Efgartigimod Alfa-fcab (Vyvgart) Form

• Efgartigimod alfa-fcab (Vyvgart®) is a neonatal Fc receptor (FcRn) antagonist. • Efgartigimod alfa/hyaluronidase-qvfc (Vyvgart® Hytrulo) is a combination of efgartigimod alfa, a neonatal Fc receptor blocker, and hyaluronidase, an endoglycosidase.
FDA Approved Indication(s)
Vyvgart and Vyvgart Hytrulo are indicated for the treatment of generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) antibody positive. Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria.
It is the policy of health plans affiliated with Centene Corporation® that Vyvgart and Vyvgart Hytrulo are medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Generalized Myasthenia Gravis (must meet all):

1. Diagnosis of gMG;
   2. Prescribed by or in consultation with a neurologist;
   3. Age ≥ 18 years;
   4. Myasthenia Gravis-Activities of Daily Living (MG-ADL) score ≥ 5 at baseline;
   5. Greater than 50% of the baseline MG-ADL score is due to non-ocular symptoms;
   6. Myasthenia Gravis Foundation of America (MGFA) clinical classification of Class II to IV;
2. Member has positive serologic test for anti-AChR antibodies;
   8. Failure of a cholinesterase inhibitor (see Appendix B), unless contraindicated or clinically significant adverse effects are experienced;
3. Failure of a corticosteroid (see Appendix B), unless contraindicated or clinically significant adverse effects are experienced;
4. Failure of at least one immunosuppressive therapy (see Appendix B), unless clinically significant adverse effects are experienced or all are contraindicated;

5. The requested agent is not prescribed concurrently with Soliris® or Ultomiris®;

   12. For Vyvgart requests: Documentation of member’s current weight (in kg); Page 1 of 7

   CLINICAL POLICY Efgartigimod Alfa-fcab, Efgartigimod/Hyaluronidase-qvfc

6. Request meets one of the following (a or b):
   a. Vyvgart: Dose does not exceed 10 mg/kg (1,200 mg per infusion for members weighing 120 kg or more) IV once weekly for the first 4 weeks of every 8-week cycle; b. Vyvgart Hytrulo: Dose does not exceed 1,008 mg/11,200 units SC once weekly for the first 4 weeks of every 8-week cycle.
   Approval duration: 6 months B. Other diagnoses/indications (must meet 1 or 2):
7. 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
8. 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. 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);
9. Member is responding positively to therapy as evidenced by a 2-point reduction in MG-ADL total score;

10. The requested agent is not prescribed concurrently with Soliris or Ultomiris;

    4. For Vyvgart requests: Documentation of member’s current weight (in kg);
    5. If request is for a dose increase, request meets one of the following (a or b):
       a. Vyvgart: New dose does not exceed 10 mg/kg (1,200 mg per infusion for members weighing 120 kg or more) IV once weekly for the first 4 weeks of every 8-week cycle;
       b. Vyvgart Hytrulo: New dose does not exceed 1,008 mg/11,200 units SC once weekly for the first 4 weeks of every 8-week cycle. Approval duration: 6 months
       Page 2 of 7

    CLINICAL POLICY Efgartigimod Alfa-fcab, Efgartigimod/Hyaluronidase-qvfc B. Other diagnoses/indications (must meet 1 or 2):

11. 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

12. 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 FcRn: neonatal Fc receptor FDA: Food and Drug Administration gMG: generalized myasthenia gravis IgG: immunoglobulin G MG-ADL: Myasthenia Gravis-Activities of Daily Living MGFA: Myasthenia Gravis Foundation of America 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 Corticosteroids betamethasone dexamethasone methylprednisolone prednisone Oral: 0.6 to 7.2 mg PO per day Oral: 0.75 to 9 mg/day PO
    Oral: 12 to 20 mg PO per day; increase as needed by 4 mg every 2-3 days until there is marked clinical improvement Oral: 15 mg/day to 20 mg/day; increase by 5 mg every 2-3 days as needed 7.2 mg/day 9 mg/day 40 mg/day 60 mg/day Page 3 of 7

    CLINICAL POLICY Efgartigimod Alfa-fcab, Efgartigimod/Hyaluronidase-qvfc Drug Name Dosing Regimen Cholinesterase Inhibitors pyridostigmine (Mestinon) Oral immediate-release: 600 mg daily in divided doses (range, 60-1,500 mg daily in divided doses) Oral sustained release: 180-540 mg QD or BID Dose Limit/ Maximum Dose Immediate- release: 1,500 mg/day Sustained- release:1,080 mg/day Oral: 375 mg/day 3 mg/kg/day 2 g/day 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) IM or SC: 0.5 mg based on response to therapy neostigmine (Bloxiverz) Immunosuppressants azathioprine (Imuran) mycophenolate mofetil (Cellcept) Oral: 50 mg QD for 1 week, then increase gradually to 2 to 3 mg/kg/day
    Oral: Dosage not established. 1 gram BID has been used with adjunctive corticosteroids or other non-steroidal immunosuppressive medications Oral: initial dose of cyclosporine (non- modified), 5 mg/kg/day in 2 divided doses 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
    5 mg/kg/day cyclosporine (Sandimmune) Rituxan (rituximab), Riabni™ (rituximab- arrx), Ruxience™ (rituximab-pvvr), Truxima (rituximab- abbs)† 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; †Prior authorization is required for rituximab products 375 mg/m2 Appendix C: Contraindications/Boxed Warnings
    None reported Appendix D: General Information • 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. In the Phase 3 ADAPT trial, all study patients received an initial 4-week treatment cycle of Vyvgart, with subsequent cycles administered according to individual clinical response when MG-ADL score was ≥ 5 (i.e., symptoms are at least the minimum threshold • Page 4 of 7

    CLINICAL POLICY Efgartigimod Alfa-fcab, Efgartigimod/Hyaluronidase-qvfc required for necessitating treatment) and, if the patient was an MG-ADL responder to the 4-week treatment cycle, when they no longer had a clinically meaningful decrease (MG- ADL clinically meaningful improvement defined as having ≥ 2-point improvement in total MG-ADL score) compared with baseline. Subsequent cycles could commence no sooner than 8 weeks from initiation of the previous cycle. V. Dosage and Administration Drug Name Efgartigimod alfa- fcab (Vyvgart) Efgartigimod alfa/ hyaluronidase-qvfc (Vyvgart Hytrulo) Dosing Regimen 10 mg/kg IV once weekly for the first 4 weeks of every 8-week cycle 1,008 mg efgartigimod alfa and 11,200 units hyaluronidase administered SC once weekly injections for the first 4 weeks of every 8- week cycle Maximum Dose 10 mg/kg/week (1,200 mg per infusion for members weighing ≥ 120 kg) 1,008 mg/11,200 units per week VI. Product Availability Drug Name Efgartigimod alfa-fcab (Vyvgart) Efgartigimod alfa- hyaluronidase-qvfc (Vyvgart Hytrulo) Availability Single-dose vial: 400 mg/20 mL injection solution Single-dose vial: 1,008 mg (efgartigimod alfa)/11,200 units (hyaluronidase)/5.6 mL VII.