Multiple Sclerosis (MS) Therapies - NC Standard

Restricted Product(s):

Restriction applies to brand and generic products

• Aubagio® (teriflunomide)
• Avonex® (interferon Beta-1a)
• Bafiertam™(monomethyl fumarate)
• Betaseron® (interferon Beta-1b)
• Copaxone® (glatiramer acetate)
• Dimethyl fumarate (Tecfidera®)
• Extavia® (interferon Beta-1b)
• Glatiramer acetate (Copaxone®)
• Glatopa® (glatiramer acetate)
• Gilenya® (fingolimod)
• Kesimpta® (ofatumumab)
• Mayzent® (siponimod)
• Mavenclad® (cladridine)
• Plegridy® (peginterferon Beta-1a)
• Ponvory® (ponesimod)
• Rebif® (interferon Beta-1a)
• Tecfidera® (dimethyl fumarate)
• Tascenso ODT™(fingolimod)
• Vumerity® (diroximel fumarate)

FDA Approved Use:

• For the treatment of relapsing forms of multiple sclerosis to reduce the frequency of clinical exacerbations. Patients with multiple sclerosis in whom efficacy has been demonstrated include patients who have experienced a first clinical episode and have MRI features consistent with multiple sclerosis. Patients with clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease.

Criteria for Approval of Restricted Product(s):

