ModifiedCentenePolicy CP.PHAR.427

Siponimod (Mayzent) for relapsing forms of multiple sclerosis

Defines medical necessity, prior authorization, and continued therapy criteria for siponimod (Mayzent) in adults with relapsing forms of multiple sclerosis for Centene-affiliated health plans.

Policy Summary

PayerCentene

PolicySiponimod (Mayzent) for relapsing forms of multiple sclerosis

Policy CodePolicy CP.PHAR.427

Change TypeMaterial updates to approval duration, step therapy bypass (IL), and coverage exclusions

Effective Date09.01.19

Next Review DateN/A

Key ActionSubmit prior authorization with documentation showing patient meets all initial approval criteria, including CYP2C9 genotype and prior therapy history.

SourceLink

POLICY UPDATE CHANGES

Added step therapy bypass for Illinois HIM per IL HB 5395.

Extended initial approval duration from 6 to 12 months for this maintenance medication.

Primary progressive MS added to diagnoses/indications for which coverage is NOT authorized.

Requirements for documentation of baseline relapses/EDSS and specific measures of positive response were removed.

12 monthsApproval duration

2 mg/dayMax daily dose

CYP2C9*3/*3Contraindicated genotype

≥18

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

Coverage Criteria

inv-01: Initial Therapy — Multiple Sclerosis

Covered when ALL of the following are met for Initial Approval (Multiple Sclerosis):

Initial MS criteria: 1. Diagnosis of one of the following: (a) Clinically isolated syndrome, and member is contraindicated to both or has experienced significant adverse effects to an interferon-beta agent or glatiramer at up to maximally indicated doses; OR (b) Relapsing‑remitting MS, and failure of all of the following at up to maximally indicated doses unless clinically significant adverse effects are experienced or all are contraindicated: dimethyl fumarate; teriflunomide; fingolimod; and an interferon‑beta agent or glatiramer; OR (c) Secondary progressive MS.

For Illinois HIM requests, the step therapy requirements do not apply per IL HB 5395.

Prescriber and age: 2. Prescribed by or in consultation with a neurologist; 3. Age ≥ 18 years.

Genotype and concurrent therapy: 4. Documentation that member does not have a CYP2C9*3/*3 genotype; 5. Mayzent is not prescribed concurrently with other disease‑modifying therapies for MS.

Dosing: 6. Dose does not exceed 2 mg per day.<= 2 mg/day

Approval duration: 12 months

inv-02: Continuation Therapy — Multiple Sclerosis

Covered when ALL of the following are met for Continued Therapy (Multiple Sclerosis):

Eligibility for continued therapy: 1. Member meets one of the following: (a) Currently receiving medication via Centene benefit or member has previously met initial approval criteria; OR (b) Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations.

Response and concurrent therapy: 2. Member is responding positively to therapy; 3. Mayzent is not prescribed concurrently with other disease‑modifying therapies for MS.

Dose changes: 4. If request is for a dose increase, new dose does not exceed 2 mg per day.<= 2 mg/day

Approval duration: 12 months

Non‑FDA approved indications that are not specifically addressed within this policy are not authorized unless there is adequate supporting documentation of efficacy and safety in accordance with the applicable off‑label use policies: CP.CPA.09 (Commercial), HIM.PA.154 (HIM/ICHRA), or CP.PMN.53 (Medicaid), or other evidence of coverage documents.

When state Medicaid coverage provisions conflict with the coverage provisions in this clinical policy, state Medicaid coverage provisions take precedence. Refer to the applicable state Medicaid manual for specific coverage rules that may supersede this policy.

Use of siponimod (Mayzent) for primary progressive multiple sclerosis is explicitly not authorized / not medically necessary under this policy.

Coding and Dosing

inv-06: Maximum daily dose — 2 mg/day

Maximum daily dose2 mg/day

Titration schedule (general population)Day 1-2: 0.25 mg QD; Day 3: 0.5 mg QD; Day 4: 0.75 mg QD; Day 5: 1.25 mg QD; Day 6 onward: 2 mg QD

Dose limit for dose-increase requestsNew dose must not exceed 2 mg per day for continued therapy

inv-07: Dose for CYP2C9 *1/*3 or *2/*3 — 1 mg/day

Recommended maintenance dose for select CYP2C9 genotypesFor CYP2C9 *1/*3 or *2/*3 genotypes: Day 5 onward — 1 mg PO QD

Genotype impacts dosingCYP2C9 genotype affects siponimod exposure and requires dose adjustment for *1/*3 or *2/*3

Provider Actions and Operational Rules

Prior Authorization

Prior Authorization Required

Prior authorization is required. Provider must document that all initial approval criteria are met. Prior authorization may also be required for continuation of therapy.

