EVRYDSI (risdiplam)

Self-Administration – oral solution

Diagnosis considered for coverage:

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

Coverage Criteria:

For diagnosis of Spinal Muscular Atrophy (SMA):

Documented diagnosis of spinal muscular atrophy (SMA) Type I, II, or III; AND
Both of the following:
- The mutation or deletion of genes in chromosome 5q resulting in one of the following:
  - Homozygous gene deletion or mutation (e.g., homozygous deletion of exon 7 at locus 5q13)
  - Compound heterozygous mutation (e.g., deletion of SMN1 exon 7 [allele 1] and mutation of SMN1 [allele 2])
- Patient has at least 2 copies of SMN2; AND
Patient is not dependent on invasive ventilation or tracheostomy; AND
Patient is not dependent on the use of non-invasive ventilation beyond use for naps and nighttime sleep; AND
At least one of the following exams (based on patient age and motor ability) has been conducted to establish baseline motor ability*:
- 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); AND
One of the following:
- Patient has not previously received gene replacement therapy for the treatment of SMA (e.g., Zolgensma)
- 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)

*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.

Reauthorization Criteria:

For diagnosis of SMA:

Documentation of 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:
  - Improvement or maintenance of previous improvement of at least a two (2) point (or maximal score) increase in ability to kick
  - Improvement or maintenance of previous improvement of at least a one (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);
- One of the following HFMSE milestones:
  - Improvement or maintenance of a previous improvement of at least a three (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)
- One of the following RULM test milestones:
  - Improvement or maintenance of a previous improvement of at least a two (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)
- One of the following CHOP INTEND milestones:
  - Improvement or maintenance of a previous improvement of at least a four (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)
- One of the following MFM-32 milestones:
  - Improvement or maintenance of a previous improvement of at least a three (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)
- Improvement in the ability to sit without support for at least five (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); AND
Patient continues to not be dependent on invasive ventilation or tracheostomy; AND
Patient continues to not be dependent on the use of non-invasive ventilation beyond use for naps and nighttime sleep; 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); AND
One of the following:
- Patient has not previously received gene replacement therapy for the treatment of SMA (e.g., Zolgensma)
- 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).

Dosing:

SMA:

Less than 2 months of age: 0.15 mg/kg once daily
2 months to less than 2 years of age: 0.2 mg/kg once daily
2 years of age and older weighing less than 20 kg: 0.25 mg/kg once daily
2 years of age and older weighing 20 kg or more: 5 mg once daily

Coverage Duration:

1 year

Authorization is not covered for the following:

The use of this drug for indications not listed in this policy does not meet the coverage criteria established by the Western Health Advantage (WHA) Pharmacy and Therapeutics (P&T) Committee.

Additional Information:

Evrysdi powder must be constituted to the oral solution by a pharmacist or other healthcare provider prior to dispensing to the patient.
Evrysdi was FDA approved in August 2020 to treat SMA in adults and children two months and older. Then in May 2022 the FDA approved the label extension for infants with SMA under two months old.
Different scoring measurements of development and function may be used based on SMA phenotype: https://pediatricapta.org/includes/fact-sheets/pdfs/FactSheet_SpinalMuscularAtrophy_2021.pdf?v=1
Information about the Hammersmith Infant Neurological Examination Section 2 (HINE-2) milestones, Children’s Hospital of Philadelphia Infant Test of Neurological Disorders (CHOP-INTEND), Hammersmith Functional Motor Scale—Expanded (HFMSE), and Revised Upper Limb Module (RULM) can be found here: https://www.spinrazahcp.com/content/dam/commercial/spinraza/hcp/en_us/pdf/mobility-and-physical-ability.pdf
Information about the Motor Function Measurement with 32 items (MFM-32) can be found here: https://mfm-nmd.org/?lang=en
The Bayley Scales of Infant Development-II (BSID-II) has been updated and revised since its 1993 publication. For example, the BSID-II has been modified into to the Bayley-III. More information can be found here: http://pustaka.unp.ac.id/file/abstrak_kki/EBOOKS/Bayley%20III_Clinical_Use_and_Interpretation__Practical_Resources_for_the_Mental_Health_Professional_.pdf

Policy Review History:

06/01/2023 – New utilization management criteria approved by WHA P&T (05/16/2023).

References:

Evrysdi prescribing information. Genentech, Inc. South San Francisco, CA. September 2022.
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.
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.
Markowitz JA, Sing P, Darras BT. Spinal muscular atrophy: a clinical and research update. Pediatr Neurol. 2012;46(1):1-12.
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.
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.
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.
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.
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.
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
Evrysdi [AMCP dossier]; South San Francisco, CA: Genentech; September 2020.

Last review date: June 1, 2023