The purpose of this policy is to provide general information applicable to the administration of health benefits that Horizon Blue Cross Blue Shield of New Jersey and Horizon Healthcare of New Jersey, Inc. (collectively “Horizon BCBSNJ”) insures or administers. If the member’s contract benefits differ from the medical policy, the contract prevails. Although a service, supply or procedure may be medically necessary, it may be subject to limitations and/or exclusions under a member’s benefit plan. If a service, supply or procedure is not covered and the member proceeds to obtain the service, supply or procedure, the member may be responsible for the cost. Decisions regarding treatment and treatment plans are the responsibility of the physician. This policy is not intended to direct the course of clinical care a physician provides to a member, and it does not replace a physician’s independent professional clinical judgment or duty to exercise special knowledge and skill in the treatment of Horizon BCBSNJ members. Horizon BCBSNJ is not responsible for, does not provide, and does not hold itself out as a provider of medical care. The physician remains responsible for the quality and type of health care services provided to a Horizon BCBSNJ member.
Horizon BCBSNJ medical policies do not constitute medical advice, authorization, certification, approval, explanation of benefits, offer of coverage, contract or guarantee of payment.
Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disease of the central nervous system characterized by inflammatory lesions in the optic nerves and spinal cord, causing a continual and significant decrease in quality of life due to permanent neurologic disorders. Patients with NMOSD frequently experience a relapsing disease course with repeated attacks leading to accumulating neurological damage and disability. Symptoms may include visual impairment, motor disability, and loss of quality of life. Patients also can lose bladder and bowel control, suffer nerve pain and experience respiratory failure. In some cases, attacks of NMOSD result in death. It affects approximately 10,000 patients in the United States. Approximately 80% of patients who have NMOSD have anti-aquaporin-4 (AQP4) antibodies.
The standard of care has been long-term immunotherapy to prevent the attacks; however, Soliris (eculizumab) was approved in June 2019 for patients with NMOSD who are anti-aquaporin-4 (AQP4) antibody positive. Soliris is given intravenously every 2 weeks.
On June 11, 2020, the FDA approved Viela Bio’s Uplizna (inebilizumab-cdon) intravenous injection for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive. Uplizna has Orphan Drug status and is designated as a Breakthrough Therapy.
The effectiveness of Uplizna for the treatment of NMOSD was demonstrated in a clinical study (N-MOMENTUM, NCT02200770) of 230 adult patients that evaluated the efficacy and safety of intravenous Uplizna. In the trial, 213 of the 230 patients were anti-aquaporin-4 (AQP4) antibody positive. During the 197-day study, the risk of an NMOSD relapse in the 161 anti-AQP4 antibody positive patients who were treated with Uplizna was reduced by 77% when compared to the placebo treatment group. There was no evidence of a benefit in patients who were anti-AQP4 antibody negative. In addition, 89% of these patients remained relapse-free six months after treatment compared to 58% in the placebo group. Uplizna is given as 300mg by intravenous infusion on days 1 and 15, and then every 6 months.
The prescribing information for Uplizna includes a warning for infusion reactions, potential depletion of certain proteins (hypogammaglobulinemia), and potential increased risk of infection – including Progressive Multifocal Leukoencephalopathy, and potential reactivation of hepatitis B and tuberculosis. The most common adverse reactions in the NMOSD clinical trial were urinary tract infection, headache, joint pain (arthralgia), nausea and back pain. As per the package insert, women who are pregnant should not take Uplizna because it may cause harm to a developing fetus or newborn baby. The FDA advises health care professionals to inform females of reproductive age to use effective contraception during treatment with Uplizna and for six months after the last dose. As per the package insert, vaccination with live-attenuated or live vaccines is not recommended during treatment and should be administered at least four weeks prior to initiation of Uplizna.
Uplizna, a humanized CD19-directed monoclonal antibody, is administered as an intravenous (IV) infusion over 90 minutes. As per the package insert, patients should be pre-treated with a corticosteroid, an antihistamine and an anti-fever medication to reduce the risk of infusion-related reactions. The recommended initial dose is 300mg followed two weeks later by a second 300mg infusion. Starting six months after the initial infusion, maintenance doses of 300mg by IV infusion should be given every six months.
(NOTE: For Medicare Advantage, please refer to the Medicare Coverage Section below for coverage guidance.)
I. Inebilizumab-cdon (Uplizna) is considered medically necessary for the following FDA-approved indications:
A. Treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive who meet ALL of the following criteria:
- Member is 18 years of age or older
- Member has been screened for hepatitis B virus (HBV), quantitative serum immunoglobulins, and tuberculosis (TB) prior to initiating treatment
- Member does not have an active infection
- Member is not concomitantly receiving therapy with other immunosuppressant type drugs (i.e., alemtuzumab, natalizumab, cyclosporine, methotrexate, mitoxantrone, cyclophosphamide, tocilizumab, maintenance corticosteroids (not including pre-medications or rescue therapy, or doses of 20 mg or less a day), etc.)
