Viltolarsen (Viltepso) Form

Viltolarsen (Viltepso®) is an antisense oligonucleotide. FDA Approved Indication(s) Viltepso is indicated for the treatment of Duchenne muscular dystrophy (DMD) in patients who have a confirmed mutation of the DMD gene that is amenable to exon 53 skipping. Limitation(s) of use: This indication is approved under accelerated approval based on an increase in dystrophin production in skeletal muscle observed in patients treated with Viltepso. Continued approval for this indication may be contingent upon verification of a clinical benefit in a confirmatory trial. 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.
All requests reviewed under this policy may require medical director review. It is the policy of health plans affiliated with Centene Corporation® that Viltepso may be medically necessary* when the following criteria are met:

• Viltepso was FDA-approved based on an observed increase in dystrophin in skeletal muscle, but it is unknown if that increase is clinically significant. Continued FDA-approval for this indication may be contingent upon verification of a clinical benefit in confirmatory trials. I. Initial Approval Criteria A. Duchenne Muscular Dystrophy (must meet all):

  1. Diagnosis of DMD with mutation amenable to exon 53 skipping (see Appendix D) confirmed by genetic testing;
  2. Prescribed by or in consultation with a neurologist;
  3. Age ≤ 9 years at therapy initiation;
  4. Member has all of the following assessed within the last 30 days (a, b, and c): a. Ambulatory function (e.g., ability to walk with or without assistive devices, not wheelchair dependent) with one of the following (i or ii): i. 6-minute walk test (6MWT) distance ≥ 201 m; ii. Time-to-stand (TTSTAND) < 10 seconds; b. Stable cardiac function with left ventricular ejection fraction (LVEF) ≥ 40%; Page 1 of 8

  CLINICAL POLICY Viltolarsen c. Stable pulmonary function with predicted forced vital capacity (FVC) ≥ 50%;

  5. Inadequate response (as evidenced by a significant decline in 6MWT, TTSTAND, LVEF, or FVC) despite adherent use of an oral corticosteroid (e.g., prednisone, Emflaza®, Agamree®) for ≥ 6 months, unless contraindicated or clinically significant adverse effects are experienced; *Prior authorization is required for Emflaza and Agamree
  6. Viltepso is prescribed concurrently with an oral corticosteroid, unless contraindicated or clinically significant adverse effects are experienced;
  7. Viltepso is not prescribed concurrently with other exon-skipping therapies (e.g., Amondys 45™, Exondys 51®, Vyondys 53™);
  8. Member has not previously received gene replacement therapy for DMD (e.g., Elevidys);
  9. Dose does not exceed 80 mg/kg per week. Approval duration: 6 months B. Other diagnoses/indications (must meet 1 or 2):
  10. 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
  11. 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. Duchenne Muscular Dystrophy (must meet all):
  12. Currently receiving medication for DMD with mutation amenable to exon 53 skipping or member has previously met initial approval criteria;
  13. Member is responding positively to therapy as evidenced by one of the following (a or b): a. All of the following assessed within the last 6 months (i, ii, and iii): i. Ambulatory function (e.g., ability to walk with or without assistive devices, not wheelchair dependent) with one of the following (1 or 2): 1) 6MWT distance ≥ 201 m; 2) TTSTAND < 10 seconds; ii. Stable cardiac function with LVEF ≥ 40%; iii. Stable pulmonary function with predicted FVC ≥ 50%; Page 2 of 8

  CLINICAL POLICY Viltolarsen b. Member has received this medication via a healthcare insurer without meeting the requirements above (see criterion 2a), and medical record shows improved or stable LVEF and FVC, assessed within the last 6 months;

