EXTAVIA, Interferon Beta-1b BETASERON, Interferon Beta-1b Form

Interferon beta-1b (Betaseron®, Extavia®) is an amino acid glycoprotein. FDA Approved Indication(s) Betaseron and Extavia are indicated for the treatment of patients with relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria.
It is the policy of health plans affiliated with Centene Corporation® that Betaseron and Extavia are medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Multiple Sclerosis (must meet all):

1. Diagnosis of one of the following (a, b, or c): a. Clinically isolated syndrome, and one of the following (i or ii): i. Request is for Extavia; ii. If request is for Betaseron, member is contraindicated to both, or has experienced clinically significant adverse effects to one, of the following at up to maximally indicated doses: an interferon-beta agent (Avonex®, Extavia, Rebif®, or Plegridy®), glatiramer (Copaxone®, Glatopa®);Prior authorization is required for all disease modifying therapies for MS b. Relapsing-remitting MS, and one of the following (i or ii):
   i. Request is for Extavia; ii. If request is for Betaseron, failure of all of the following at up to maximally indicated doses, unless clinically significant adverse effects are experienced or all are contraindicated (1, 2, 3, and 4): 1) Dimethyl fumarate (generic Tecfidera®);
   2) Teriflunomide (generic Aubagio®);
   3) Fingolimod (Gilenya®); 4) An interferon-beta agent (Avonex, Extavia, Rebif, or Plegridy) or glatiramer (Copaxone, Glatopa); Prior authorization may be required for all disease modifying therapies for MS c. Secondary progressive MS and one of the following (i or ii): i. Request is for Extavia; Page 1 of 8

   CLINICAL POLICY Interferon Beta-1b ii. If request is for Betaseron, failure of an interferon-beta agent (Avonex, Extavia, Rebif, or Plegridy) at up to maximally indicated doses, unless clinically significant adverse effects are experienced or all are contraindicated;

2. Age ≥ 12 years;
   3. Interferon beta-1b is not prescribed concurrently with other disease modifying therapies for MS (see Appendix D);
3. Documentation of both baseline number of relapses per year and expanded disability status scale (EDSS) score;
4. Dose does not exceed 0.25 mg (1 vial) every other day. Approval duration: 6 months B. Other diagnoses/indications (must meet 1 or 2):
5. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.PMN.16 for Medicaid; or
6. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.PMN.53 for Medicaid.
   II. Continued Therapy A. Multiple Sclerosis (must meet all):

7. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; b. Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B);

   2. Member meets one of the following (a or b): a. If member has received < 1 year of total treatment: Member is responding positively to therapy; b. If member has received ≥ 1 year of total treatment: Member meets one of the following (i, ii, iii, or iv): i. Member has not had an increase in the number of relapses per year compared to baseline; ii. Member has not had ≥ 2 new MRI-detected lesions; iii. Member has not had an increase in EDSS score from baseline; iv. Medical justification supports that member is responding positively to therapy; Page 2 of 8

   CLINICAL POLICY Interferon Beta-1b

8. Interferon beta-1b is not prescribed concurrently with other disease modifying therapies for MS (see Appendix D);
9. If request is for a dose increase, new dose does not exceed 0.25 mg (1 vial) every other day. Approval duration:
   If member has received < 1 year of total treatment – up to a total of 12 months of treatment If member has received ≥ 1 year of total treatment – 12 months B. Other diagnoses/indications (must meet 1 or 2):
10. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.PMN.16 for Medicaid; or

11. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.PMN.53 for Medicaid.
    III. Diagnoses/Indications for which coverage is NOT authorized:
    A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off label use policy – CP.PMN.53 for Medicaid or evidence of coverage documents; B. Primary progressive MS. IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key EDSS: expanded disability status scale
    FDA: Food and Drug Administration MS: multiple sclerosis Appendix B: Therapeutic Alternatives
    This table provides a listing of preferred alternative therapy recommended in the approval criteria. The drugs listed here may not be a formulary agent for all relevant lines of business and may require prior authorization.
    Drug Name Dosing Regimen Dose Limit/ Maximum Dose 14 mg/day Avonex: 30 mcg/week Rebif: 44 mcg TIW teriflunomide (Aubagio®) Avonex®, Rebif® (interferon beta-1a) 7 mg or 14 mg PO QD Avonex: 30 mcg IM Q week Rebif: 22 mcg or 44 mcg SC TIW Page 3 of 8

    CLINICAL POLICY Interferon Beta-1b Drug Name Dosing Regimen Dose Limit/ Maximum Dose 125 mcg/2 weeks 125 mcg SC Q2 weeks 20 mg SC QD or 40 mg SC TIW Plegridy® (peginterferon beta-1a) glatiramer acetate (Copaxone®, Glatopa®) fingolimod (Gilenya®) 0.5 mg PO QD 120 mg PO BID for 7 days, dimethyl fumarate (Tecfidera®) followed by 240 mg PO BID Therapeutic alternatives are listed as Brand name® (generic) when the drug is available by brand name only and generic (Brand name®) when the drug is available by both brand and generic. 20 mg/day or 40 mg TIW 0.5 mg/day 480 mg/day Appendix C: Contraindications/Boxed Warnings • Contraindication(s): history of hypersensitivity to natural or recombinant interferon beta, albumin or mannitol • Boxed warning(s): none reported Appendix D: General Information • Disease-modifying therapies for MS are: glatiramer acetate (Copaxone®, Glatopa®), interferon beta-1a (Avonex®, Rebif®), interferon beta-1b (Betaseron®, Extavia®), peginterferon beta-1a (Plegridy®), dimethyl fumarate (Tecfidera®), diroximel fumarate (Vumerity®), monomethyl fumarate (Bafiertam™), fingolimod (Gilenya®, Tascenso ODT™), teriflunomide (Aubagio®), alemtuzumab (Lemtrada®), mitoxantrone (Novantrone®), natalizumab (Tysabri®), ocrelizumab (Ocrevus®), cladribine (Mavenclad®), siponimod (Mayzent®), ozanimod (Zeposia®), ponesimod (Ponvory™), ublituximab-xiiy (Briumvi™), and ofatumumab (Kesimpta®) • Of the disease-modifying therapies for MS that are FDA-labeled for CIS, only the interferon products, glatiramer, and teriflunomide have demonstrated any efficacy in decreasing the risk of conversion to MS compared to placebo. This is supported by the American Academy of Neurology 2018 MS guidelines. V. Dosage and Administration
    Drug Name Interferon beta-1b (Betaseron) Interferon beta-1b (Extavia) Dosing Regimen Generally start at 0.0625 mg SC every other day, and increase over a six-week period to 0.25 mg SC every other day
    Generally start at 0.0625 mg SC every other day, and increase over a six-week period to 0.25 mg SC every other day Maximum Dose 0.25 mg QOD 0.25 mg QOD VI. Product Availability
    Drug Name Interferon beta-1b (Betaseron) Interferon beta-1b (Extavia) Availability Single-use vial: 0.3 mg Single-use vial: 0.3 mg Page 4 of 8

    CLINICAL POLICY Interferon Beta-1b VII.