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Evrysdi (risdiplam) – Commercial and Healthcare Reform
Number: J-1000 Category: Prior Authorization
Line(s) of Business:

Commercial
Healthcare Reform
Medicare

Benefit(s):

 

Commercial:

Prior Authorization (1.):

1.    Miscellaneous Specialty Drugs Oral = Yes w/ Prior Authorization

 

Quantity Limits (1., 2., 3., or 4.)

1.    Rx Mgmt Quantity Limits = Safety/Specialty

2.    Rx Mgmt Quantity Limits = Safety/Specialty + Dose Opt

3.    Rx Mgmt Quantity Limits = Safety/Specialty + Dose Opt + Watchful

4.    Rx Mgmt Performance = MRxC = Yes

 

Healthcare Reform:  Not Applicable
Region(s):

All
Delaware
New York
Pennsylvania
West Virginia

Additional Restriction(s):

None


Drugs Products
  • Evrysdi (risdiplam)
FDA-Approved Indications:
  • Treatment of spinal muscular atrophy (SMA) in patients 2 months of age and older


Background:
  • Evrysdi is an orally administered survival motor neuron 2 (SMN2) splicing modifier designed to treat patients with SMA caused by mutations in chromosome 5q that lead to SMN protein deficiency. Evrysdi has been shown to increase exon 7 inclusion in SMN2 mRNA transcripts and production of full-length SMN protein in the brain.
  • SMA is a genetic neuromuscular disorder that leads to loss of motor function and ambulation and a reduced life expectancy.
  • SMA affects 10,000 to 25,000 children and adults in the United States.1 in 6,000 to 1 in 10,000 children are born with the disease.
  • There are 4 types of SMA, which are based on age of onset and maximum motor function achieved: very weak infants unable to sit unsupported (type 1), nonambulant patients able to sit independently (type 2), up to ambulant patients with childhood (type 3) and adult onset SMA (type 4).
  • The diagnosis of SMA is based on molecular genetic testing. The gold standard being a quantitative analysis of both SMN1 and SMN2 using multiplex ligation-dependent probe amplification (MLPA), quantitative polymerase chain reaction (qPCR) or next generation sequencing (NGS).
  • Approximately 96% of patients have homozygous absence of exons 7 and 8 of the SMN1 gene, or in some cases only of exon 7. SMN2 is intact in all SMA patients. SMA patients always carry at least 1 SMN2 copy.
  • The majority of type 1 SMA patients carry two SMN2 copies. Type 2 SMA and type 3a SMA patients carry three SMN2 copies, type 3b carry four SMN2 copies, and type 4 carry four to six SMN2 copies.
  • Symptoms of SMA include muscle weakness, delayed gross motor skills, limited mobility, breathing problems, problems eating and swallowing, and spontaneous tongue movement.
  • Common motor function measurement tests used in SMA include Motor Function Measurement (MFM), Revised Upper Limb Module (RULM), Hammersmith Infant Neurological Examination (HINE), Hammersmith Function Motor Scale Expanded (HFMSE), 6 minute walk test (6MWT), and the Children’s Hospital of Philadelphia Infant Test of Neuromuscular disorders (CHOP). The choice of assessment will reflect the aspects that are more relevant for each level of severity of the patient. Assessments should be performed routinely by a trained examiners every 6 months, unless there are special circumstances requiring different follow up.
  • In the pivotal efficacy trials for Evrysdi, all patients had types 1, 2, or 3 SMA. The primary endpoint for the trial in type 1 SMA patients was the proportion of infants sitting without support ≥ 5 seconds (as measured by Item 22 of the Bayley Scales of Infant and Toddler Development – Third Edition (BSID-III) gross motor scale). For types 2 and 3, the primary endpoint was change from baseline in motor function assessed using total score of Motor Function Measure 32 (MFM-32). All patients in both trials had at least 2 copies of SMN2. All patients had genetic confirmation of homozygous deletion or compound heterozygosity predictive loss of function of the SMN1 gene.
  • The quantity level limit of Evrysdi is 1 bottle per 24 days. If the member meets the age and weight requirements in the policy per the package insert, an authorization may be approved for 2 bottles per 24 days (PLA of 2 bottles per 20 days). A bottle of Evrysdi expires 64 days after constitution by the dispensing pharmacist.

