7 at locus 5q13)
      • OR
    • Compound heterozygous mutation of SMN1 gene (e.g., deletion of Survival of Motor Neuron 1 [SMN1] exon 7 [allele 1] and mutation of SMN1 [allele 2])
    AND
  • One of the following:
    • Both of the following: [1-5]
      • Diagnosis of symptomatic spinal muscular atrophy (SMA) confirmed by a neurologist with expertise in the diagnosis and treatment of SMA [B]
        • AND
      • Patient is less than or equal to 2 years of age
      OR
    • All of the following:
      • Diagnosis of SMA based on the results of SMA newborn screening
        • AND
      • Patient has 4 copies or less of Survival of Motor Neuron 2 (SMN 2)
        • AND
      • Patient is less than or equal to 6 months of age [2-5]
    AND
  • Patient is not dependent on invasive ventilation or tracheostomy [2-5, C]
    • AND
  • Patient is not dependent on the use of non-invasive ventilation beyond use for naps and nighttime sleep [2-5, C]
    • AND
  • Documentation of anti-AAV9 antibody titers being less than or equal to 1:50 [1]
    • AND
  • Patient is not to receive concomitant chronic survivor motor neuron (SMN) modifying therapy for the treatment of SMA (e.g. Spinraza, Evrysdi) [2-5,D]
    • AND
  • Prescribed by a neurologist with expertise in the diagnosis and treatment of SMA
    • AND
  • Patient has never received Zolgensma treatment in their lifetime [1]
Zolgensma

Non Formulary

Length of Approval: 1 Time Authorization in Lifetime

  • Submission of medical records (e.g., chart notes) documenting the mutation or deletion of genes in chromosome 5q resulting in one of the following: [1-8, A]
    • Homozygous gene deletion or mutation of SMN1 gene (e.g., homozygous deletion of exon 7 at locus 5q13)
      • OR
    • Compound heterozygous mutation of SMN1 gene (e.g., deletion of Survival of Motor Neuron 1 [SMN1] exon 7 [allele 1] and mutation of SMN1 [allele 2])
    AND
  • One of the following:
    • Both of the following: [1-5]
      • Diagnosis of symptomatic spinal muscular atrophy (SMA) confirmed by a neurologist with expertise in the diagnosis and treatment of SMA [B]
        • AND
      • Patient is less than or equal to 2 years of age
      OR
    • All of the following:
      • Diagnosis of SMA based on the results of SMA newborn screening
        • AND
      • Patient has 4 copies or less of Survival of Motor Neuron 2 (SMN 2)
        • AND
      • Patient is less than or equal to 6 months of age [2-5]
    AND
  • Patient is not dependent on invasive ventilation or tracheostomy [2-5, C]
    • AND
  • Patient is not dependent on the use of non-invasive ventilation beyond use for naps and nighttime sleep [2-5, C]
    • AND
  • Submission of medical records (e.g., chart notes) documenting anti-AAV9 antibody titers being less than or equal to 1:50 [1]
    • AND
  • Patient is not to receive concomitant chronic survivor motor neuron (SMN) modifying therapy for the treatment of SMA (e.g. Spinraza, Evrysdi) [2-5,D]
    • AND
  • Prescribed by a neurologist with expertise in the diagnosis and treatment of SMA
    • AND
  • Patient has never received Zolgensma treatment in their lifetime [1]

  • Guideline ID
    GL-147636

  • Formulary
    premium

  • Effective date
    Aug 1, 2024

  • P&T approval date

P & T Revisions

2024-06-05, 2023-06-19, 2022-11-29, 2022-06-16, 2021-06-07, 2021-04-20, 2020-11-20, 2020-06-19

  1. Zolgensma Prescribing Information. AveXis Inc. Bannockburn, IL. October 2023.
  2. Mendell J.R., Al-Zaidy S, Shell R, etc. Single-Dose Gene Replacement Therapy for Spinal Muscular Atrophy. New Eng J of Med. 2017; 377:1713-22.
  3. Al-Zaidy S, Pickard AS, Kotha K, et al. Health outcomes in spinal muscular atrophy type 1 following AVXS-101 gene replacement therapy. Pediatr Pulmonol. 2019;54(2):179-185.
  4. Day JW, Chiriboga CA, Crawford TO, et al. AVXS-101 gene-replacement therapy for spinal muscular atrophy type 1: phase 3 study (STR1VE) update. Poster presented at: The 71st Annual American Academy of Neurology Meeting, Philadelphia PA, May 4-10, 2019.
  5. Strauss KA, Swoboda KJ, Farrar MA, et al. AVXS-101 gene-replacement therapy in presymptomatic spinal muscular atrophy: SPR1NT study update. Poster presented at the 71st Annual American Academy of Neurology Meeting; May 4-10; 2019; Philadelphia, PA.
  6. Markowitz JA, Sing P, Darras BT. Spinal muscular atrophy: a clinical and research update. Pediatr Neurol. 2012;46(1):1-12.
  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. 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.
  9. 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.
  10. 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. This is the definition that the clinical trials used. Also consistent with clinical guidelines. [2-8]
  2. There were 3 key clinical trials for Zolgensma (START, STR1VE, SPR1NT). START and STR1VE only enrolled patients with SMA Type 1 and SPR1NT enrolled pre-symptomatic SMA patients. [2-5]
  3. Exclusion criteria found in clinical trials. [2-5]
  4. 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 Zolgensma) is superior to any single treatment alone. RESPOND is a phase 4 trial 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. [9-10]
  • 2024-06-05: 2024 Annual Review. No criteria changes. Updated references.
  • 2023-06-19: Annual Review
  • 2022-11-29: update guideline
  • 2022-06-16: Annual review - removed submission of medical records requirement from prior authorization criteria. Updated references.
  • 2021-06-07: Annual Review
  • 2021-04-20: Updated guideline
  • 2020-11-20: Annual Review Updates
  • 2020-06-19: Annual review