Multiple Sclerosis – Unified Formulary

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Pharmacy Policy Multiple Sclerosis – Unified Formulary

Policy Number: 9.219 Version Number: 1.3 Version Effective Date: 7/1/2021

Product Applicability All Plan+ Products

Well Sense Health Plan Boston Medical Center HealthNet Plan New Hampshire Medicaid MassHealth ACO MassHealth MCO Qualified Health Plans/ConnectorCare/Employer Choice Direct

Senior Care Options

Note: Disclaimer and audit information is located at the end of this document.

Prior Authorization Policy

Reference Table: Drugs that require PA No PA ® ® Aubagio (teriflunomide) Copaxone (glatiramer)§ Bafiertam ® (monomethyl fumarate) ® Gilenya (fingolimod)§ Mayzent® (siponimod) ® Tecfidera (dimethyl fumarate)§ PD * Vumerity® (diroximel fumarate) Zeposia® (ozanimod) § Brand Preferred over generic equivalents. In general, MassHealth requires a trial of the preferred drug or clinical rationale for prescribing the non-preferred drug generic equivalent. PD Preferred Drug. In general, MassHealth requires a trial of the preferred drug or clinical rationale for prescribing a non- preferred drug within a therapeutic class. Please note, for Tecfidera® (dimethyl fumarate) a trial with a preferred agent is not required prior to approval of a non-preferred agent. *A-rated generic available. Both brand and A-rated generic require PA.

+ Plan refers to Boston Medical Center Health Plan, Inc. and its affiliates and subsidiaries offering health coverage plans to enrolled members. The Plan operates in Massachusetts under the trade name Boston Medical Center HealthNet Plan and in other states under the trade name Well Sense Health Plan. Multiple Sclerosis - PUF

Procedure: Approval Diagnosis: Clinically Isolated Syndrome (CIS): Aubagio®, Bafiertam®, Gilenya®, Mayzent®, dimethyl fumarate, Vumerity®, Zeposia® Relapse-remitting MS (RRMS) and Active Secondary-progressive MS (SPMS)*: Aubagio®, Bafiertam®, Gilenya®, Mayzent®, dimethyl fumarate, Vumerity®, Zeposia®

Note:  *For requests that document SPMS, active disease must be confirmed. Please refer to the appendix for additional information. If there is no documentation to confirm active SPMS, please forward to clinical review for case-by-case evaluation and prescriber outreach. Approval Criteria: Prescriber provides documentation of ALL of the following: 1. Appropriate diagnosis* Aubagio® 2. Provider is a neurologist or consult notes from a neurology office are (teriflunomide) provided

3. ONE of the following: Gilenya® (fingolimod) § a. For Aubagio® and Gilenya®: quantity requested is ≤ 1 unit/day

b. For dimethyl fumarate: quantity requested is ≤ 2 tablets/day Tecfidera® (dimethyl 4. For Gilenya®, ONE of the following (weight may be taken over the fumarate) § phone if not documented on the PA request):

a. For Gilenya® 0.5 mg: weight ≥40 kg

b. For Gilenya® 0.25 mg: weight <40 kg

§ Brand Preferred over Notes: generic equivalents. In  general, MassHealth requires a trial of the  *Requests should clearly document the MS subtype. If the subtype is preferred drug or clinical not documented or unclear (e.g. diagnosis documented as ‘multiple rationale for prescribing sclerosis’ or ICD-10 G35), please outreach to the prescriber’s office the non-preferred drug to confirm the subtype. Clarification of diagnosis may be accepted generic equivalent. over the phone for CIS and RRMS only.  *For requests that document SPMS, active disease must be confirmed. Please refer to the appendix for additional information. If there is no documentation to confirm active SPMS, please forward to clinical review for case-by-case evaluation and prescriber outreach. Approval Criteria: Prescriber provides documentation of ALL of the following: 1. Appropriate diagnosis* Bafiertam® 2. Neurologist prescriber or consult notes from a neurology office (monomethyl fumarate) 3. Medical necessity for use instead of dimethyl fumarate AND Vumerity (diroximel fumarate) † 4. Requested quantity is ≤ 4 capsules/day

