TEGSEDI, Inotersen Sodium Form

Inotersen (Tegsedi™) is a transthyretin-directed antisense oligonucleotide. FDA Approved Indication(s) Tegsedi is indicated for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR) 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 Tegsedi 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. Documentation confirms presence of a transthyretin (TTR) mutation;
   3. 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. Prescribed by or in consultation with a neurologist;
   5. Age ≥ 18 years;
   6. Member has not had a prior liver transplant;
   7. Recent (dated within the last month) platelet count ≥ 100 x 109/L;
   8. Member has not received prior treatment with Amvuttra™ or Onpattro®;
   9. Tegsedi is not prescribed concurrently with Amvuttra or Onpattro;
   10. Dose does not exceed 284 mg (1 syringe) per week. 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 Inotersen 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. Recent (dated within the last month) platelet count ≥ 100 x 109/L;
   3. Member is responding positively to therapy – including but not limited to improvement in any of the following parameters: a. Neuropathy (motor function, sensation, reflexes, walking ability);
      b. Nutrition (body mass index);
      c. Cardiac parameters (Holter monitoring, echocardiography, electrocardiogram, plasma BNP or NT-proBNP, serum troponin); d. Renal parameters (creatinine clearance, urine albumin); e. Ophthalmic parameters (eye exam);
   4. Member has not had a prior liver transplant;
   5. Tegsedi is not prescribed concurrently with Amvuttra or Onpattro;
   6. If request is for a dose increase, new dose does not exceed 284 mg (1 syringe) per week. 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):

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 Page 2 of 6

   CLINICAL POLICY Inotersen 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. 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 BNP: B-type natriuretic peptide
   FDA: Food and Drug Administration hATTR: hereditary transthyretin- mediated amyloidosis
   Appendix B: Therapeutic Alternatives
   Not applicable NT-proBNP: N-terminal pro-B-type natriuretic peptide
   TTR: transthyretin Appendix C: Contraindications/Boxed Warnings • Contraindication(s):
   o Platelet count below 100 x 109/L o History of acute glomerulonephritis caused by Tegsedi o History of a hypersensitivity reaction to Tegsedi • Boxed warning(s): thrombocytopenia and glomerulonephritis • Tegsedi is available only through a restricted distribution program called the Tegsedi REMS Program. V. Dosage and Administration
   Indication hATTR with polyneuropathy Dosing Regimen 284 mg SC once weekly
   Maximum Dose 284 mg/week VI. Product Availability
   Single-dose, prefilled syringe: 284 mg VII.