Clinical Policy: Inebilizumab-cdon (Uplizna) Form

CENTENE Corporation

Clinical Policy: Inebilizumab-cdon (Uplizna) Reference Number: CP.PHAR.458 Effective Date: 06.11.20 Last Review Date: 08.25 Line of Business: Commercial, HIM, Medicaid

Coding Implications Revision Log

See Important Reminder at the end of this policy for important regulatory and legal information.

Description Inebilizumab-cdon (Uplizna®) is an anti-CD19-directed cytolytic antibody.

FDA Approved Indication(s) Uplizna is indicated for the treatment of:

• Neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive
• Immunoglobulin G4-related disease (IgG4-RD) in adult patients
• Generalized myasthenia gravis (gMG) in adult patients who are antiacetylcholine receptor (AChR) or anti-muscle specific tyrosine kinase (MuSK) antibody positive

Policy/Criteria

11. Dose does not exceed a loading dose of 300 mg on Day 1 and Day 15, followed by 300 mg every 6 months starting 6 months after the first infusion.

Approval duration: Medicaid/HIM – 12 months Commercial – 6 months or to the member’s renewal date, whichever is longer

B. Immunoglobulin G4-Related Disease (must meet all):

1. Diagnosis of IgG4-RD;
3. Dose does not exceed a loading dose of 300 mg on Day 1 and Day 15, followed by 300 mg every 6 months starting 6 months after the first infusion.

Approval duration: Medicaid/HIM – 12 months Commercial – 6 months or to the member’s renewal date, whichever is longer

C. Generalized Myasthenia Gravis (must meet all):

1. Diagnosis of gMG;
2. Prescribed by or in consultation with a neurologist;
3. Age ≥ 18 years;
5. Dose does not exceed a loading dose of 300 mg on Day 1 and Day 15, followed by 300 mg every 6 months starting 6 months after the first infusion.

Approval duration: Medicaid/HIM – 12 months Commercial – 6 months or to the member’s renewal date, whichever is longer

D. Other diagnoses/indications (must meet 1 or 2):

1. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or
2. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.

II. Continued Therapy A. Neuromyelitis Optica Spectrum Disorder (must meet all):

1. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; b. Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B);
3. If request is for a dose increase, new dose does not exceed 300 mg every 6 months.

Approval duration: Medicaid/HIM – 12 months Commercial – 6 months or to the member’s renewal date, whichever is longer

B. Immunoglobulin G4-Related Disease (must meet all):

1. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; b. Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B);
3. If request is for a dose increase, new dose does not exceed 300 mg every 6 months.

Approval duration: Medicaid/HIM – 12 months Commercial – 6 months or to the member’s renewal date, whichever is longer

C. Generalized Myasthenia Gravis (must meet all):

1. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; b. Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B);
3. If request is for a dose increase, new dose does not exceed 300 mg every 6 months.

Approval duration: Medicaid/HIM – 12 months Commercial – 6 months or to the member’s renewal date, whichever is longer

D. Other diagnoses/indications (must meet 1 or 2):

1. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or
2. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.

III.Diagnoses/Indications for which coverage is NOT authorized: A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off label use policies – CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid, or evidence of coverage documents.

IV.Appendices/General Information Appendix A: Abbreviation/Acronym Key AChR: acetylcholine receptor ACR: American College of Rheumatology AQP-4: aquaporin-4 EDSS: expanded disability status scale EULAR: European League Against Rheumatism FDA: Food and Drug Administration gMG: generalized myasthenia gravis IgG4-RD: immunoglobulin G4-related disease MG-ADL: Myasthenia Gravis-Activities of Daily Living MGFA: Myasthenia Gravis Foundation of America MuSK: muscle specific tyrosine kinase NMOSD: neuromyelitis optica spectrum disorder

Appendix B: Therapeutic Alternatives This table provides a listing of preferred alternative therapy recommended in the approval criteria. The drugs listed here may not be a formulary agent for all relevant lines of business and may require prior authorization.

| Drug Name | Dosing Regimen | Dose Limit/

Maximum Dose |

|-----------|---------------|----------------|

| Rituxan® (rituximab), Riaubn™ (rituximab-

arrx), Ruxience™ (rituximab-pvvr) | NMOSD: IV: 375 mg/m² per week for 4 weeks as induction, followed by 375 mg/m² biweekly every 6 to 12 months | See regimen |

| Truxima® (rituximab-

abs)* | | |

| Corticosteroids for gMG | | |

| betamethasone | Oral: 0.6 to 7.2 mg PO per day | 7.2 mg/day |

| dexamethasone | Oral: 0.75 to 9 mg/day PO | 9 mg/day |

| methylprednisolone | Oral: 12 to 20 mg PO per day; increase as needed by 4 mg every 2-3 days until there is marked clinical improvement | 40 mg/day |

| prednisone | Oral: 15 mg/day to 20 mg/day; increase by 5 mg every 2-3 days as needed | 60 mg/day |