Initial Coverage Criteria

1. The patient’s age is appropriate based on intended use and FDA labeling for requested agent; AND
2. The patient has a diagnosis of Relapsing-remitting, Secondary-progressive, or Progressive-relapsing MS; OR
   1. The patient will be using for treatment at time of first demyelinating event to delay development or progression to multiple sclerosis; AND
3. The patient must still either be able to walk at least a few steps with or without aid, or alternatively must have some functional arm/ hand use consistent with performing activities of daily living; AND
4. The patient is NOT receiving concurrent therapy with two or more disease-modifying drugs for multiple sclerosis, including glatiramer (Copaxone, Glatopa), interferon beta-1b (Betaseron, Extavia), interferon beta-1a (Avonex, Rebif), peginterferon beta-1a (Plegridy), fingolimod (Gilenya, Tascenso ODT), teriflunomide (Aubagio), dimethyl fumarate (Tecfidera), monomethyl fumarate (Bafiertam), ofatumumab (Kesimpta), alemtuzumab (Lemtrada), siponimod (Mayzent), cladridine (Mavenclad), ocrelizumab (Ocrevus), ponesimod (Ponvory), natalizumab (Tysabri, Tyruko), diroximel fumarate (Vumerity), ozanimod (Zeposia) and ublituximab-xiiy (Briumvi); AND
5. The request is for dimethyl fumarate (generic Tecfidera) or glatiramer acetate (generic Copaxone or Glatopa) or fingolimod (generic Gilenya) or teriflunomide (generic Aubagio); OR
6. The request is for Avonex, Betaseron, Kesimpta, Mavenclad, Mayzent, Plegridy or Rebif; AND
   1. The patient has tried and had an inadequate response, intolerance, or hypersensitivity to ONE of the following: dimethyl fumarate (generic Tecfidera), glatiramer acetate (generic Copaxone or Glatopa), fingolimod (generic Gilenya), teriflunomide (generic Aubagio) (medical record documentation required); OR
      1. The patient has an FDA labeled contraindication to ALL of the following: dimethyl fumarate (generic Tecfidera), glatiramer acetate (generic Copaxone or Glatopa), fingolimod (generic Gilenya), teriflunomide (generic Aubagio) (medical record documentation required); OR
   2. The patient has highly active MS disease activity (medical record documentation required); AND
      1. The patient has ≥ 2 relapses in the previous year; AND
         1. The patient has ≥ 1 gadolinium enhancing lesion on MRI; OR
         2. The patient has significant increase in T2 lesion load compared with previous MRI; OR
   3. The patient has been treated with at least 3 MS agents from different drug classes (medical record documentation required); OR
7. The request is for Gilenya; AND
   1. ONE of the following:
      1. The patient has tried and had an inadequate response, intolerance, or hypersensitivity to ONE of the following: Avonex, Betaseron, Kesimpta, Mavenclad, Mayzent, Plegridy, Rebif, Zeposia; OR
         1. The patient has an FDA labeled contraindication to ALL of the following: Avonex, Betaseron, Kesimpta, Mavenclad, Mayzent, Plegridy, Rebif, Zeposia; OR
      2. The patient has highly active MS disease activity (medical record documentation required); AND
         1. The patient has ≥ 2 relapses in the previous year; AND
            1. The patient has ≥ 1 gadolinium enhancing lesion of MRI; OR
            2. The patient has significant increase in T2 lesion load compared with previous MRI; OR
      3. The patient has been treated with at least 3 MS agents from different drug classes (medical record documentation required); AND
   2. For patients requesting the use of Gilenya, the patient will have received an electrocardiogram prior to initiating treatment (baseline assessment or at time of first dose); AND
   3. The patient had a documented serious adverse event that required medical intervention to generic fingolimod that is not anticipated with Brand Gilyena (medical record documentation required); AND
   4. If the request is for Gilenya 0.25mg, the patient is > 10 years of age AND weighs < 40 kg; OR
8. The request is for Aubagio; AND
   1. ONE of the following:
      1. The patient has tried and had an inadequate response, intolerance, or hypersensitivity to ONE of the following: Avonex, Betaseron, Kesimpta, Mavenclad, Mayzent, Plegridy, Rebif, Zeposia; OR
         1. The patient has an FDA labeled contraindication to ALL of the following: Avonex, Betaseron, Kesimpta, Mavenclad, Mayzent, Plegridy, Rebif, Zeposia; OR
      2. The patient has highly active MS disease activity (medical record documentation required); AND
         1. The patient has ≥ 2 relapses in the previous year; AND
            1. The patient has ≥ 1 gadolinium enhancing lesion of MRI; OR
            2. The patient has significant increase in T2 lesion load compared with previous MRI; OR
      3. The patient has been treated with at least 3 MS agents from different drug classes (medical record documentation required); AND
   2. For patients requesting the use of Aubagio, the patient had a documented serious adverse event that required medical intervention to generic teriflunomide that is not anticipated with Brand Aubagio (medical record documentation required); OR
9. The request is for Bafiertam, Ponvory, or Vumerity; AND
   1. BOTH of the following:
      1. The patient has tried and had an inadequate response, intolerance, or hypersensitivity to ONE of the following: Avonex, Betaseron, Kesimpta, Mavenclad, Mayzent, Plegridy, Rebif, Zeposia; OR
         1. The patient has an FDA labeled contraindication to ALL of the following: Avonex, Betaseron, Kesimpta, Mavenclad, Mayzent, Plegridy, Rebif, Zeposia; AND
      2. The patient has tried and had an inadequate response, intolerance, or hypersensitivity to TWO of the following: dimethyl fumarate (generic Tecfidera), glatiramer acetate (generic Copaxone or Glatopa), fingolimod (generic Gilenya), teriflunomide (generic Aubagio) (medical record documentation required); OR
         1. The patient has an FDA labeled contraindication to ALL of the following: dimethyl fumarate (generic Tecfidera), glatiramer acetate (generic Copaxone or Glatopa), fingolimod (generic Gilenya), teriflunomide (generic Aubagio) (medical record documentation required); OR
   2. The patient has highly active MS disease activity (medical record documentation required); AND
      1. The patient has ≥ 2 relapses in the previous year; AND
         1. The patient has ≥ 1 gadolinium enhancing lesion of MRI; OR
