ONPATTRO, Patisiran Sodium Form

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

1. Diagnosis of hereditary TTR-mediated amyloidosis with polyneuropathy;
   2. Documentation confirms presence of a 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. Member has not received prior treatment with Amvuttra™ or Tegsedi™;
   8. Onpattro is not prescribed concurrently with Amvuttra or Tegsedi;
   9. Dose does not exceed the following (based on actual body weight): a. Weight < 100 kg: 0.3 mg/kg once every 3 weeks; b. Weight ≥ 100 kg: 30 mg once every 3 weeks.
      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): Page 1 of 6

   CLINICAL POLICY Patisiran 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

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 [e.g., improved measures of polyneuropathy (e.g., motor strength, sensation, and reflexes), improvement in 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. Onpattro is not prescribed concurrently with Amvuttra or Tegsedi;
   5. If request is for a dose increase, new dose does not exceed the following (based on actual body weight):
      a. Weight < 100 kg: 0.3 mg/kg once every 3 weeks; b. Weight ≥ 100 kg: 30 mg once every 3 weeks. 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: Page 2 of 6

   CLINICAL POLICY Patisiran 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 or CP.PMN.53 for Medicaid and HIM-Medical Benefit, or evidence of coverage documents.
   IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key FDA: Food and Drug Administration TTR: transthyretin Appendix B: Therapeutic Alternatives
   Not applicable
   Appendix C: Contraindications/Boxed Warnings None reported 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 Hereditary TTR- mediated amyloidosis- associated polyneuropathy Dosing Regimen • Adults weighing < 100 kg: 0.3 mg/kg IV every 3 weeks • Adults weighing ≥ 100 kg: 30 mg IV every 3 Maximum Dose See dosing regimen weeks • Premedicate with a corticosteroid, acetaminophen, and antihistamines to reduce the risk of infusion-related reactions.
   • Onpattro should be administered by a healthcare professional. Page 3 of 6

   CLINICAL POLICY Patisiran VI. Product Availability
   Lipid complex injection (single-dose vial): 10 mg/5 mL (2 mg/mL)
   VII.