Age and Body Weight

Recommended Daily Dosage

2 months to less than 2 years of age

0.2 mg/kg

2 years of age and older weighing < 20 kg

0.25 mg/kg

2 years of age and older weighing ≥ 20 kg

5 mg
  • Prescribing Considerations:
    • Evrsydi is primarily metabolized by flavin monooxygenase 1 and 3 (FMO1 and FMO3) and also by CYPs 1A1, 2J2, 3A4, and 3A7. Based on literature reports, pediatric patients less than 2 months of age are expected to have reduced activity of FMO3, which may result in increased exposure to Evrysdi. Safety and effectiveness in pediatric patients below the age of 2 months have not been established.
    • Avoid use in patients with hepatic impairment.
    • Based on animal studies, may cause fetal harm when administered to pregnant females. Pregnancy testing is recommended for females of reproductive potential prior to initiating Evrysdi. Effective contraception should be used during treatment and for at least 1 month after last dose.
    • Male fertility may be compromised by treatment with Evrysdi. Male patients may consider sperm preservation prior to treatment.


Approval Criteria

I.     Initial Authorization

When a benefit, coverage of Evrysdi may be approved when all of the following criteria are met (A. through H.):

A.  The member is 2 months of age or older.

B.  The member has a diagnosis of one (1) of the following (1., 2., or 3.):

1.  SMA type 1

2.  SMA type 2

3.  SMA type 3

C.  The member has at least 2 copies of the SMN 2 gene.

D.  Evrysdi is prescribed by or in consultation with a neuromuscular specialist or neurologist.

E.  The member is not using Evrysdi concomitantly with Spinraza.

F.  There is baseline documentation of the patient’s motor function test results (e.g. MFM, CHOP, HINE, RULM, HFMSE, 6MWT).

G.  The member meets one (1) of the following criteria are met (1. or 2.):

1.  The member has not previously received gene replacement therapy for the treatment of SMA.

2.  The member has received gene replacement therapy and has experienced a declination in clinical status since receipt of gene replacement therapy.

H.  The prescriber provides documentation of molecular genetic testing of 5q SMA for one (1) of the following(1., 2., or 3.):

1.  Homozygous gene deletion

2.  Homozygous conversion mutation

3.  Compound heterozygote

 

II.    Reauthorization

When a benefit, reauthorization of Evrysdi may be approved when the following criterion is met (A.):

A.    The member meets one (1) of the below criteria (1. or 2.):

1.  There is documentation demonstrating that the member is stable or shows clinically significant improvement in SMA-associated symptoms (e.g. stabilization or decreased decline in motor function compared to the predicted natural history trajectory of disease).

2.  There is documentation demonstrating stable or improved motor function test results compared to baseline (e.g. MFM, CHOP, HINE, RULM, HFMSE, 6MWT).

 

III.  Quantity Level Limit

When a benefit, additional quantities of Evrysdi may be approved when one (1) of the following criteria are met (A. or B.):

A.  The member is 2 months to 2 years of age and weighs 12.5 kg (27 lbs) or more.

B.  The member is 2 years of age or older and weighs 10 kg (22 lbs) or more.

1.  Note: If approved, enter a patient level authorization (PLA) of 2 bottles (160 mL) per 20 days at retail and mail. Additional quantities over this amount may not be approved.

 

IV.  An exception to some or all of the criteria above may be granted for select members and/or circumstances based on state and/or federal regulations. 


Limitations of Coverage

I.   Coverage of Evrysdi for disease states outside of its FDA-approved indications should be denied based on the lack of clinical data to support its effectiveness and safety in other conditions.

II.  For Commercial and HCR members with a closed formulary, a non-formulary product will only be approved if the member meets the criteria for a formulary exception in addition to the criteria outlined within this policy.


Authorization Duration
  • Commercial and HCR Plans: If approved, up to a 6 month authorization may be granted.


Automatic Approval Criteria

None


Version: J-1000-001
Effective Date Begin: 09/21/2020
Effective End Begin: 10/23/2021
Original Date: 06/01/2020
Review Date: 08/28/2020


References:

  1. Evrysdi [package insert]. South San Francisco, CA: Genentech, Inc.; August 2020.
  2. SMA Foundation. SMA Patient Resources. Available at: https://smafoundation.org/about-sma/. Accessed August 17, 2020.
  3. Mercuri E, Finkel R, Muntoni F, et al. Diagnosis and management of spinal muscular atrophy: Part 1:Recommendations for diagnosis, rehabilitation, orthopedic and nutritional care. Neuromuscular Disorders 28(2018)103-115.
  4. Finkel R, Mercuri E, Meyer O, et al. Diagnosis and management of spinal muscular atrophy: Part 2: Pulmonary and acute care; medications, supplements and immunizations; other organ systems; and ethics. Neuromuscular Disorders 28(2018)197-207.
  5. Ratni H, et al. Discovery of risdiplam, a selective survival of motor neuron‐2 (SMN2) gene splicing modifier for the treatment of spinal muscular atrophy (SMA). J. Med. Chem. 61, 6501–6517 (2018).

 

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Pharmacy policies do not constitute medical advice, nor are they intended to govern physicians' prescribing or the practice of medicine. They are intended to reflect Highmark's coverage and reimbursement guidelines. Coverage may vary for individual members, based on the terms of the benefit contract.

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