         2. The patient has significant increase in T2 lesion load compared with previous MRI; AND
      2. The patient has tried and had an inadequate response, intolerance, or hypersensitivity to dimethyl fumarate (generic Tecfidera) (medical record documentation required); OR
   3. The patient has been treated with at least 3 MS agents from different drug classes (medical record documentation required); AND
      1. The patient has tried and had an inadequate response, intolerance, or hypersensitivity to dimethyl fumarate (generic Tecfidera) (medical record documentation required); OR
10. The request is for Extavia; AND
    1. BOTH of the following:
       1. The patient has tried and had an inadequate response, intolerance, hypersensitivity to, or has an FDA labeled contraindication to the preferred beta 1b product, Betaseron; AND
       2. The patient has tried and had an inadequate response, intolerance, or hypersensitivity to TWO of the following: dimethyl fumarate (generic Tecfidera), glatiramer acetate (generic Copaxone or Glatopa), fingolimod (generic Gilenya), teriflunomide (generic Aubagio) (medical record documentation required); OR
          1. The patient has an FDA labeled contraindication to ALL of the following: dimethyl fumarate (generic Tecfidera), glatiramer acetate (generic Copaxone or Glatopa), fingolimod (generic Gilenya), teriflunomide (generic Aubagio) (medical record documentation required); OR
    2. The patient has highly active MS disease activity (medical record documentation required); AND
       1. The patient has ≥ 2 relapses in the previous year; AND
          1. The patient has ≥ 1 gadolinium enhancing lesion of MRI; OR
          2. The patient has significant increase in T2 lesion load compared with previous MRI; OR
    3. The patient has been treated with at least 3 MS agents from different drug classes (medical record documentation required); OR
11. The request is for Tascenso ODT; AND
    1. BOTH of the following:
       1. The patient has tried and had an inadequate response, intolerance, or hypersensitivity to ONE of the following: Avonex, Betaseron, Kesimpta, Mavenclad, Mayzent, Plegridy, Rebif, Zeposia; OR
          1. The patient has an FDA labeled contraindication to ALL of the following: Avonex, Betaseron, Kesimpta, Mavenclad, Mayzent, Plegridy, Rebif, Zeposia; AND
       2. The patient has tried and had an inadequate response, intolerance, or hypersensitivity to ONE of the following: dimethyl fumarate (generic Tecfidera), glatiramer acetate (generic Copaxone or Glatopa), fingolimod (generic Gilenya), teriflunomide (generic Aubagio) (medical record documentation required); OR
          1. The patient has an FDA labeled contraindication to ALL of the following: dimethyl fumarate (generic Tecfidera), glatiramer acetate (generic Copaxone or Glatopa), fingolimod (generic Gilenya), teriflunomide (generic Aubagio) (medical record documentation required); OR
    2. The patient has highly active MS disease activity (medical record documentation required); AND
       1. The patient has ≥ 2 relapses in the previous year; AND
          1. The patient has ≥ 1 gadolinium enhancing lesion of MRI; OR
          2. The patient has significant increase in T2 lesion load compared with previous MRI; OR
    3. The patient has been treated with at least 3 MS agents from different drug classes (medical record documentation required); AND
    4. The patient had a documented serious adverse event that required medical intervention to generic fingolimod that is not anticipated with Brand Tascenso ODT (medical record documentation required); AND
    5. The patient will have received an electrocardiogram prior to initiating treatment (baseline assessment or at time of first dose); OR
12. The request is for Copaxone; AND
    1. ONE of the following:
       1. The patient has tried and had an inadequate response, intolerance, or hypersensitivity to ONE of the following: Avonex, Betaseron, Kesimpta, Mavenclad, Mayzent, Plegridy, Rebif, Zeposia; OR
          1. The patient has an FDA labeled contraindication to ALL of the following: Avonex, Betaseron, Kesimpta, Mavenclad, Mayzent, Plegridy, Rebif, Zeposia; OR
       2. The patient has highly active MS disease activity (medical record documentation required); AND
          1. The patient has ≥ 2 relapses in the previous year; AND
             1. The patient has ≥ 1 gadolinium enhancing lesion of MRI; OR
             2. The patient has significant increase in T2 lesion load compared with previous MRI; OR
       3. The patient has been treated with at least 3 MS agents from different drug classes (medical record documentation required); AND
    2. The patient had a documented serious adverse event that required medical intervention to generic glatiramer acetate that is not anticipated with Brand Copaxone (medical record documentation required); OR
13. The request is for Brand Tecfidera; AND
    1. ONE of the following:
       1. The patient has tried and had an inadequate response, intolerance, or hypersensitivity to ONE of the following: Avonex, Betaseron, Mavenclad, Mayzent, Plegridy, Rebif, Zeposia; OR
          1. The patient has an FDA labeled contraindication to ALL of the following: Avonex, Betaseron, Kesimpta, Mavenclad, Mayzent, Plegridy, Rebif, Zeposia; OR
       2. The patient has highly active MS disease activity (medical record documentation required); AND
          1. The patient has ≥ 2 relapses in the previous year; AND
             1. The patient has ≥ 1 gadolinium enhancing lesion of MRI; OR
             2. The patient has significant increase in T2 lesion load compared with previous MRI; OR
       3. The patient has been treated with at least 3 MS agents from different drug classes (medical record documentation required); AND
    2. The patient had a documented serious adverse event that required medical intervention to generic dimethyl fumarate that is not anticipated with Brand Tecfidera (medical record documentation required); AND
14. The patient is being managed by or in consultation with a specialist in the area of the patient’s diagnosis (e.g., neurologist); AND
15. The prescribed dose and quantity are appropriate based on intended use and FDA labeling; AND
16. For formularies that exclude (non-formulary) the requested medication, Non-formulary Exception Criteria applies.