†Requests should generally be denied as there is no documented benefit of Bafiertam over dimethyl fumarate or Vumerity. If specific details are provided, please forward to clinical review for case-by-case evaluation. Approval Criteria: Prescriber provides documentation of ALL of the following:  Appropriate diagnosis* Mayzent® (siponimod)  Provider is a neurologist or consult notes from a neurology office are provided  Medical necessity for use instead of Gilenya® †  Inadequate response or adverse reaction to ONE or contraindication to ALL of the following disease modifying multiple sclerosis agents (History of claims is sufficient for all failed trials): a. Aubagio® (teriflunomide) b. glatiramer acetate therapy c. interferon therapy d. Ocrevus® (ocrelizumab) e. Tecfidera® (dimethyl fumarate) or Vumerity®(diroximel fumarate)  Genetic testing for CYP2C9 genotype showing the member does NOT have a CYP2C9 *3/*3 genotype  Requested dose is appropriate based on the CYP2C9 genotype‡

Notes:  * Requests should clearly document the MS subtype. If the subtype is not documented or unclear (e.g. diagnosis documented as ‘multiple sclerosis’ or ICD-10 G35), please outreach to the prescriber’s office to confirm the subtype. Clarification of diagnosis may be accepted over the phone for CIS and RRMS only.  * For requests that document SPMS, active disease must be confirmed. Please refer to the appendix for additional information. If there is no documentation to confirm active SPMS, please forward to clinical review for case-by-case evaluation and prescriber outreach.  †Requests that document need for first dose monitoring or potential for cardiac adverse events without additional details is generally not compelling rationale for use instead of Gilenya. If request documents need for first dose monitoring and/or provides details regarding cardiac adverse event concerns (e.g., underlying cardiac disease), please forward to clinical review for case-by-case evaluation.

 ‡Refer to the dosing table for information including dose titration schedule. Approval Criteria: Prescriber provides documentation of ALL of the following: 1. Appropriate diagnosis* Vumerity® (diroximel 2. Prescriber is a neurologist or consult notes from a neurology office fumarate) are provided 3. Medical necessity for use instead of dimethyl fumarate† 4. Requested quantity is ≤ 4 capsules/day

to confirm the subtype. Clarification of diagnosis may be accepted over the phone for CIS and RRMS only.  *For requests that document SPMS, active disease must be confirmed. Please refer to the appendix for additional information. If there is no documentation to confirm active SPMS, please forward to clinical review for case-by-case evaluation and prescriber outreach.  †Generally, an inadequate response or adverse reaction to dimethyl fumarate (Tecfidera®) would not be sufficient for approval. Please refer to the Appendix: Vumerity® medical necessity for additional considerations.

Approval Criteria: Prescriber provides documentation of ALL of the following: 1. Appropriate diagnosis* Zeposia® (ozanimod) 2. Provider is a neurologist or consult notes from a neurology office are provided 3. Medical necessity for use instead of Gilenya® † 4. Inadequate response or adverse reaction to ONE or contraindication to ALL of the following disease modifying multiple sclerosis agents (History of claims is sufficient for all failed trials): a. Aubagio® (teriflunomide) b. glatiramer acetate therapy c. interferon therapy d. Ocrevus® (ocrelizumab) e. Tecfidera® (dimethyl fumarate) or Vumerity®(diroximel fumarate) 5. Quantity requested is ≤ 1 unit/day

Notes:  *Requests should clearly document the MS subtype. If the subtype is not documented or unclear (e.g. diagnosis documented as ‘multiple sclerosis’ or ICD-10 G35), please outreach to the prescriber’s office to confirm the subtype. Clarification of diagnosis may be accepted over the phone for CIS and RRMS only.  *For requests that document SPMS, active disease must be confirmed. Please refer to the appendix for additional information. If there is no documentation to confirm active SPMS, please forward to clinical review for case-by-case evaluation and prescriber outreach.  †Requests that document need for first dose monitoring or potential for cardiac adverse events without additional details is generally not compelling rationale for use instead of Gilenya. If request documents need for first dose monitoring and/or provides details regarding cardiac adverse event concerns (e.g., underlying cardiac disease), please forward to clinical review for case-by-case evaluation. Brand Preferred over  In addition to any prior authorization requirements that may be Generic: listed above, generic medications listed below have Brand name products that are included on the MassHealth Brand Name Preferred Over Generic List. Requests for generic versions require a trial of the preferred drug or clinical rationale for prescribing the non-preferred drug generic equivalent prior to approval:

o dimethyl fumarate o fingolimod (placed on Brand preferred over Generic ahead of generic availability) o glatiramer acetate Denial Criteria: Cases that do not meet the approval criteria will be denied. If a request is denied and the prescriber has additional clinical documentation, a new prior authorization request must be submitted. Duration/Quantity of Prior authorization may be issued for 1 year Authorization: Recertification Criteria: For a diagnosis of PPMS and RRMS, resubmission by prescriber will infer a positive response to therapy and request can be recertified for up to 1 year.

