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Drug Mayzent® (siponimod) [Novartis Pharmaceuticals Corporation]

August 2019

Therapeutic area - Multiple Sclerosis

Initial approval criteria

  • Patient has a diagnosis of a relapsing form† of multiple sclerosis (MS), active secondary progressive MS (SPMS), or clinically isolated syndrome (CIS)‡ AND
  • Diagnosis is documented by a laboratory report (e.g., magnetic resonance imaging [MRI]) AND
  • Patient ≥ 18 years old AND
  • Patient CYP2C9 variant status has been tested to determine genotyping (required for dosing) AND
  • Patient has obtained a baseline electrocardiogram (ECG) AND
  • Patient has been tested for antibodies to the varicella zoster virus (VZV) or has received immunization for VZV 4 weeks prior to beginning therapy AND
  • Patient has had a baseline ophthalmic evaluation of the fundus, including the macula, before starting treatment AND
  • Patient does NOT have any of the following:
    • Recent myocardial infarction, unstable angina, stroke, transient ischemic attack, decompensated heart failure with hospitalization, or Class III/IV heart failure within the previous 6 months OR
    • Prolonged QTc interval at baseline (>500 msec) OR
    • History of Mobitz Type II second or third-degree atrioventricular block or sick sinus syndrome (unless treated with a functioning pacemaker) OR
    • CYP2C9*3/*3 genotype OR
    • Active infection, including clinically important localized infections AND
  • Siponimod will NOT be used in combination with the following:
    • Moderate or strong CYP3A4 inducers (e.g., modafinil, efavirenz, etc.) in patients with a CYP2C9*1/*3 and CYP2C9*2/*3 genotypes OR
    • Drug regimens that contain CYP2C9/CY3A4 dual inhibitors (e.g., fluconazole) or in combination with a moderate CYP2C9 inhibitor plus a moderate-to-strong CYP3A4 inhibitor OR
    • Drug regimens that contain a moderate CYP2C9/strong CYP3A4 dual inducer (e.g., rifampin or carbamazepine) or a moderate CYP2C9 inducer plus a strong CYP3A4 inducer OR
    • Other antineoplastic, immunosuppressive or immunomodulating drugs (Note: if there is a history of prior use of these drugs, consider possible unintended additive immunosuppressive effects) OR
    • Live vaccines during and at least 4 weeks after treatment AND
  • Siponimod will be prescribed by, or in consultation with, a specialist in cardiology in patients with a pre-existing cardiac condition and/or cardiovascular disease (e.g., conduction abnormalities, arrhythmias requiring treatment, heart disease, heart failure, history of cardiac arrest or myocardial infarction, cerebrovascular disease, uncontrolled hypertension, or sinoatrial heart block) AND
  • Patient will not be initiating therapy after previous treatment with alemtuzumab AND
  • Siponimod will be used as a single agent therapy AND
  • If SPMS, patient has active/progressive disease, defined as ≥ 1 of the following:
    • Patient has had ≥ 1 relapse within the previous 2 years OR
    • Patient has new and unequivocally enlarging T2 contrast-enhancing lesions as evidenced by MRI

Renewal criteria

  • Patient continues to meet above criteria AND
  • Absence of unacceptable toxicity from the drug (e.g., macular edema; severe hepatic injury; bradyarrhythmia; atrioventricular [AV] blocks; active serious infection; decreased respiratory function; progressive multifocal leukoencephalopathy [PML]; posterior reversible encephalopathy syndrome [PRES]; uncontrolled hypertension) AND
  • Patient has had an ophthalmic re-evaluation if changes in vision have been experienced AND
  • There is documented continuous monitoring of response to therapy (e.g., manifestations of MS disease activity include, but are not limited to, an increase in annualized relapse rate [ARR], development of new/worsening T2 hyperintensities or enhancing lesions on brain/spinal MRI, and progression of sustained impairment as evidenced by expanded disability status scale [EDSS], timed 25-foot walk [T25-FW)], 9-hole peg test [9-HPT])

† Diagnostic criteria for relapsing form of MS (diagnosis is based on both dissemination in time and space; unless contraindicated, MRI should be obtained even if criteria are met):

  • Dissemination in time (development/appearance of new CNS lesions over time):
    • ≥ 2 clinical attacks OR
    • 1 clinical attack AND 1 of the following:
      • MRI indicating simultaneous presence of gadolinium (Gd)-enhancing and non-enhancing lesions at any time or by a new T2- hyperintense or Gd-enhancing lesion on follow-up MRI compared to baseline scan OR
      • CSF-specific oligoclonal bands AND
  • Dissemination in space (development of lesions in distinct anatomical locations within the CNS; multifocal)
    • ≥ 2 lesions OR
    • 1 lesion AND 1 of the following:
      • Clear-cut historical evidence of a previous attack involving a lesion in a distinct anatomical location OR
      • MRI indicating ≥ 1 T2-hyperintense lesions characteristic of MS in ≥ 2 of 4 areas of the CNS (periventricular, cortical or juxtacortical, infratentorial, or spinal cord)

‡ Diagnostic criteria for CIS:

  • A monophasic clinical episode with patient-reported symptoms and objective findings reflecting a focal or multifocal inflammatory demyelinating event in the central nervous system (CNS) AND
  • Neurologic symptom duration of at least 24 hours, with or without recovery AND
  • Absence of fever or infection AND
  • Patient is not known to have multiple sclerosis

Denial criteria

  • Cytochrome p450 (CYP) 2C9 *3/*3 genotype
  • Any of the following within 6 months: myocardial infarction (MI), unstable angina (UA), stroke, transient ischemic attack (TIA), decompensated heart failure requiring hospitalization, or Class III or IV heart failure
  • Mobitz type II second-degree, third-degree atrioventricular (AV) block, or sick sinus syndrome (unless patient has a functioning pacemaker)

Quantity limits

  • CYP2C9 Genotypes: *1/*1, *1/*2, or *2/*2:
    • 2 mg/day (following titration); 30 tablets/30 days
    • Starter pack once (or for eligible treatment interruptions)
  • CYP2C9 Genotypes: *1/*3 or *2/*3:
    • 1 mg/day (following titration); 120 x 0.25 mg/30 days

Background Information

Required genotype testing is provided by Novartis’ Patient Support Program and is not covered by Medical Assistance. Questions regarding required genotype testing should be directed to Novartis’ 24-hour helpline at 877-629-9368.


MHCP Provider Call Center 651-431-2700 or 800-366-5411

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