Duration of Approval: 365 days (1 year)

Continuation Coverage Criteria

1. The patient has been previously approved with Blue Cross and Blue Shield of North Carolina (Blue Cross NC) or would have met initial criteria for approval upon the start of therapy; AND
   1. Patients requesting the use of a brand medication with an available generic, the patient had a documented serious adverse event that required medical intervention to the generic medication that is not anticipated with the brand (medical record documentation required); AND
2. The patient has experienced clinical benefit from treatment with the requested agent (medical record documentation required); AND
3. The patient is NOT receiving concurrent therapy with two or more disease-modifying drugs for multiple sclerosis, including glatiramer (Copaxone, Glatopa), interferon beta-1b (Betaseron, Extavia), interferon beta-1a (Avonex, Rebif), peginterferon beta-1a (Plegridy), fingolimod (Gilenya, Tascenso ODT), teriflunomide (Aubagio), dimethyl fumarate (Tecfidera), monomethyl fumarate (Bafiertam), ofatumumab (Kesimpta), alemtuzumab (Lemtrada), siponimod (Mayzent), cladridine (Mavenclad), ocrelizumab (Ocrevus), ponesimod (Ponvory), natalizumab (Tysabri, Tyruko), diroximel fumarate (Vumerity), ozanimod (Zeposia) and ublituximab-xiiy (Briumvi); AND
4. The prescribed dose and quantity are appropriate based on intended use and FDA labeling; AND
5. The patient continues to be managed by or in consultation with a specialist in the area of the patient’s diagnosis (e.g., neurologist); AND
6. For formularies that exclude (non-formulary) the requested medication, Non-formulary Exception Criteria applies.

Duration of Approval: 365 days (1 year)

Quantity limitations apply to brand and associated generic products

Quantity Limit Exception Criteria:

1. The quantity (dose) requested is for documented titration purposes at the initiation of therapy (authorization for a 90 day titration period); AND
2. The prescribed dose cannot be achieved using a lesser quantity of a higher strength; AND
3. The quantity (dose) requested does not exceed the maximum FDA labeled dose, when specified, or to the safest studied dose per the manufacturer’s product insert; OR
4. If the quantity (dose) requested exceeds the maximum FDA labeled dose, when specified, or to the safest studied dose per the manufacturer’s product insert, then the prescriber must submit documentation in support of therapy with a higher dose for the intended diagnosis (submitted documentation may include medical records OR fax form which reflects medical record documentation that shows the length of time the requested dose has been used, and what other medications and doses have been tried and failed).

Duration of Approval: 365 days (1 year)

All information referenced is from FDA package insert unless otherwise noted below.

Policy Implementation/Update Information:

Criteria and treatment protocols are reviewed annually by the Blue Cross NC P&T Committee, regardless of change. This policy is reviewed in Q4 annually.

