Pharmacy Prior Authorization Criteria

Evrysdi (risdiplam)

Indications for Prior Authorization

Evrysdi (risdiplam)

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

Criteria

Evrysdi

*Baseline assessments for patients less than 2 months of age requesting risdiplam 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: 12 Months
For diagnosis of Spinal Muscular Atrophy

• Diagnosis of spinal muscular atrophy (SMA) Type I, II, or III [1-3, A]
AND
• Both of the following: [1-7]
• The mutation or deletion of genes in chromosome 5q resulting in one of the following: [B]
• 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 [C]
AND
• Patient is not dependent on invasive ventilation or tracheostomy [2-3, D]
AND
• Patient is not dependent on the use of non-invasive ventilation beyond use for naps and nighttime sleep [3, D]
AND
• At least one of the following exams (based on patient age and motor ability) has been conducted to establish baseline motor ability*: [2-7, E]
• Hammersmith Infant Neurological Exam Part 2 (HINE-2) (infant to early childhood)
• Hammersmith Functional Motor Scale Expanded (HFMSE)
• Revised Upper Limb Module (RULM) Test (Non ambulatory)
• Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND)
• Motor Function Measure 32 (MFM-32) Scale
• Item 22 of the Bayley Scales of Infant and Toddler Development Third Edition (BSID-III)
AND
• Prescribed by or in consultation with a neurologist with expertise in the diagnosis and treatment of SMA
AND
• Patient is not to receive concomitant chronic survival motor neuron (SMN) modifying therapy for the treatment of SMA (e.g., Spinraza) [2-3, 10, F]
AND
• One of the following: [2-3, 10, 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 inadequate response to gene therapy (e.g., sustained decrease in at least one motor test score over a period of 6 months)

Evrysdi

Prior Authorization (Reauthorization)

Length of Approval: 12 Months
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 previous improvement in more HINE motor milestones than worsening, from pretreatment baseline (net positive improvement)
• Patient has achieved and maintained any new motor milestones when they would otherwise be unexpected to do so (e.g., sit unassisted, stand, walk)
OR
• One of the following HFMSE milestones: [8]
• 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 RULM test milestones: [2, 8-9]
• 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]
• 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)
OR
• One of the following MFM-32 milestones: [2]
• 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
• Improvement in the ability to sit without support for at least 5 seconds as assessed by item 22 of the Gross Motor Scale of the Bayley Scales of Infant and Toddler Development Third Edition (BSID-III) [2-3]
AND
• Patient continues to not be dependent on invasive ventilation or tracheostomy [2-3, D]
AND
• Patient continues to not be dependent on the use of non-invasive ventilation beyond use for naps and nighttime sleep [3, D]
AND
• Prescribed by or in consultation with a neurologist with expertise in the diagnosis and treatment of SMA
AND
• Patient is not to receive concomitant chronic survival motor neuron (SMN) modifying therapy for the treatment of SMA (e.g., Spinraza) [2-3, 10, F]
AND
• One of the following: [2-3, 10, 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 inadequate response to gene therapy (e.g., sustained decrease in at least one motor test score over a period of 6 months)

P & T Revisions

2024-10-18, 2024-10-03, 2023-10-12, 2022-10-07, 2022-07-06, 2022-06-16, 2021-10-07, 2021-05-25, 2020-11-30

References

1. Evrysdi prescribing information. Genentech, Inc. South San Francisco, CA. September 2024.
2. Day JW, Annoussamy M, Baranello G, et al. SUNFISH Part 2: 24-month efficacy outcomes of risdiplam (RG7916) treatment in patients with Type 2 or 3 spinal muscular atrophy (SMA). Presented at the 2020 Virtual SMA Research & Clinical Care Meeting. June 12, 2020.
3. Servais L, Baranello G, Masson R, et al. FIREFISH Part 2: Efficacy and safety of risdiplam (RG7916) in infants with Type 1 spinal muscular atrophy (SMA). Presented at the 2020 Virtual SMA Research & Clinical Care Meeting. June 12, 2020.
4. Markowitz JA, Sing P, Darras BT. Spinal muscular atrophy: a clinical and research update. Pediatr Neurol. 2012;46(1):1-12.
5. 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.
6. Bertini E DJ, Muhaizea A, et al. RAINBOWFISH: A Study of Risdiplam (RG7916) in Newborns with Presymptomatic Spinal Muscular Atrophy. Presented at: World Muscle Society; October 1–5, 2019; Copenhagen, Denmark.
7. 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.
8. 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.
9. 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.
10. 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
11. Evrysdi [AMCP dossier]; South San Francisco, CA: Genentech; September 2020.

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End Notes

1. There were two major Phase 2/3 trials that the FDA assessed when determining Evrysdi’s clinical efficacy and subsequent approval (SUNFISH and FIREFISH). SUNFISH only enrolled patients with SMA Types 2 and 3 and FIREFISH only enrolled patients with SMA Type 1. [2-3]
2. This is the definition that the clinical trials SUNFISH and FIREFISH used. Also consistent with clinical guidelines. [2-7]
3. FIREFISH required patients to have 2 copies of SMN2, and SUNFISH only enrolled patients with 2-4 copies of SMN2. [2-3]
4. Invasive ventilation or tracheostomy was an exclusion criteria in both the SUNFISH and FIREFISH trials. Use of non-invasive ventilation beyond use for naps and nighttime sleep was only an exclusion criteria in FIREFISH. [2-3]
5. MFM-32 was included in Evrysdi criteria but not Spinraza because Spinraza did not study MFM-32 as an endpoint. Baseline motor score standards was only used as an inclusion criterion for SUNFISH. Revised upper limb module (RULM) entry item A (Brooke score) equal to or greater than 2 AND MFM-32 (Item 9) scores equal to or greater than 1 were required. As this was only for the SUNFISH trial and only applied to some of the motor scores, it was deemed unnecessary to include as a criterion. [2]
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., Evrysdi and Zolgensma) is superior to any single treatment alone. Both FIREFISH and SUNFISH excluded patients that were on concomitant or previous treatment with either SMN2-targeting antisense oligonucleotide, or gene therapy (e.g., Spinraza or Zolgensma). JEWELFISH is an ongoing open label phase 2 trial that included patients previously treated with another SMA targeted therapy (e.g., Zolgensma, Spinraza). JEWELFISH is scheduled to be completed in January 2025. [2-3,10-11]

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Revision History

• 2024-10-18: 2024 Annual Review. No criteria changes. Updated references.
• 2024-10-03: 2024 Annual Review. No criteria changes. Updated references.
• 2023-10-12: Program update to standard reauthorization language. No changes to clinical intent.
• 2022-10-07: Update Guideline
• 2022-07-06: Updated to remove age requirement per FDA expanded indication
• 2022-06-16: Removed submission of medical records and/or paid claims requirement from prior authorization criteria
• 2021-10-07: Annual review
• 2021-05-25: Addition of EHB formulary. No changes to criteria
• 2020-11-30: Updates for December 2020 P&T

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