Prior authorization may be required for all disease modifying therapies for MS.

Documentation Required

Required Supporting Documentation

Provider must submit documentation (such as office chart notes, lab results, or other clinical information) supporting that the member has met all approval criteria.

Step Therapy

Step Therapy for Relapsing‑Remitting MS

Background

Siponimod (Mayzent) is a sphingosine 1‑phosphate receptor modulator indicated for treatment of relapsing forms of multiple sclerosis, including clinically isolated syndrome, relapsing‑remitting MS, and active secondary progressive MS in adults. Metabolism is affected by CYP2C9 genotype, which influences dosing and contraindications.

Definitions

inv-17: Drug description — Siponimod (Mayzent)

Generic and brand nameSiponimod (Mayzent)

Drug classSphingosine 1-phosphate receptor modulator

Indication summaryIndicated for relapsing forms of multiple sclerosis (see policy for covered relapsing phenotypes)

inv-18: Genotype contraindication and dosing impact — CYP2C9*3/*3 genotype

Contraindicated genotypeCYP2C9*3/*3 — Mayzent is contraindicated in patients homozygous for CYP2C9*3

Dose adjustment requiredPatients with CYP2C9*1/*3 or *2/*3 require a reduced maintenance dose (1 mg QD)

Policy Summary

PayerCentene

PolicySiponimod (Mayzent) for relapsing forms of multiple sclerosis

Policy CodePolicy CP.PHAR.427

Change TypeMaterial updates to approval duration, step therapy bypass (IL), and coverage exclusions

Effective Date09.01.19

Next Review DateN/A

Key ActionSubmit prior authorization with documentation showing patient meets all initial approval criteria, including CYP2C9 genotype and prior therapy history.

SourceLink

On This Page

Monitoring implicationConfirm CYP2C9 genotype prior to initiating therapy to determine appropriate dosing

Step therapy applies for relapsing‑remitting multiple sclerosis: members must have failed (or have contraindications to) the following agents at up to maximally indicated doses before Mayzent will be approved: dimethyl fumarate (generic Tecfidera), teriflunomide (generic Aubagio), fingolimod (Gilenya), and an interferon‑beta agent (Avonex, Betaseron/Extavia, Rebif, or Plegridy) or glatiramer (Copaxone, Glatopa). For Illinois HIM requests, the step therapy requirements do not apply per IL HB 5395 (effective 1/1/2026) — a step therapy bypass for IL HIM has been added.

Affected products for step therapy: dimethyl fumarate (Tecfidera), teriflunomide (Aubagio), fingolimod (Gilenya), interferon‑beta agents (Avonex, Betaseron/Extavia, Rebif, Plegridy), glatiramer (Copaxone, Glatopa)
IL HIM: step therapy bypass per IL HB 5395 (effective 1/1/2026)

Denial Risk

Contraindicated Genotype / Excluded Diagnosis

Prescriptions for patients with a CYP2C9*3/*3 genotype or for the excluded diagnosis of primary progressive MS (when listed as an exclusion in the coverage criteria) are contraindications and are triggers for non‑coverage/denial. See Appendix C for full contraindication list.

Contraindicated genotype: CYP2C9*3/*3

Denial Risk

Medicaid Conflicts

When state Medicaid coverage provisions conflict with this clinical policy, the state Medicaid provisions take precedence and there may be a risk of denial if the member’s benefit is governed by state Medicaid rules.

Medicaid line of business may have differing coverage — state provisions prevail over this policy when in conflict.

Homozygous *3/*3 genotype causes substantially elevated siponimod plasma levels

inv-19: Primary progressive multiple sclerosis — Primary progressive MS added to section III to align with other MS agents.

Policy changePrimary progressive multiple sclerosis was added to Section III (diagnoses/indications not authorized)

Coverage implicationUse of siponimod for primary progressive MS is considered not authorized / not medically necessary under this policy

Alignment rationaleAdded to align with other multiple sclerosis agents per 2Q 2026 annual review