For a diagnosis of SPMS, active disease must be confirmed. If active disease is confirmed, resubmission by prescriber will infer a positive response to therapy and request can be recertified for up to 1 year. If unable to confirm active disease, please forward to clinical review for case-by-case evaluation.

For a diagnosis of CIS, requests will be evaluated case-by-case. Please forward to clinical review.

Appendix: Stability

If a request documents that the member was previously covered on another insurance plan and the prescriber states stability, LCA criteria (excluding medical necessity criteria for Bafiertam, Mayzent, Vumerity, Zeposia) may be bypassed. Other applicable criteria should be met for the individual agent (e.g., diagnosis, dosing/QL, medical necessity, etc).

Requests documenting stability but not meeting other applicable criteria should be forwarded to clinical review for case- by-case evaluation.

Grandfathering

N/A

Requests above the quantity limit

There is limited/no data to support the use of MS DMTs above the established quantity limits. Requests should generally be denied lack of information (LOI). Compelling cases can be forwarded to clinical review for case-by-case evaluation.

Use of Combination Disease Modifying Therapy (DMT) in MS

Generally, use of combination DMT therapy in the treatment of MS is contraindicated or not recommended due to the potential for significant immune-related adverse events.

If a request for a new DMT is approved, the PA for the previously approved DMT should be end-dated.

Disease Modifying Therapy in Progressive MS

There is limited evidence to support the use of most MS agents in primary-progressive MS (PPMS) or non-active secondary-progressive MS (SPMS). Suggested treatments for PPMS are empiric, as they lack convincing clinical trial evidence of effectiveness. In SPMS, results of clinical trials have generally been negative; however, some study findings and clinical experience suggest that some treatments listed below have a modest benefit for patients with SPMS.

Primary-Progressive MS There is very limited evidence to support the use of any disease-modifying therapy in PPMS with the exception of ocrelizumab. Other potential treatment options for members with PPMS that have been evaluated in clinical trials include methylprednisolone monthly pulses, methotrexate, immune globulin (IVIG) or mitoxantrone.

If compelling rationale is provided (e.g., there is documentation/claims that show the member is stable on the requested agent, clinical literature is provided), please escalate to clinical review for case-by-case evaluation. At a minimum, members should be evaluated for an inadequate response, adverse reaction or contraindication to Ocrevus® (ocrelizumab) and medical necessity for use in PPMS.

Secondary-Progressive MS There is some data to support the use of disease-modifying therapy in active SPMS, particularly those with evidence of active disease by clinical or MRI measures. Although clinical studies evaluated most DMTs in RRMS, the FDA has approved these agents for all forms of relapsing MS, including active SPMS.

Active SPMS can be confirmed via the PA form, attached medical records or a letter of medical necessity. Please review all attached documentation with the request and review based on the following:  If there is documentation of a relapse in the previous two years  no CR consult required  If there is documentation of MRI-detected new lesion formation (without documentation of a relapse in the previous two years)  forward to clinical review for case-by-case evaluation.  If there is not clear documentation of active SPMS but the member recently (within the past one year) transitioned from RRMS to SPMS  forward to clinical review for case-by-case evaluation.

If the prescriber documents SPMS and there is no clear documentation supporting active disease and no medical records, please outreach to the office to let them know confirmation of active disease is required (e.g., recent relapse within the past two years).

Documentation is required for confirmation of active disease and a resubmission with this documentation is required (confirmation of active SPMS cannot be accepted over the phone, but if outreach is made, please document in the internal comment).

Vumerity® Medical Necessity

Inadequate response to Tecfidera® (dimethyl fumarate)  Requests documenting an IR to Tecfidera®  generally deny

Both Tecfidera® and Vumerity® are prodrugs of the same active metabolite. The efficacy of Vumerity® was based on clinical studies of Tecfidera®.

Contraindication to Tecfidera® (dimethyl fumarate)  Requests documenting a CI to Tecfidera®  generally deny.  If a CI is noted due to an ADR, see below.

