Last Review Date: 2/01/2024

Date of Origin: 08/08/2023

Dates Reviewed: 08/2023, 12/2023, 2/2024

1. Length of Authorization ¹

Initial coverage will be provided for 16 weeks. Coverage may be renewed every 6 months thereafter.

2. Dosing Limits

A. Quantity Limit (max daily dose) [NDC Unit]:

• Rystiggo 280 mg/2 mL single-dose vial: 3 vials per week for 6 doses per 63 days

B. Max Units (per dose and over time) [HCPCS Unit]:

• 840 billable units (840 mg) weekly for 6 doses per 63 days

3. Initial Approval Criteria ¹

Coverage is provided in the following conditions:

• Patient is at least 18 years of age; AND

Universal Criteria ^1,3

• Will not be used in combination with other immunomodulatory biologic therapies (e.g., rituximab, eculizumab, ravulizumab, pegcetacoplan, satralizumab, inebilizumab, efgartigimod, zilucoplan, etc.); AND
• Patient will avoid or use with caution medications known to worsen or exacerbate symptoms of myasthenia gravis (MG) (e.g., certain antibiotics, beta-blockers, botulinum toxins, hydroxychloroquine, etc.); AND
• Will not be administered with live-attenuated or live vaccines during treatment; AND
• Patient does not have an active infection, including clinically important localized infections; AND
• Patient does not have a deficiency of immunoglobulin G (IgG) necessitating supplementation with IgG; AND

Generalized Myasthenia Gravis (gMG) † Ф ^1,3-6,8

• Patient has Myasthenia Gravis Foundation of America (MGFA) Clinical Classification of Class II to IV disease §; AND
• Patient has a positive serologic test for anti-acetylcholine receptor (AChR) or anti-muscle-specific tyrosine kinase (MuSK) antibodies; AND
• Patient has had a thymectomy (Note: Applicable only to patients with AChR positive disease and with thymomas OR non-thymomatous patients who are 50 years of age or younger); AND
• Physician has assessed objective signs of neurological weakness and fatiguability on a baseline neurological examination (e.g., including, but not limited to, the Quantitative Myasthenia Gravis (QMG) score, etc.); AND
• Patient has a baseline MG-Activities of Daily Living (MG-ADL) total score of at least 3; AND
  • Patient had an inadequate response to initial therapy based on their antibodies:
    • AChR+ disease:

• • • • A minimum one-year trial of concurrent use with two (2) or more immunosuppressive therapies (e.g., corticosteroids plus an immunosuppressant such as azathioprine, cyclosporine, mycophenolate, etc.); OR
• MuSK+ disease: a minimum one-year trial with immunosuppressive therapy (e.g., corticosteroids, azathioprine, or mycophenolate) and rituximab; OR
• Patient required at least one acute or chronic treatment with plasmapheresis or plasma exchange (PE) or intravenous immunoglobulin (IVIG) in addition to immunosuppressant therapy

† FDA Approved Indication(s); ‡ Compendia Recommended Indication(s); Ф Orphan Drug

4. Renewal Criteria ¹

Coverage can be renewed based upon the following criteria:

• Patient continues to meet universal and other indication-specific relevant criteria identified in section III; AND
• Absence of unacceptable toxicity from the drug. Examples of unacceptable toxicity include: infection, severe hypersensitivity reactions (e.g., rash, angioedema, etc.), aseptic meningitis, etc.; AND
• Patient has had an improvement (i.e., reduction) of at least 1-point from baseline in the Myasthenia Gravis-Specific Activities of Daily Living scale (MG-ADL) total score Δ; AND
• Improvement in muscle strength testing with fatigue maneuvers as evidenced on neurologic examination when compared to baseline; AND
• Patient requires continuous treatment, after an initial beneficial response, due to new or worsening disease activity (Note: a minimum of 63 days must have elapsed from the start of the previous treatment cycle)

(Δ May substitute an improvement of at least 1-point from baseline in the Quantitative Myasthenia Gravis (QMG) total score, if available)

5. Dosage/Administration ¹

6. Billing Code/Availability Information

HCPCS Code:

• J9333 – Injection, rozanolixizumab-noli, 1 mg; 1 billable unit = 1 mg

NDC:

• Rystiggo 280mg/2mL solution in a single-dose vial: 50474-0980-xx

7. References

1. Rystiggo [package insert]. Smyrna, GA; UCB, Inc., June 2023. Accessed January 2024.
2. Sussman J, Farrugia ME, Maddison P, et al. Myasthenia gravis: Association of British Neurologists’ management guidelines. Pract Neurol 2015; 15: 199-206.
3. Narayanaswami P, Sanders D, Wolfe G, Benatar M, et al. International consensus guidance for management of myasthenia gravis, 2020 update. Neurology® 2021;96:114-122. doi:10.1212/WNL.0000000000011124.
4. Bril V, Drużdż A, Grosskreutz J, and MG0003 study team. Safety and efficacy of rozanolixizumab in patients with generalised myasthenia gravis (MycarinG): a randomised, double-blind, placebo-controlled, adaptive phase 3 study. Lancet Neurol. 2023 May;22(5):383-394. doi: 10.1016/S1474-4422(23)00077-7. PMID: 37059507. https://pubmed.ncbi.nlm.nih.gov/37059507
5. Jayam-Trouth A, Dabi A, Solieman N, Kurukumbi M, Kalyanam J. Myasthenia gravis: a review. Autoimmune Dis. 2012;2012:874680. doi:10.1155/2012/874680
6. Bril V, Druzdz A, Grosskreutz J, et al. Long-term Efficacy and Safety of Symptom-driven Cyclic Rozanolixizumab Treatment in Patients with Generalized Myasthenia Gravis: A Pooled Analysis of a Phase 3 Study and Two Open-label Extension Studies (P1-5.012). Neurology Apr 2023, 100 (17 Supplement 2) 3747; DOI: 10.1212/WNL.0000000000203497
7. Guidon AC, Muppidi S, Nowak RJ,  et al. Telemedicine visits in myasthenia gravis: expert guidance and the Myasthenia Gravis Core Exam (MG-CE). Muscle Nerve 2021; 64:270-276
8. Gronseth GS, Barohn R, Narayanaswami P. Practice advisory: Thymectomy for myasthenia gravis (practice parameter update): Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology. 2020;94(16):705. Epub 2020 Mar 25.
9. Bril V, Benatar M, Andersen H, MG0002 Investigator Study Group, et al. Efficacy and Safety of Rozanolixizumab in Moderate to Severe Generalized Myasthenia Gravis A Phase 2 Randomized Control Trial. Neurology Feb 2021, 96 (6) e853-e865; DOI: 10.1212/WNL.0000000000011108.

Appendix 1 – Covered Diagnosis Codes

Appendix 2 – Centers for Medicare and Medicaid Services (CMS)

The preceding information is intended for non-Medicare coverage determinations. Medicare coverage for outpatient (Part B) drugs is outlined in the Medicare Benefit Policy Manual (Pub. 100-2), Chapter 15, §50 Drugs and Biologicals. In addition, National Coverage Determinations (NCDs) and/or Local Coverage Determinations (LCDs) may exist and compliance with these policies is required where applicable. Local Coverage Articles (LCAs) may also exist for claims payment purposes or to clarify benefit eligibility under Part B for drugs which may be self-administered. The following link may be used to search for NCD, LCD, or LCA documents: https://www.cms.gov/medicare-coverage-database/search.aspx. Additional indications, including any preceding information, may be applied at the discretion of the health plan.

Medicare Part B Covered Diagnosis Codes (applicable to existing NCD/LCD/LCA): N/A