VYONDYS 53, Golodirsen Form

Golodirsen (Vyondys 53™) is an antisense oligonucleotide. FDA Approved Indication(s) Vyondys 53 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 Vyondys 53. Continued approval for this indication may be contingent upon verification of a clinical benefit in confirmatory trials. 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 Vyondys 53 may be medically necessary* when the following criteria are met:

• Vyondys 53 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. Age ≤ 15 years at therapy initiation;
  3. Prescribed by or in consultation with a neurologist;
  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 a 6-minute walk test (6MWT) distance ≥ 250 m; b. Stable cardiac function with left ventricular ejection fraction (LVEF) ≥ 50%; c. Stable pulmonary function with predicted forced vital capacity (FVC) ≥ 50%; Page 1 of 7

  CLINICAL POLICY Golodirsen

  5. Inadequate response (as evidenced by a significant decline in 6MWT, 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. Vyondys 53 is prescribed concurrently with an oral corticosteroid, unless contraindicated or clinically significant adverse effects are experienced;
  7. Vyondys 53 is not prescribed concurrently with other exon-skipping therapies (e.g., Amondys 45™, Exondys 51®, Viltepso®);
  8. Member has not previously received gene replacement therapy for DMD (e.g., Elevidys);
  9. Dose does not exceed 30 mg/kg per week. Approval duration: 6 months
     II. Continued Therapy A. Duchenne Muscular Dystrophy (must meet all):
  10. Currently receiving medication for DMD with mutation amenable to exon 53 skipping or member has previously met initial approval criteria;
  11. 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 a 6MWT distance ≥ 250 m; ii. Stable cardiac function with LVEF ≥ 50%; iii. Stable pulmonary function with predicted FVC ≥ 50%; 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;
  12. Member has been assessed by a neurologist within the last 6 months;
  13. Vyondys 53 is prescribed concurrently with an oral corticosteroid, unless contraindicated or clinically significant adverse effects are experienced;
  14. Vyondys 53 is not prescribed concurrently with other exon-skipping therapies (e.g., Amondys 45, Exondys 51, Viltepso);
  15. Member has not previously received gene replacement therapy for DMD (e.g., Elevidys);
  16. If request is for a dose increase, new dose does not exceed 30 mg/kg per week.
      Approval duration: 6 months
      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.
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  CLINICAL POLICY Golodirsen 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 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 0.3-0.75 mg/kg/day or 10 mg/kg/weekend PO Based on weight Based on weight 0.9 mg/kg/day PO QD prednisone Emflaza® (deflazacort) Agamree®
  (vamorolone) See regimen 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.
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  CLINICAL POLICY Golodirsen 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 Vyondys 53 has net clinical benefit when added to corticosteroids and supportive care versus corticosteroids and supportive care alone.
  • 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 inclusion criteria for Study 4053-US-101 (NCT02310906) used to support the FDA approval of Vyondys 53 enrolled male patients age 6-15 years old with a mean 6MWT distance of 250 m or more at screening and baseline visits, LVEF ≥ 50% based on screening echocardiogram (ECHO), and stable pulmonary function with FVC ≥ 50%. V. Dosage and Administration
  Indication DMD Dosing Regimen 30 mg/kg IV once weekly Maximum Dose 30 mg/kg/week VI. Product Availability
  Single-dose vial for injection: 100 mg/2 mL (50 mg/mL) VII.