Coverage of any drug intervention discussed in the plans prior authorization guideline is subject to the limitations and exclusions outlined in the member's benefit certificate or policy and to applicable state and/or federal laws. TYSABRI (natalizumab) MB9854

Covered Service: Yes Prior Authorization Yes Required: Must be prescribed by a neurology specialist or a Additional gastroenterology specialist with prior authorization through Information: Navitus. Medicare Policy: Prior authorization is dependent on the member’s Medicare coverage. Prior authorization is not required for Medicare Cost products (Dean Care Gold) and Medicare Supplement (Select) when this drug is provided by participating providers. Prior authorization is required if a member has Medicare primary and the plan secondary coverage. This policy is not applicable to our Medicare Replacement products. BadgerCare Plus Prescription drug benefits are administered by the Wisconsin Policy: Medicaid program. Office administered pharmacy benefits are covered by the plan when covered under the Wisconsin Medicaid fee-for-service program and not paid on a fee-for- service basis by the State of Wisconsin Medicaid program.

Plan Approved Criteria: 1.0 Injections of drugs that are administered at an excessive frequency or dose are not medically necessary. Frequency or dosing are considered excessive when services are performed more frequently or at a higher dose than listed in the FDA-approved package insert, listed in this document or generally accepted by peers and the reason for additional services is not justified by submitted documentation of clinical evidence. Route of administration of injectable drugs should follow the FDA-approved package insert.

Initial Criteria: 1.0 A clinical diagnosis of relapsing multiple sclerosis (MS) (including active secondary progressive disease, relapsing-remitting disease, and clinically isolated syndrome) and all of the following: 1.1 Member has a contraindication, allergy, intolerance, or failure of an adequate trial of an interferon-based product (e.g. AVONEX, PLEGRIDY, REBIF, EXTAVIA) or a glatiramer product (e.g. COPAXONE); AND 1.2 Member has a contraindication, allergy, intolerance, or failure of an adequate trial of TECFIDERA, GILENYA, or AUBAGIO; AND

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Coverage of any drug intervention discussed in the plans prior authorization guideline is subject to the limitations and exclusions outlined in the member's benefit certificate or policy and to applicable state and/or federal laws. 1.3 Steps 1.1 and 1.2 may be waived for members with high risk/aggressive disease (see Comments section for definition) 1.4 Member has had anti-JCV antibody testing with ELISA prior to initiating treatment and annually thereafter. 1.5 Maximum of 6 infusions in a 6 month period 2.0 A clinical diagnosis of moderate-to-severe Crohn’s disease (CD) and all of the following: 2.0 Member has had an inadequate response to, or are unable to tolerate at least one medication in each of these categories: 2.0.1 Anti-inflammatory drugs (e.g. sulfasalazine) 2.0.2 Corticosteroids 2.0.3 Formulary self-injectable TNF-α inhibitors (e.g. HUMIRA) 2.0.4 Formulary medical benefit infusables (ENTYVIO, an infliximab product) 2.1 Member has had anti-JCV antibody testing with ELISA prior to initiating treatment and annually thereafter. 2.2 Maximum of 3 infusions in a 3 month period 2.2.1 Note – CD members that have not experienced therapeutic benefit after 12 weeks of induction therapy should be discontinued and may not be covered

Continuation Criteria: 1.1 MS: After initial 6 months of therapy, a maximum of 12 infusions in a 1 year period may be considered medically necessary when documentation indicate that member is not receiving natalizumab in combination with any therapy noted in section 5.1 and is continued to be regularly seen by a provider specializing in care of MS members. 1.2 CD: After 3 months of therapy, a maximum of 12 infusions in a 1 year period may be considered medically necessary when documentation (including chart notes) indicate that there is disease stability or improvement. Examples of stability or improvement include laboratory assessment (e.g. CRP, hemoglobin, ESR, WBC, albumin), or symptom assessment (e.g. bleeding, stooling pattern, abdominal pain, extraintestinal complaints, fatigue), or endoscopy results.

Comment(s): 2.0 Criteria for high risk/aggressive MS includes one of the following (with chart documentation): 2.1 Multiple spinal cord lesions (≥2)