| Cholinesterase Inhibitors for gMG | | |

| pyridostigmine (Mestinon®) | Oral immediate-release: 600 mg daily in divided doses (range, 60-1,500 mg daily in divided doses)<br>Oral sustained release: 180-540 mg QD or BID | Immediate-

release: 1,500 mg/day<br>Sustained- release:1,080 mg/day |

| neostigmine (Bloxiverz®) | Oral: 15 mg TID. The daily dosage should be gradually increased at intervals of 1 or more days. The usual maintenance dosage is 15-375 mg/day (average 150 mg)<br>IM or SC: 0.5 mg based on response to therapy | Oral: 375 mg/day |

| Nonsteroidal Immunosuppressants for gMG | | |

| azathioprine (Imuran®) | Oral: 50 mg QD for 1 week, then increase gradually to 2 to 3 mg/kg/day | 3 mg/kg/day |

| mycophenolate mofetil (Cellcept®)* | Oral: Dosage not established. 1 gram BID has been used with adjunctive corticosteroids or other non-steroidal immunosuppressive medications | 2 g/day |

| cyclosporine (Sandimmune®)* | Oral: initial dose of cyclosporine (non-modified), 5 mg/kg/day in 2 divided doses | 5 mg/kg/day |

| Rituxan® (rituximab), Riaubn™ (rituximab-

arrx), Ruxience™ (rituximab-pvvr), Truxima® (rituximab- abs)* | IV: 375 mg/m² once a week for 4 weeks; an additional 375 mg/m² dose may be given every 1 to 3 months afterwards | 375 mg/m² |

Therapeutic alternatives are listed as Brand name® (generic) when the drug is available by brand name only and generic (Brand name®) when the drug is available by both brand and generic. Off-label

Appendix C: Contraindications/Boxed Warnings

• Contraindication(s): previous life-threatening reaction to infusion of Uplizna, active hepatitis B infection, active or untreated latent tuberculosis
• Boxed warning(s): none reported

Appendix D: General Information

• AQP-4-IgG-seropositive status is confirmed with the use of commercially available cell- binding kit assay (Euroimmun).
• The MG-ADL scale is an 8-item patient-reported scale that measures functional status in 8 domains related to MG – talking, chewing, swallowing, breathing, impairment of ability to brush teeth or comb hair, impairment of ability to arise from a chair, double vision, and eyelid droop. Each domain is given a score of 0-3, with 0 being normal and 3 being most severe impairment. A 2-point decrease in the MG-ADL score is considered a clinically meaningful response.
• ACR/EULAR IgG4-RD classification criteria (all of the following):
  • Meets entry requirements:
    • Characteristic clinical or radiologic involvement of a typical organ (e.g., pancreas, salivary glands, bile ducts, orbits, kidney, lung, aorta, retroperitoneum, pachymeninges, or thyroid gland (Riedel’s thyroiditis) OR
    • Pathologic evidence of an inflammatory process accompanied by a lymphoplasmacytic infiltrate of uncertain etiology in one of these same organs
  • Does NOT meet any of the classification criteria exclusions:
    • Fever
    • No objective response to glucocorticoids
    • Leukopenia and thrombocytopenia with no explanation
    • Peripheral eosinophilia
    • Positive antineutrophil cytoplasmic antibody (specifically against proteinase 3 or myeloperoxidase)
    • Positive SSA/Ro or SSB/La antibody
    • Positive double-stranded DNA, RNP, or Sm antibody
    • Other disease-specific autoantibody
    • Cryoglobulinemia
    • Known radiologic findings suspicious for malignancy or infection that have not been sufficiently investigated
    • Rapid radiologic progression
    • Long bone abnormalities consistent with Erdheim-Chester disease
    • Splenomegaly
    • Cellular infiltrates suggesting malignancy that have not been sufficiently evaluated
    • Markers consistent with inflammatory myofibroblastic tumor
    • Prominent neutrophilic inflammation
    • Necrotizing vasculitis
    • Prominent necrosis
    • Primarily granulomatous inflammation
    • Pathologic features of macrophage/histiocytic disorder
• Multicentric Castleman’s disease
• Crohn’s disease or ulcerative colitis (if only pancreatobiliary disease is present)
• Hashimoto thyroiditis (if only the thyroid is affected)
• Achieves ≥ 20 classification criteria inclusion points:

V. Dosage and Administration

VI. Product Availability Solution for injection in a single-dose vial: 100 mg/10 mL

VII. References

1. Uplizna Prescribing Information. Gaithersburg, MD: Viela Bio, Inc.; December 2025. Available at: https://www.uplizna.com. Accessed December 16, 2025.
2. Cree BA, Bennett JL, Kim HJ, et al. Inebilizumab for the treatment of neuromyelitis optica spectrum disorder (N-Momentum): A double-blind, randomised placebo-controlled phase 2/3 trial. Lancet. 2019; 394(10206): P1352-1363.
3. Sellner J, Boggild M, Clanet M, et al. EFNS guidelines on diagnosis and management of neuromyelitis optica. European Journal of Neurology. 2010; 17: 1019–1032.
4. Kumpft T, Giglhuber K, Aktas O, et al. Update on the diagnosis and treatment of neuromyelitis optica spectrum disorders (NMOSD) – revised recommendations of the Neuromyelitis Optica Study Group (NEMOS). Part II: Attack therapy and long-term management. Journal of Neurology. 2023; 271: 141-176.
5. Stone JH, Khosroshahi A, Zhang W, et al. Inebilizumab for treatment of IgG4-related disease. N Engl J Med. 2025; 392(12): 1168-1177.
6. Wallace ZS, Naden RP, Chari S, et al. The 2019 American College of Rheumatology/European League Against Rheumatism classification criteria for IgG4-related disease. Arthritis Rheumatol. 2020; 72(1): 7-19.
7. Khosroshahi A, Wallace Z, Crowe J, et al. International consensus guidance statement on the management and treatment of IgG4-related disease. Arthritis Rheumatol. 2015; 67(7): 1688-1699.
8. Nowak RJ, Benatar M, Ciafaloni E, et al. A phase 3 trial of inebilizumab in generalized myasthenia gravis. N Engl J Med. 2025; 392(23): 2309-2320.
9. Sanders DB, Wolfe GI, Benatar M, et al. International consensus guidance for management of myasthenia gravis. Neurology. 2016; 87(4): 419-425.
10. Narayanaswami P, Sanders DB, Wolfe G, et al. International consensus guidance for management of myasthenia gravis. Neurology. 2020; 96(3): 114-122.
11. Treatment strategy. Myasthenia Gravis Foundation of America. Available at: https://myasthenia.org/Newly-Diagnosed/Treatment-Strategy. Accessed December 16, 2025.
12. Muppidi S, Silvestri N, Tan U, et al. The evolution of Myasthenia Gravis-Activities of Daily Living (MG-ADL) scale utilization to measure myasthenia gravis symptoms and treatment response (1817). Neurology. 2021; 96(15 Suppl): 1817.

Coding Implications Codes referenced in this clinical policy are for informational purposes only. Inclusion or exclusion of any codes does not guarantee coverage. Providers should reference the most up-to- date sources of professional coding guidance prior to the submission of claims for reimbursement of covered services.

Reviews, Revisions, and Approvals

CLINICAL POLICY Inebilizumab-cdon

Important Reminder This clinical policy has been developed by appropriately experienced and licensed health care professionals based on a review and consideration of currently available generally accepted standards of medical practice; peer-reviewed medical literature; government agency/program approval status; evidence-based guidelines and positions of leading national health professional organizations; views of physicians practicing in relevant clinical areas affected by this clinical policy; and other available clinical information. The Health Plan makes no representations and accepts no liability with respect to the content of any external information used or relied upon in developing this clinical policy. This clinical policy is consistent with standards of medical practice current at the time that this clinical policy was approved. “Health Plan” means a health plan that has adopted this clinical policy and that is operated or administered, in whole or in part, by Centene Management Company, LLC, or any of such health plan’s affiliates, as applicable.

The purpose of this clinical policy is to provide a guide to medical necessity, which is a component of the guidelines used to assist in making coverage decisions and administering benefits. It does not constitute a contract or guarantee regarding payment or results. Coverage decisions and the administration of benefits are subject to all terms, conditions, exclusions, and limitations of the coverage documents (e.g., evidence of coverage, certificate of coverage, policy,

contract of insurance, etc.), as well as to state and federal requirements and applicable Health Plan-level administrative policies and procedures.

This clinical policy is effective as of the date determined by the Health Plan. The date of posting may not be the effective date of this clinical policy. This clinical policy may be subject to applicable legal and regulatory requirements relating to provider notification. If there is a discrepancy between the effective date of this clinical policy and any applicable legal or regulatory requirement, the requirements of law and regulation shall govern. The Health Plan retains the right to change, amend or withdraw this clinical policy, and additional clinical policies may be developed and adopted as needed, at any time.

This clinical policy does not constitute medical advice, medical treatment, or medical care. It is not intended to dictate to providers how to practice medicine. Providers are expected to exercise professional medical judgment in providing the most appropriate care, and are solely responsible for the medical advice and treatment of members. This clinical policy is not intended to recommend treatment for members. Members should consult with their treating physician in connection with diagnosis and treatment decisions.

Providers referred to in this clinical policy are independent contractors who exercise independent judgment and over whom the Health Plan has no control or right of control. Providers are not agents or employees of the Health Plan.

This clinical policy is the property of the Health Plan. Unauthorized copying, use, and distribution of this clinical policy or any information contained herein are strictly prohibited. Providers, members, and their representatives are bound to the terms and conditions expressed herein through the terms of their contracts. Where no such contract exists, providers, members and their representatives agree to be bound by such terms and conditions by providing services to members and/or submitting claims for payment for such services.

Note: For Medicaid members, when state Medicaid coverage provisions conflict with the coverage provisions in this clinical policy, state Medicaid coverage provisions take precedence. Please refer to the state Medicaid manual for any coverage provisions pertaining to this clinical policy.

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