December 2023: Criteria update: Addition of new to market biosimilar (Tyruko) to the list of medications stating the patient is not receiving therapy with two or more disease-modifying drugs for multiple sclerosis and added to the MS product reference table.

July v2 2023: Criteria update: Added requirement to continuation criteria (to align with initial criteria) for patients requesting the use of a brand medication with an available generic, the patient had a documented serious adverse event that required medical intervention to the generic medication that is not anticipated with the brand.

July 2023: Criteria change: Added age requirement for criteria. Added the patient is being managed by or in consultation with a specialist in the area of the patient’s diagnosis. Added teriflunomide (generic Aubagio) and glatiramer acetate (Glatopa) to preferred products. Moved brand Gilenya and brand Aubagio to non-preferred products. Added the prescribed dose and quantity are appropriate based on intended use and FDA labeling. Added continuation criteria.

April 2023: Criteria update: Added Gilenya 0.25mg capsules to policy for use in patients > 10 years of age and weight < 40kg. Added Gilenya 0.25mg capsules to quantity limits.

March 2023: Criteria update: Addition of Teriflunomide (generic Aubagio) to the policy requiring use of generic prior to requesting brand Aubagio. Addition of new to market ublituximab-xiiy (Briumvi) to the list of medications stating the patient is not receiving therapy with two or more disease-modifying drugs for multiple sclerosis.

January 2023: Criteria update: Addition of new strength of Tascenso ODT 0.5 mg to the policy. Addition of fingolimod (generic Gilenya) to the policy.

November 2022: Criteria update: Clarified restriction applies to all brand and generic products

August 2022: Criteria change: Addition of new to market Tascenso ODT to the policy

July 2022: Criteria change (Bafiertam, Ponvory, or Vumerity): Updated if request for Bafiertam, Ponvory, or Vumerity, require tried and inadequate response, intolerance, or hypersensitivity to BOTH dimethyl fumarate (generic Tecfidera) AND glatiramer acetate (generic Copaxone).

March 2022: Criteria update: Addition of new to market Mayzent starter pack and Mayzent 1 mg tablets.

June 2021: Criteria update: Moved Zeposia to its own policy.

April 2021: Criteria update: Addition of new to market Ponvory to policy

April 2021: Criteria change: Nonpreferred products require trial and failure of one preferred brand and one preferred generic product. Preferred brand products require a trial and failure of one generic product. Copaxone requires a trial and failure of glatiramer. Kesimpta now a preferred Brand product.

September 2020: Criteria change: Added Kesimpta to policy. Brand Tecfidera or Vumerity requests require a trial and failure or contraindication/intolerance to dimethyl fumarate (generic Tecfidera).

September 2020: Criteria update: Added generic dimethyl fumarate to the policy.

August 2020: Criteria update: Added new to market Bafiertam to policy.

June 2020: Criteria update: Added Zeposia to the policy.

April 2020: Criteria update: Clarified duration of approval is 1095 days (3 years). Updated QL on Mavenclad Pak.

Feb 2020: Criteria update: Removed Zinbryta from policy (product discontinued).

Jan 2020: Criteria update: removed pre-requisites for Mavenclad

Nov 2019: Criteria update: Added new to market Vumerity to policy

Oct 2019: Criteria update: removed pre-requisites for Mayzent

May 2019: Criteria Update: added coverage new to market Mavenclad and Mayzent to policy

January 2019: added coverage requirement for Glatopa and quantity limits

Oct 2017: added new to market generic Copaxone to policy

Jul 2017: reformatted criteria; clarified Gilenya electrocardiogram to indicate an assessment prior to therapy.

Jun 2017: fixed error from “Zinbryta (teriflunomide)” to the correct “Zinbryta (daclizumab)”

Jan 2017: reviewed for ASO Net Results

Jul 2016: revised policy; added quantity limits to all medications listed in this policy; Removed question regarding FDA contraindications from all medications. Added Zinbryta to coverage criteria.

Jan 2011: original utilization management criteria issued.