Last Review Date: 07/02/2024

Date of Origin: 07/05/2023

Dates Reviewed: 07/2023, 09/2023, 12/2023, 2/2024, 07/2024

1. Length of Authorization ¹

• CIDP: Initial coverage will be provided for 6 months and may be renewed annually thereafter.
• gMG: Initial coverage will be provided for 90 days. Coverage may be renewed every 6 months thereafter.

2. Dosing Limits

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

• Vyvgart Hytrulo 1,008 mg/11,200 units (efgartigimod alfa/hyaluronidase) single-dose vial: 1 vial per week

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

• CIDP: 504 billable units weekly
• gMG: 504 billable units weekly for four doses per 50 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

• 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

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) ^1,9,10

• Patient’s disease course is progressive or relapsing and remitting for >2 months; AND
• Patient has decreased or absent deep tendon reflexes in upper or lower limbs; AND
• Electrodiagnostic testing indicating demyelination:

• Partial motor conduction block in at least 2 motor nerves or in 1 nerve plus one other demyelination criterion listed here in at least 1 other nerve; OR
• Distal CMAP duration increase in at least 1 nerve plus one other demyelination criterion listed here in at least 1 other nerve; OR
• Abnormal temporal dispersion conduction must be present in at least 2 motor nerves; OR
• Reduced motor conduction velocity in at least 2 motor nerves; OR
• Prolonged distal motor latency in at least 2 motor nerves; OR
• Absent F wave in at least 2 motor nerves plus one other demyelination criterion listed here in at least 1 other nerve; OR
• Prolonged F wave latency in at least 2 motor nerves; AND

• Baseline CIDP Disease Activity Status (CDAS) score ≥2; AND

• Baseline in strength/weakness has been documented using an objective clinical measuring tool (e.g., INCAT, Medical Research Council (MRC) muscle strength, 6-MWT, Rankin, Modified Rankin, etc.; AND
• Patient has tried and failed on at least 3-month trial of immunoglobulin (IG) or plasma exchange therapy; AND
• Will not be used as maintenance therapy in combination with immunoglobulin or intravenous efgartigimod

Generalized Myasthenia Gravis (gMG) † Ф ^1,3-5,8

• 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) antibodies; AND
• Patient has had a thymectomy (Note: Applicable only to patients 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 5; AND
  • Patient had an inadequate response after 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
  • Patient required at least one acute or chronic treatment with plasmapheresis or plasma exchange (PE) or intravenous immunoglobulin (IVIG) in addition to immunosuppressant therapy; 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 used in combination with other immunomodulatory biologic therapies (i.e., rituximab, eculizumab, ravulizumab, pegcetacoplan, satralizumab, inebilizumab, rozanolixizumab, zilucoplan, etc.) or with intravenous efgartigimod

† 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 the 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., anaphylaxis, rash, angioedema, and dyspnea, etc.), severe infusion-related reactions, etc.; AND

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) ^1,9,10

• Patient has demonstrated a clinical response to therapy based on an objective clinical measuring tool (e.g., INCAT, Medical Research Council (MRC) muscle strength, 6-MWT, Rankin, Modified Rankin, etc.)

Generalized Myasthenia Gravis (gMG) ¹

• 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 50 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

   Indication	Dose
   Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)	Administer 1,008 mg / 11,200 units (1,008 mg efgartigimod alfa and 11,200 units hyaluronidase) subcutaneously over approximately 30 to 90 seconds once weekly.
   Generalized Myasthenia Gravis (gMG)	Administer 1,008 mg / 11,200 units (1,008 mg efgartigimod alfa and 11,200 units hyaluronidase) subcutaneously over approximately 30 to 90 seconds in cycles of once weekly injections for 4 weeks. Administer subsequent treatment cycles based on clinical evaluation. The safety of initiating subsequent cycles sooner than 50 days from the start of the previous treatment cycle has not been established.
   Note: Vyvgart Hytrulo is to be administered by a healthcare professional only.

6. Billing Code/Availability Information

HCPCS Code:

• J9334 – Injection, efgartigimod alfa, 2 mg and hyaluronidase-qvfc; 1 billable unit = 2 mg

NDC:

• Vyvgart Hytrulo 1,008 mg efgartigimod alfa and 11,200 units hyaluronidase per 5.6 mL (180 mg/2,000 units per mL) single-dose vial: 73475-3102-xx

7. References

1. Vyvgart Hytrulo [package insert]. Boston, MA; Argenx US, Inc., June 2024. Accessed June 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. Howard JF Jr, Bril V, Vu T, Karam C, ADAPT Investigator Study Group, et al. Safety, efficacy, and tolerability of efgartigimod in patients with generalised myasthenia gravis (ADAPT): a multicentre, randomised, placebo-controlled, phase 3 trial. Lancet Neurol. 2021 Jul;20(7):526-536. doi: 10.1016/S1474-4422(21)00159-9. Erratum in: Lancet Neurol. 2021 Aug;20(8):e5.
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. Institute for Clinical and Economic Review. Eculizumab and Efgartigimod for the Treatment of Myasthenia Gravis: Effectiveness and Value. Draft evidence report. July 22, 2021. https://icer.org/wp-content/uploads/2021/03/ICER_Myasthenia-Gravis_Draft-Evidence-Report_072221.pdf. Accessed January 12, 2024.
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. Van den Bergh PY, Hadden RD, Bouche P, et al. European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy: report of a joint task force of the European Federation of Neurological Societies [trunc]. Eur J Neurol 2010 Mar;17(3):356-63.
10. Van den Bergh PYK, van Doorn PA, Hadden RDM, et al. European Academy of Neurology/Peripheral Nerve Society guideline on diagnosis and treatment of chronic inflammatory demyelinating polyradiculoneuropathy: Report of a joint Task Force-Second revision. J Peripher Nerv Syst. 2021 Sep;26(3):242-268. doi: 10.1111/jns.12455. Erratum in: J Peripher Nerv Syst. 2022 Mar;27(1):94. Erratum in: Eur J Neurol. 2022 Apr;29(4):1288.
11. Allen J, Basta I, Eggers C, et al. Efficacy, Safety, and Tolerability of Efgartigimod in Patients with Chronic Inflammatory Demyelinating Polyneuropathy: Results from the ADHERE Trial (PL5.002). Neurology. April 9, 2024 issue; 102 (17_supplement_1). https://doi.org/10.1212/WNL-.0000000000206324.

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