mhn ozanimod (Zeposia) Coverage Update

Coverage Criteria

Initial Therapy - Multiple Sclerosis

Covered when ALL of the following are met

MS Initial: 1. Diagnosis of one of the following: a) Clinically isolated syndrome (and member is contraindicated to or has experienced clinically significant adverse effects to an interferon‑beta agent or glatiramer), b) Relapsing‑remitting MS with failure of all of the following at up to maximally indicated doses unless intolerant or contraindicated: dimethyl fumarate, teriflunomide, fingolimod, and an interferon‑beta agent or glatiramer, or c) Secondary progressive MS; 2. Prescribed by or in consultation with a neurologist; 3. Age ≥ 18 years; 4. Not prescribed concurrently with other disease‑modifying therapies for MS; 5. Dose does not exceed 0.92 mg per day and 1 capsule per day.dose ≤ 0.92 mg/day

Prior authorization required for all disease modifying therapies for MS

Initial Therapy - Ulcerative Colitis (Medicaid only)

Covered when ALL of the following are met

UC Initial (Medicaid): 1. Diagnosis of ulcerative colitis; 2. Prescribed by or in consultation with a gastroenterologist; 3. Age ≥ 18 years; 4. Documentation of disease activity with a Mayo Score ≥ 6, modified Mayo Score ≥ 5, or Mayo Endoscopic Score ≥ 2; 5. Failure of an 8‑week trial of systemic corticosteroids unless contraindicated, intolerant, or previously failed a biologic agent; 6. Failure of one adalimumab product or one ustekinumab product used for ≥ 3 consecutive months unless clinically significant adverse effects are experienced or contraindicated; 7. Dose does not exceed 0.92 mg per day and 1 capsule per day.dose ≤ 0.92 mg/day

Continuation Therapy - Multiple Sclerosis

Covered when ALL of the following are met

MS Continuation: 1. Member currently receiving medication via Centene benefit or has previously met initial approval criteria (or continuity of care applies); 2. Member is responding positively to therapy; 3. Zeposia is not prescribed concurrently with other disease‑modifying therapies for MS; 4. If request is for a dose increase, new dose does not exceed 0.92 mg per day and 1 capsule per day.

Approval duration: 12 months

Continuation Therapy - Ulcerative Colitis (Medicaid only)

Covered when ALL of the following are met

UC Continuation (Medicaid): 1. Member currently receiving medication via Centene benefit or has previously met initial approval criteria (or continuity of care applies); 2. Member is responding positively to therapy; 3. If request is for a dose increase, new dose does not exceed 0.92 mg per day and 1 capsule per day.

Approval duration: 12 months

General coverage criteria (dosing and approval duration)

Covered when dosing and indication-specific criteria are met; approval durations updated per 2026 review

Dosing and administration: Initiate with titration: Days 1–4: 0.23 mg PO QD; Days 5–7: 0.46 mg PO QD; Day 8 and thereafter: 0.92 mg PO QD. For mild or moderate hepatic impairment (Child‑Pugh A or B) give every‑other‑day dosing. If a dose is missed during the first 2 weeks, reinitiate titration; if missed after the first 2 weeks, continue as planned.max 0.92 mg/day

From dosing section

Approval duration: Initial and continued approvals for maintenance therapy are set to 12 months per 2Q 2026 update.12 months

Policy change

Coverage is not authorized for primary progressive multiple sclerosis. This diagnosis is listed among the indications for which ozanimod (Zeposia) is excluded from coverage and should not be approved under this policy.

For members covered by Medicaid, state Medicaid coverage provisions take precedence when they conflict with this clinical policy. Providers and reviewers must follow applicable state Medicaid manuals and guidance for any differing coverage rules or exclusions.

Non–FDA‑approved (off‑label) indications that are not specifically addressed in this policy are not authorized unless the provider supplies sufficient documentation of efficacy and safety in accordance with the applicable off‑label use policies: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace/ICHRA, or CP.PMN.53 for Medicaid, or unless coverage is supported by evidence of coverage documents.

