Subject: Zeposia SGM 3747-A P2025a

Drug

Zeposia

ZEPOSIA  (ozanimod)

Policy:

Indications

The indications below including FDA-approved indications and compendial uses are considered a covered benefit provided that all the approval criteria are met and the member has no exclusions to the prescribed therapy.

FDA-Approved Indications¹

• Treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.
• Treatment of moderately to severely active ulcerative colitis (UC) in adults.

All other indications are considered experimental/investigational and not medically necessary.

Documentation

Submission of the following information is necessary to initiate the prior authorization review:

Ulcerative Colitis (UC)

Continuation Requests

Chart notes or medical record documentation supporting positive clinical response to therapy or remission.

Prescriber Specialties

This medication must be prescribed by or in consultation with one of the following:

• Multiple sclerosis: neurologist
• Ulcerative colitis: gastroenterologist

Coverage Criteria

Relapsing Forms of Multiple Sclerosis (MS)^1,5

Authorization of 12 months may be granted to members who have been diagnosed with a relapsing form of multiple sclerosis (including relapsing-remitting and secondary progressive disease for those who continue to experience relapse).

Clinically Isolated Syndrome^1,5

Authorization of 12 months may be granted to members for the treatment of clinically isolated syndrome of multiple sclerosis.

Ulcerative Colitis¹

Authorization of 12 months may be granted for treatment of moderately to severely active ulcerative colitis.

Continuation of Therapy

Relapsing Forms of Multiple Sclerosis and Clinically Isolated Syndrome

Authorization of 12 months may be granted for all members (including new members) who achieve or maintain a positive clinical response as evidenced by experiencing disease stability or improvement while receiving Zeposia.

Ulcerative Colitis^3-4

Authorization of 12 months may be granted for all members (including new members) who are using the requested medication for moderately to severely active ulcerative colitis and who achieve or maintain remission.

Authorization of 12 months may be granted for all members (including new members) who are using the requested medication for moderately to severely active ulcerative colitis and who achieve or maintain a positive clinical response as evidenced by low disease activity or improvement in signs and symptoms of the condition when there is improvement in any of the following from baseline:

• Stool frequency
• Rectal bleeding
• Urgency of defecation
• C-reactive protein (CRP)
• Fecal calprotectin (FC)
• Appearance of the mucosa on endoscopy, computed tomography enterography (CTE), magnetic resonance enterography (MRE), or intestinal ultrasound
• Improvement on a disease activity scoring tool (e.g., Ulcerative Colitis Endoscopic Index of Severity [UCEIS], Mayo score)

Other Criteria

For all indications: Member cannot use the requested medication concomitantly with immunomodulators, biologic drugs, targeted synthetic drugs, or disease modifying multiple sclerosis agents for the same indication (Note: Ampyra and Nuedexta are not disease modifying).

For multiple sclerosis: Authorization may be granted for pediatric members less than 18 years of age when benefits outweigh risks.

Dosage and Administration

Approvals may be subject to dosing limits in accordance with FDA-approved labeling, accepted compendia, and/or evidence-based practice guidelines.

Place of Service:

Outpatient

The above policy is based on the following references:

1. Zeposia [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; August 2024.
2. Talley NJ, Abreu MT, Achkar J, et al. An evidence-based systematic review on medical therapies for inflammatory bowel disease. Am J Gastroenterol. 2011;106 Suppl 1:S2-S26.
3. Rubin DT, Ananthakrishnan AN, Siegel CA, et al. ACG Clinical Guideline Update: Ulcerative Colitis in Adults. Am J Gastroenterol. 2025;120(6):1187-1224.
4. Singh S, Loftus EV Jr, Limketkai BN, et al. AGA Living Clinical Practice Guideline on Pharmacological Management of Moderate-to-Severe Ulcerative Colitis. Gastroenterology. 2024;167(7):1307-1343.
5. Rae-Grant A, Day GS, Marrier RA, et al., Practice guideline recommendations summary: Disease-modifying therapies for adults with multiple sclerosis. Neurology. 2018;90(17):777-788.

Copyright Aetna Inc. All rights reserved. Pharmacy Clinical Policy Bulletins are developed by Aetna to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. This Clinical Policy Bulletin contains only a partial, general description of plan or program benefits and does not constitute a contract. Aetna does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Aetna or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. This Clinical Policy Bulletin may be updated and therefore is subject to change.

February 15, 2026