Adverse Drug Reaction to Tecfidera® (dimethyl fumarate)  Request documents a GI-related ADR: o Limited details provided  deny o Detailed information is provided  approve or deny based on below

 Request documents any other (non-GI related [e.g., flushing]) ADRs  generally deny

The only noted difference in ADR profile between Vumerity® and Tecfidera® are GI-related effects (e.g., diarrhea, nausea, abdominal pain). However, the clinical benefit of this difference is unclear as the GI effects of Tecfidera® are generally considered mild and typically resolve within the first two months of treatment. Furthermore, similar rates of GI effects were observed with Vumerity® in an ongoing safety study (EVOLVE-MS-1) compared to real-world data of Tecfidera® (30.9% vs 27%, respectively). Of note, taking the medication with food can decrease the rate of GI upset. The overall discontinuation rate of Tecfidera® due to side effects were low in clinical studies.

Compelling information should be documented in the medical record or letter of medical necessity. Examples include:  Specific GI-related ADR(s) is/are documented (e.g., nausea, diarrhea)  Severity of the ADR must be documented (e.g., stools/day, N/V, disruption in ADLs, etc.)  Time of ADR onset relative to starting Tecfidera® should be clear and appropriate  GI ADR has not resolved despite at least two months of treatment with Tecfidera® (can consider shorter duration if ADR is severe and mitigation strategies have been used)  Member has used multiple mitigation strategies to alleviate GI ADRs (e.g., taking with food, use of anti-emetics or anti-diarrheals)

If you are uncertain if a request is compelling, please forward to clinical review for case-by-case evaluation.

Clinical Background Information and References

Original Approval Original Effective Policy Owner Approved by Date Date 12/1/2020 1/1/2021 Pharmacy Services Pharmacy & Therapeutics (P&T) Committee

Policy Revisions History

Revision Review Date Summary of Revisions Approved by Effective Date 12/1/2020 Retired policy 9.170 Multiple Sclerosis for 1/1/2021 P&T Committee MH. New Policy created to align with MH Unified Formulary Policy 1/19/2021 Updated policy to reflect PUF changes as 1/19/2021 P&T Committee of 10/30/20 2/4/2021 Updated policy to reflect 1.22.21 State 2/4/2021 P&T Committee policy changes. Updated to add Vumerity as an acceptable trial (Vumerity or dimethyl fumarate) for Mavenclad and Zeposia, verbiage changes to quantity limit appendix, verbiage change to provider being a neurologist/consult notes for all agents. 5/13/2021 Updated policy to reflect 2/19/21 changes 7/1/2021 P&T Committee from MH. Guideline updated to reflect

Policy Revisions History addition of Bafiertam and Vumerity which will both require PA. Updated policy to reflect 3/18/21 change (criteria 3) for Mayzent and Zeposia. Stability section also updated to reflect change.

Next Review Date 2021

Other Applicable Policies

Reference to Applicable Laws and Regulations, If Any

Disclaimer Information

Medical Policies are the Plan’s guidelines for determining the medical necessity of certain services or supplies for purposes of determining coverage. These Policies may also describe when a service or supply is considered experimental or investigational, or cosmetic. In making coverage decisions, the Plan uses these guidelines and other Plan Policies, as well as the Member’s benefit document, and when appropriate, coordinates with the Member’s health care Providers to consider the individual Member’s health care needs.

Plan Policies are developed in accordance with applicable state and federal laws and regulations, and accrediting organization standards (including NCQA). Medical Policies are also developed, as appropriate, with consideration of the medical necessity definitions in various Plan products, review of current literature, consultation with practicing Providers in the Plan’s service area who are medical experts in the particular field, and adherence to FDA and other government agency policies. Applicable state or federal mandates, as well as the Member’s benefit document, take precedence over these guidelines. Policies are reviewed and updated on an annual basis, or more frequently as needed. Treating providers are solely responsible for the medical advice and treatment of Members.

The use of this Policy is neither a guarantee of payment nor a final prediction of how a specific claim(s) will be adjudicated. Reimbursement is based on many factors, including member eligibility and benefits on the date of service; medical necessity; utilization management guidelines (when applicable); coordination of benefits; adherence with applicable Plan policies and procedures; clinical coding criteria; claim editing logic; and the applicable Plan – Provider agreement.