Vutrisiran (ALN-TTRsc02) Form

Vutrisiran (Amvuttra™) is a transthyretin-directed small interfering ribonucleic acid (RNA). FDA Approved Indication(s)
Amvuttra is indicated for the treatment of the polyneuropathy of hereditary transthyretin- mediated (hATTR) amyloidosis in adults. 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 Amvuttra is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Hereditary Transthyretin-Mediated Amyloidosis (must meet all):

1. Diagnosis of hATTR with polyneuropathy;
   2. Prescribed by or in consultation with a neurologist;
   3. Age ≥ 18 years;
   4. Documentation confirms presence of a transthyretin (TTR) mutation;
   5. Biopsy is positive for amyloid deposits or medical justification is provided as to why treatment should be initiated despite a negative biopsy or no biopsy;
2. Member has not had a prior liver transplant;
   
   7. Member has not received prior treatment with Onpattro® or Tegsedi™;
   8. Amvuttra is not prescribed concurrently with Onpattro or Tegsedi;
   9. Dose does not exceed 25 mg every 3 months. Approval duration:
      Medicaid/HIM – 6 months Commercial – 6 months or to the member’s renewal date, whichever is longer B. Other diagnoses/indications (must meet 1 or 2):

3. 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: Page 1 of 6

   CLINICAL POLICY Vutrisiran 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

4. 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. Hereditary Transthyretin-Mediated Amyloidosis (must meet all):
5. 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);
6. Member is responding positively to therapy as evidenced by, including but not limited to, improvement in any of the following parameters: measures of polyneuropathy (e.g., motor strength, sensation, and reflexes), quality of life, motor function, walking ability (e.g., as measured by timed 10-m walk test), and nutritional status (e.g., as evaluated by modified mass index);
7. Member has not had a prior liver transplant;
   
   4. Amvuttra is not prescribed concurrently with Onpattro or Tegsedi;
   5. If request is for a dose increase, new dose does not exceed 25 mg every 3 months. Approval duration:
      Medicaid/HIM – 12 months Commercial – 6 months or to the member’s renewal date, whichever is longer 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 Page 2 of 6

   CLINICAL POLICY Vutrisiran 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 FDA: Food and Drug Administration hATTR: hereditary transthyretin- mediated Appendix B: Therapeutic Alternatives
   Not applicable Appendix C: Contraindications/Boxed Warnings
   None reported RNA: ribonucleic acid TTR: transthyretin Appendix D: General Information • To confirm amyloidosis, the demonstration of amyloid deposits via tissue biopsy is essential. Deposition of amyloid in the tissue can be demonstrated by Congo red staining of biopsy specimens. With Congo red staining, amyloid deposits show a characteristic green birefringence under polarized light; however, negative biopsy results should not be interpreted as excluding the disease.
   • DNA sequencing is usually required for genetic confirmation. Current techniques for performing sequence analysis of TTR, the only gene known to be associated with TTR amyloidosis, detect > 99% of disease-causing mutations. V. Dosage and Administration
   Indication Polyneuropathy of hATTR
   Dosing Regimen 25 mg SC every three months Maximum Dose 25 mg/3 months VI. Product Availability
   Single-dose prefilled syringe: 25 mg/0.5 mL
   VII.