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Coverage of any drug intervention discussed in the plans prior authorization guideline is subject to the limitations and exclusions outlined in the member's benefit certificate or policy and to applicable state and/or federal laws. 2.2 Brainstem/infratentorial lesions (≥1) 2.3 Significant disease burden on MRI (≥10 lesions) 2.4 Short interval between relapses (≥2 relapses in ≤2 years) 2.5 Treatment failure (clinically or radiographically) with a previous disease- modifying treatment 2.6 Incomplete recovery from previous relapse (e.g. residual symptoms remaining) 2.7 Motor-based relapse (e.g. gait disturbances) 3.0 For all indications, quantity limit is 300 mg for each infusion. 4.0 In use for MS, 4.1 Concurrent use with other disease modifying treatments (e.g. interferons, COPAXONE, GLATOPA, GILENYA, AUBAGIO, or TECFIDERA), B cell targeted therapy (e.g. rituximab, belimumab, ofatumumab), or lymphocyte trafficking blockers (e.g. alemtuzumab, mitoxantrone) is considered experimental and investigational by the plan because there is a lack of reliable evidence that use of ocrelizumab in combination with other treatments is more effective than use of ocrelizumab alone. 4.2 For purpose of this policy, ‘failure’ is defined as: 4.2.1 Member has increasing relapses (defined as two or more relapses in a year, or one severe relapse associated with either poor recovery or MRI lesion progression); OR 4.2.2 Member has lesion progression verified by MRI (increased number or volume of lesions, T2 hyperintense lesions, or T1 hypointense lesions); OR 4.2.3 Member has worsening disability (sustained worsening of neurological examination findings). 5.0 *Coding specifications *Codes and descriptors listed in this document are provided for informational purposes only and may not be all inclusive or current. Listing of a code in this drug policy does not imply that the service described by the code is a covered or non-covered service. Benefit coverage for any service is determined by the member’s policy of health coverage with the plan. Inclusion of a code in the table does not imply any right to reimbursement or guarantee claim payment. Other drug or medical policies may also apply.

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Coverage of any drug intervention discussed in the plans prior authorization guideline is subject to the limitations and exclusions outlined in the member's benefit certificate or policy and to applicable state and/or federal laws. 5.1 NDC and HCPCS codes Medication Name How Supplied National Drug Brand Generic Code (NDC) HCPCS code TYSABRI natalizumab 20 mg/mL single use 64406-0008-01 J2323 vial

6.0 NOTE: The use of physician samples or manufacturer discounts does not guarantee later coverage under the provisions of the medical certificate and/or pharmacy benefit. All criteria must be met in order to obtain coverage of the listed drug product.

Committee/Source Date(s) Document Utilization Management Committee/ Medical Affairs/ Created: Navitus P&T Committee December 13, 2006 Revised: Medical Director Committee/Medical Affairs/Pharmacy Practice Leader May 16, 2012 Medical Director Committee/Medical Affairs/ Pharmacist November 18, 2015 Medical Policy Committee/Quality and Care Management/Pharmacy Services August 17, 2016 Medical Policy Committee/Quality and Care Management Division/Pharmacy Services April 19, 2017 Medical Policy Committee/Quality and Care Management Division/Pharmacy Services September 20, 2017 Medical Policy Committee/Quality and Care Management Division/Pharmacy Services November 15, 2017 Medical Policy Committee/Quality and Care Management Division/Pharmacy Services April 18, 2018 Medical Policy Committee/Health Services Division/Pharmacy Services August 15, 2018 Medical Policy Committee/Health Services Division/Pharmacy Services January 16, 2019 Medical Policy Committee/Health Services Division/Pharmacy Services April 15, 2020 Medical Policy Committee/Health Services Division/Pharmacy Services April 21, 2021 Reviewed: Utilization Management Committee/ Medical Affairs December 10, 2008 Utilization Management Committee/Medical Affairs/Pharmacy Practice Leader December 28, 2011 Medical Director Committee/Medical Affairs/Pharmacy Practice Leader May 16, 2012

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Coverage of any drug intervention discussed in the plans prior authorization guideline is subject to the limitations and exclusions outlined in the member's benefit certificate or policy and to applicable state and/or federal laws. Committee/Source Date(s) Medical Director Committee/Medical Affairs/ Pharmacist December 18, 2013 Medical Director Committee/Medical Affairs/ Pharmacist November 19, 2014 Medical Director Committee/Medical Affairs/ Pharmacist November 18,2015 Medical Policy Committee/Quality and Care Management/Pharmacy Services August 17, 2016 Medical Policy Committee/Quality and Care Management Division/Pharmacy Services April 17, 2017 Medical Policy Committee/Quality and Care Management Division/Pharmacy Services September 20, 2017 Medical Policy Committee/Quality and Care Management Division/Pharmacy Services November 15, 2017 Reviewed: Medical Policy Committee/Quality and Care Management Division/Pharmacy Services April 18, 2018 Medical Policy Committee/Health Services Division/Pharmacy Services August 15, 2018 Medical Policy Committee/Health Services Division/Pharmacy Services January 16, 2019 Medical Policy Committee/Health Services Division/Pharmacy Services April 17, 2019 Medical Policy Committee/Health Services Division/Pharmacy Services April 15, 2020 Medical Policy Committee/Health Services Division/Pharmacy Services April 21, 2021 Deleted: Medical Director Committee/Medical Affairs/ Pharmacist October 15, 2014 Reinstated: Medical Director Committee/Medical Affairs/ Pharmacist November 19, 2014

Effective: 05/01/2021 Published: 05/01/2021

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