  3. Member has been assessed by a neurologist within the last 6 months;
  4. Viltepso is prescribed concurrently with an oral corticosteroid, unless contraindicated or clinically significant adverse effects are experienced;
  5. Viltepso is not prescribed concurrently with other exon-skipping therapies (e.g., Amondys 45, Exondys 51, Vyondys 53);
  6. Member has not previously received gene replacement therapy for DMD (e.g., Elevidys);
  7. If request is for a dose increase, new dose does not exceed 80 mg/kg per week. Approval duration: 6 months B. Other diagnoses/indications (must meet 1 or 2):
  8. 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
  9. 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 6MWT: 6-minute walk test DMD: Duchenne muscular dystrophy FDA: Food and Drug Administration FVC: forced vital capacity ICER: Institute for Clinical and Economic Review LVEF: left ventricular ejection fraction TTSTAND: time to stand Page 3 of 8

  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.
  Dosing Regimen Drug Name Dose Limit/ Maximum Dose Based on weight Based on weight See regimen prednisone Emflaza® (deflazacort) Agamree®
  (vamorolone) 0.3-0.75 mg/kg/day or 10 mg/kg/weekend PO 0.9 mg/kg/day PO QD 6 mg/kg/day PO QD (up to a maximum of 300 mg/day)
  • If member has mild (Child-Pugh A) to moderate (Child-Pugh B) hepatic impairment: 2 mg/kg/day PO QD (up to a maximum of 100 mg/day)
  If co-administered with strong CYP3A4 inhibitors (e.g., itraconazole): 4 mg/kg/day PO QD (up to a maximum of 200 mg/day)
  • 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 None reported Appendix D: General Information
  • Common mutations amenable to exon 53 skipping include: 3-52, 4-52, 5-52, 6-52, 9-52, 10-52, 11-52, 13-52, 14-52, 15-52, 16-52, 17-52, 19-52, 21-52, 23-52, 24-52, 25-52, 26- 52, 27-52, 28-52, 29-52, 30-52, 31-52, 32-52, 33-52, 34-52, 35-52, 36-52, 37-52, 38-52, 39-52, 40-52, 41-52, 42-52, 43-52, 45-52, 47-52, 48-52, 49-52, 50-52, 52, 54-58, 54-61, 54-64, 54-66, 54-76, 54-77. • Corticosteroids are routinely used in DMD management with established efficacy in slowing decline of muscle strength and function (including motor, respiratory, and cardiac). They are recommended for all DMD patients per the American Academy of Neurology (AAN) and DMD Care Considerations Working Group; in addition, the AAN guidelines have been endorsed by the American Academy of Pediatrics, the American Association of Neuromuscular & Electrodiagnostic Medicine, and the Child Neurology Society.
  o The DMD Care Considerations Working Group guidelines, which were updated in 2018, continue to recommend corticosteroids as the mainstay of therapy.
  o In an evidence report published August 2019, the Institute for Clinical and Economic Review (ICER) states that current evidence is insufficient to conclude that other exon-skipping therapies (Exondys 51, Vyondys 53) have net clinical benefit when added to corticosteroids and supportive care versus corticosteroids and supportive care alone.
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  CLINICAL POLICY Viltolarsen • Prednisone is the corticosteroid with the most available evidence. A second corticosteroid commonly used is deflazacort, which was FDA approved for DMD in February 2017. On October 2023, a third corticosteroid, vamorolone, was approved by the FDA for DMD. • The phase 2 dose-finding, safety study for viltolarsen (NCT02740972) enrolled male patients age 4-9 years with the lowest 6MWT distance at baseline being 201 m. In addition, inclusion criteria for the ongoing phase 3 efficacy study for viltolarsen (RACER 53; NCT04060199) enrolled male patients age 4-7 years old with a TTSTAND < 10 seconds. • Having an LVEF below 40% may indicate presence of cardiomyopathy or heart failure, while a predicted FVC below 50% may indicate presence of severe pulmonary disease.
  V. Dosage and Administration Indication DMD Dosing Regimen 80 mg/kg IV once weekly Maximum Dose 80 mg/kg/week VI. Product Availability
  Solution for injection in a single-dose vial: 250 mg/5 mL (50 mg/mL) VII.