VYNDAQEL, Tafamidis Meglumine (Cardiac) VYNDAMAX, Form

Tafamidis meglumine (Vyndaqel®) and tafamidis (Vyndamax™) are transthyretin stabilizers. FDA Approved Indication(s) Vyndaqel and Vyndamax are indicated for the treatment of the cardiomyopathy of wild type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) in adults to reduce cardiovascular mortality and cardiovascular-related hospitalization. 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 Vyndaqel and Vyndamax are medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Transthyretin Amyloid Cardiomyopathy (must meet all):

1. Diagnosis of ATTR-CM;

   2. Prescribed by or in consultation with a cardiologist;
   3. Age ≥ 18 years;
   4. Diagnosis is supported by one of the following (a or b): a. Tissue biopsy amyloid protein is identified as transthyretin via mass spectrometry or immunohistochemistry, and (i or ii):
      i. Tissue biopsy is of endomyocardial origin; ii. Tissue biopsy is of extra-cardiac origin and echocardiography (Echo), cardiac magnetic resonance imaging (CMR), or positron emission tomography (PET) findings are consistent with cardiac amyloidosis; b. Member meets all of the following (i, ii, and iii): i. Echo, CMR, or PET findings are consistent with cardiac amyloidosis; ii. Cardiac uptake is Grade 2 or 3 on a radionuclide scan utilizing one of the following radiotracers (a, b, or c): a) 99m technetium (Tc)-labeled 3,3-diphosphono-1,2-propanodicarboxylic acid (DPD); b) 99mTc-labeled pyrophosphate (PYP); c) 99mTc-labeled hydroxymethylene diphosphonate (HMDP); iii. Each of the following laboratory tests is negative for monoclonal protein (a, b, and c): Page 1 of 6

   CLINICAL POLICY Tafamidis a) Serum kappa/lambda free light chain ratio analysis; b) Serum protein immunofixation; c) Urine protein immunofixation;

2. Member has not had a liver transplant;
   6. Vyndaqel/Vyndamax is not prescribed concurrently with Onpattro® and Tegsedi®;
   7. Dose does not exceed either of the following (a or b): a. Vyndaqel: 80 mg (4 capsules) per day; b. Vyndamax: 61 mg (1 capsule) per day. Approval duration: 6 months 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: 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. Transthyretin Amyloid Cardiomyopathy (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, including but not limited to improvement or stabilization in any of the following parameters: a. Walking ability; b. Nutrition (e.g., body mass index);
   c. Cardiac related hospitalization; d. Cardiac procedures or laboratory tests (e.g., Holter monitoring, echocardiography, electrocardiogram, plasma BNP or NT-proBNP, serum troponin);

7. Vyndaqel/Vyndamax is not prescribed concurrently with Onpattro® and Tegsedi®;

   4. Dose does not exceed either of the following (a or b): a. Vyndaqel: 80 mg (4 capsules) per day; Page 2 of 6

   CLINICAL POLICY Tafamidis b. Vyndamax: 61 mg (1 capsule) per day. Approval duration: 12 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 ATTR-CM: cardiomyopathy of transthyretin-mediated amyloidosis FDA: Food and Drug Administration Appendix B: Therapeutic Alternatives
   Not applicable Appendix C: Contraindications/Boxed Warnings None reported Appendix D: General Information • There is no evidence supporting the safety and efficacy of concurrent use of Onpattro or Tegsedi with Vyndaqel/Vyndamax. The pivotal trials for Onpattro and Tegsedi did not allow concurrent use of tetramer stabilizers (e.g., tafamidis, diflunisal). In the APOLLO Phase II open-label extension in 27 patients treated with Onpattro (13 treated concomitantly with Onpattro and tafamidis), transthyretin reduction was similar over 24 months, regardless of concomitant transthyretin stabilizers (i.e., tafamadis, diflunisal). Page 3 of 6

   CLINICAL POLICY Tafamidis V. Dosage and Administration
   Drug Name Tafamidis (Vyndaqel) Tafamidis (Vyndamax) Dosing Regimen 80 mg (4 capsules) PO QD 61 mg (1 capsule) PO QD
   Maximum Dose 80 mg/day 61 mg/day VI. Product Availability
   Drug Name Tafamidis meglumine (Vyndaqel) Tafamidis (Vyndamax) Availability
   Capsules: 20 mg Capsules: 61 mg VII.