Initial Therapy

Initial therapy — Initial authorization criteria by indication

Initial authorization criteria by indication

MS - Initial authorization: See Initial Therapy - Multiple Sclerosis: diagnosis subtype, neurologist prescriber or consult, age ≥ 18, required prior therapy failures for relapsing‑remitting MS unless contraindicated or intolerant, not concurrent with other DMTs, dosing limit 0.92 mg/day and 1 capsule/day.

UC (Medicaid) - Initial authorization: See Initial Therapy - Ulcerative Colitis (Medicaid only): UC diagnosis, gastroenterologist prescriber or consult, age ≥ 18, required Mayo/modified Mayo/Mayo Endoscopic Score documentation, failure of systemic corticosteroids (8 weeks) unless contraindicated, and failure of one adalimumab or one ustekinumab product used ≥ 3 months unless contraindicated or intolerant; dosing limit 0.92 mg/day and 1 capsule/day.

Initial therapy dosing — Initiation dosing and reinitiation rules

Initiation dosing and reinitiation rules

Continuation and Continued Therapy

Continuation — Continuation therapy requirements

Continuation therapy requirements

Continuation: Member is currently receiving medication via Centene benefit or previously met initial approval criteria (or continuity of care applies); member is responding positively to therapy; dosing limits apply; approval duration: 12 months.

Continued therapy — Criteria and duration for continued therapy

Criteria and duration for continued therapy

Continued therapy duration: Continued approval duration standardized to 12 months for ongoing treatment regardless of prior total treatment duration.

2Q 2025–2026 updates

Provider Actions and Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required for all disease modifying therapies for multiple sclerosis (MS). Prior authorization requests must document prior therapies tried, specialist consultation, and supporting clinical information. Approval durations: initial and continued therapy approvals are issued for up to 12 months for maintenance therapy.

Prior authorization required for all disease modifying therapies for MS
Approval duration for continued therapy: 12 months

Documentation Required

Required Documentation

Provider must submit documentation (such as office chart notes, laboratory results, imaging, endoscopy reports, Mayo scores, and other clinical information) supporting that the member meets all approval criteria. Lack of sufficient documentation that the member has met all criteria may lead to denial of the request.

Examples: office notes, labs, endoscopy reports, Mayo or modified Mayo Score, prior treatment records

Step Therapy Rules

Step	Required prior agents / conditions	Notes
1	Multiple sclerosis (relapsing‑remitting): documented failure of all of the following at up to maximally indicated doses unless clinically significant adverse effects or contraindications: dimethyl fumarate; teriflunomide; fingolimod; and an interferon‑beta agent or glatiramer	Prior authorization required for all disease‑modifying therapies for MS; prescriber must be or consult with a neurologist; age ≥ 18; dose limit 0.92 mg/day (1 capsule/day).
2	Clinically isolated syndrome: contraindication to both or clinically significant adverse effects to an interferon‑beta agent and glatiramer at maximally indicated doses	If criteria met, may qualify for initial approval per MS initial criteria; dosing/titration per dosing regimen.
3	Ulcerative colitis (Medicaid only): failure of an 8‑week trial of systemic corticosteroids unless contraindicated or previously failed a biologic agent; plus failure of one adalimumab product or one ustekinumab product used ≥3 consecutive months unless intolerant or contraindicated	Documentation of Mayo Score ≥6, modified Mayo ≥5, or Mayo Endoscopic Score ≥2 required; prior authorization may be required for adalimumab/ustekinumab products; age ≥18; gastroenterologist prescriber or consult.