- Member will not be using in combination with complement-inhibitor (i.e., eculizumab, ravulizumab) or anti-CD20-directed antibody (i.e., rituximab) therapies
- Member has history of one or more relapses that required rescue therapy within the year prior to screening, or 2 or more relapses that required rescue therapy in 2 years prior to screening
- Member has an Expanded Disability Status Scale (EDSS) score ≤ 7.5. Patients with an EDSS score of 8.0 are eligible if they are deemed capable of participating
II. When inebilizumab-cdon (Uplizna) is considered medically necessary, therapy will be approved at the following FDA recommended doses for an initial duration of 6 months:
A. Initial dose: 300 mg IV infusion, followed by 2 weeks later a second 300 mg IV infusion
III. At the end of the initial 6 month period, inebilizumab-cdon (Uplizna) will be continued and approved annually, subject to the following criteria:
B. Subsequent doses (starting 6 months from the first infusion): single 300 mg IV infusion every 6 months
[INFORMATIONAL NOTE: As per the FDA labeled package insert dosing section:
• Hepatitis B virus, quantitative serum immunoglobulins, and tuberculosis screening is required before the first dose
• Prior to every infusion:
o Determine if there is an active infection
• UPLIZNA must be diluted in 250 mL of 0.9% Sodium Chloride Injection, USP prior to administration
o Premedicate with a corticosteroid, an antihistamine, and an antipyretic
• UPLIZNA is administered as an intravenous infusion titrated to completion, approximately 90 minutes.
• Monitor patients closely during the infusion and for at least one hour after completion of the infusion.]
A. There is absence of unacceptable toxicity from the drug (e.g.: serious infusion reactions, serious systemic infections, etc.) AND
IV. Other uses of inebilizumab-cdon (Uplizna) are considered investigational.
B. Member responds to therapy as demonstrated by stabilization of disease or improvement in any of the following symptoms:
1. Reduction in relapses
2. Reduction of hospitalizations,
3. Improvement in EDSS
4. Reduction in plasma exchange treatments
There is no National Coverage Determination (NCD) for Inebilizumab-cdon (Uplizna). In the absence of an NCD, coverage decisions are left to the discretion of Local Medicare Carriers. Novitas Solutions, Inc, the Local Medicare Carrier for jurisdiction JL, has not issued a determination specific to this drug. Therefore, Medicare Advantage Products will follow the Horizon BCBSNJ Medical Policy. Local Coverage Article: Approved Drugs and Biologicals; Includes Cancer Chemotherapeutic Agents (A53049) also applies. Available at: https://www.cms.gov/medicare-coverage-database/details/article-details.aspx?articleId=53049&ver=44&name=314*1&UpdatePeriod=711&bc=AQAAEAAAAAAAAA%3d%3d&.
Horizon BCBSNJ Medical Policy Development Process:
This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.
1. Uplizna (inebilizumab-cdon) [package insert]. Viela Bio, Inc. Gaithersburg, MD. June 2020.
2. FDA Approves New Therapy for Rare Disease Affecting Optic Nerve, Spinal Cord. U.S. Food & Drug Administration. June 11, 2020. Available at: https://www.fda.gov/news-events/press-announcements/fda-approves-new-therapy-rare-disease-affecting-optic-nerve-spinal-cord?utm_campaign=FDA%20Approves%20New%20Therapy%20for%20Rare%20Disease%20Affecting%20Optic%20Nerve%20and%20Spinal%20Cord&utm_medium=email&utm_source=Eloqua
3. Cree BAC, Bennett JL, Kim HJ, et al; N-MOmentum study investigators. Inebilizumab for the treatment of neuromyelitis optica spectrum disorder (N-MOmentum): a double-blind, randomised placebo-controlled phase 2/3 trial. Lancet. 2019 Oct 12;394(10206):1352-1363. doi: 10.1016/S0140-6736(19)31817-3. Epub 2019 Sep 5.
4. Trebst C, Jarius S, Berthele A, et al. Update on the diagnosis and treatment of neuromyelitis optica: recommendations of the Neuromyelitis Optica Study Group (NEMOS). J Neurol 2014; 261:1
5. Uplizna (inebilizumab-cdon). IPD Analytics. New Drug Review. June 2020.
6. ClinicalTrials.gov. A Double-masked, Placebo-controlled Study With Open Label Period to Evaluate MEDI-551 in Neuromyelitis Optica and Neuromyelitis Optica Spectrum Disorders. NCT02200770. Available at: https://clinicaltrials.gov/ct2/show/NCT02200770
* CPT only copyright 2020 American Medical Association. All rights reserved. CPT is a registered trademark of the American Medical Association.
(The list of codes is not intended to be all-inclusive and is included below for informational purposes only. Inclusion or exclusion of a procedure, diagnosis, drug or device code(s) does not constitute or imply authorization, certification, approval, offer of coverage or guarantee of payment.)
Medical policies can be highly technical and are designed for use by the Horizon BCBSNJ professional staff in making coverage determinations. Members referring to this policy should discuss it with their treating physician, and should refer to their specific benefit plan for the terms, conditions, limitations and exclusions of their coverage.
The Horizon BCBSNJ Medical Policy Manual is proprietary. It is to be used only as authorized by Horizon BCBSNJ and its affiliates. The contents of this Medical Policy are not to be copied, reproduced or circulated to other parties without the express written consent of Horizon BCBSNJ. The contents of this Medical Policy may be updated or changed without notice, unless otherwise required by law and/or regulation. However, benefit determinations are made in the context of medical policies existing at the time of the decision and are not subject to later revision as the result of a change in medical policy