Step	UC step therapy rule / preferred products	Bypass or special conditions
1	Initial requirement: documentation of failure of systemic corticosteroids (8‑week trial) unless contraindicated, plus failure of one adalimumab product or one ustekinumab product used ≥3 months	Examples of preferred adalimumab and preferred ustekinumab/Stelara biosimilars have been updated across reviews (preferred adalimumab examples include Hadlima, Simlandi, Yusimry, adalimumab‑aaty, adalimumab‑adaz, adalimumab‑adbm, adalimumab‑fkjp; preferred Stelara biosimilars include Otulfi, Pyzchiva, Selarsdi, Steqeyma, Yesintek).
2	Policy modifications: redirections to preferred adalimumab products were removed per 2024 AGA guidance, then preferred adalimumab and Stelara biosimilar lists were again added in later updates	References and preferred‑product examples have changed over multiple updates; reviewers should apply the current preferred‑product list in Appendix B when applicable.
3	Bypass condition: if member has failed a biologic agent, the policy allows bypass of conventional therapy step (i.e., do not step back from biologic to conventional therapy)	State‑specific exceptions: Illinois HIM step therapy bypasses apply per IL HB 5395 (step therapy requirements do not apply for IL HIM requests as of 1/1/2026).

Coding

Codes referencedmixed

none listed

No explicit CPT/HCPCS/ICD-10/NDC codes provided in this part of the document

Mayo / modified Mayo / Mayo Endoscopic Score — Policy thresholds

Mayo ScoreOverall score 0–12 based on stool frequency, rectal bleeding, endoscopy, and physician global assessment; policy threshold: ≥ 6

Modified Mayo ScoreThree-parameter score (stool frequency, rectal bleeding, endoscopy) with maximum 9; policy threshold: ≥ 5

Mayo Endoscopic ScoreEndoscopic severity 0–3; policy threshold: ≥ 2 (score of 2 indicates moderate-to-severe inflammation)

Dose and approval duration thresholds

Maximum daily dose0.92 mg per day (maximum dose for all indications)

Quantity per day1 capsule per day (policy dosing limit)

Quantity Limits

Ozanimod (Zeposia) — Quantity limits and key facts

Daily capsule limit1 capsule per day

Maximum daily milligram limit0.92 mg/day

Available capsule strengths0.23 mg, 0.46 mg, 0.92 mg

Initiation titrationDays 1–4: 0.23 mg QD; Days 5–7: 0.46 mg QD; Day 8+: 0.92 mg QD

Reinitiation after missed dosesIf missed during first 2 weeks, reinitiate titration; if missed after 2 weeks, continue as planned

Zeposia (ozanimod) — Maximum dose

Maximum daily dose (mg)

Definitions

Mayo Score / Modified Mayo / Mayo Endoscopic Score — Use and thresholds

PurposeTools to evaluate ulcerative colitis activity used in policy determinations

Policy thresholdsMayo Score ≥ 6, modified Mayo Score ≥ 5, or Mayo Endoscopic Score ≥ 2

Score interpretationMayo Endoscopic Score: 0–3 with 2 = moderate disease; Modified Mayo max = 9; Mayo max = 12

Moderate-to-severe ulcerative colitis — Policy definitions

Policy definition for moderate-to-severe UCMayo Endoscopic Score > 2 or modified Mayo Score ≥ 5 may be used to define moderate-to-severe UC per updates

Alternate threshold in initial criteriaPolicy initial criteria require documentation of Mayo Score ≥ 6, modified Mayo ≥ 5, or Mayo Endoscopic Score ≥ 2

Background

Ozanimod (Zeposia) is a sphingosine 1‑phosphate receptor modulator approved for relapsing forms of multiple sclerosis and for moderately to severely active ulcerative colitis in adults. The product is available as capsules in multiple strengths and is used as a disease‑modifying therapy for MS and as a treatment option for UC when the applicable clinical criteria are met.

Biosimilar / Preferred Product Notes

Billing Rule

Policy records multiple updates to UC preferred biologic/biosimilar lists

The policy notes multiple updates to preferred biologic and biosimilar lists for UC (including adalimumab product examples and preferred Stelara biosimilars), with examples added and removed across revisions.

Examples of preferred adalimumab products and preferred Stelara biosimilars were added/removed in successive updates (see policy change log)

OpenPayer

Ozanimod (Zeposia) — Clinical Policy

Coverage Criteria

Initial Therapy

Continuation and Continued Therapy

Provider Actions and Requirements

Step Therapy Rules

Coding

Quantity Limits

Definitions

Background

Biosimilar / Preferred Product Notes