137 Form

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Pharmacy Medical Policy Transthyretin-Mediated Amyloidosis Medications

Table of Contents: Authorization Information Coverage Criteria
Description
Appendix Policy History
Coding Information References

Policy Number: 137

Related Policies • BCBSA Reference Number: N/A • Medical Benefit Prior Authorization Medication List #034 • Quality Care Dosing guidelines may apply to the following medications and can be found in Medical Policy #621

Prior Authorization Information

Policy ☒ Prior Authorization ☐ Step Therapy ☒ Quality Care Dosing ☐ Administrative Reviewing Department Pharmacy Operations: Tel: 1-800-366-7778 Fax: 1-800-583-6289 To request for coverage: Providers may call, fax, or mail the attached form (Formulary Exception/Prior Authorization form) to the address below.
Blue Cross Blue Shield of Massachusetts Pharmacy Operations Department 25 Technology Place Hingham, MA 02043
Tel: 1-800-366-7778 Fax: 1-800-583-6289

Individual Consideration for the atypical patient: Policy for requests that do not meet clinical criteria of this policy, see section labeled Individual Consideration
Policy Last Updated 3/15/2026 Pharmacy (Rx) or Medical (MED) benefit coverage ☒ Rx ☒ MED Policy applies to Commercial members with BCBSMA formulary:
• Managed Care (HMO/POS) • PPO/EPO
• Indemnity
Policy does NOT apply to: • Medicare Advantage
Provider Documentation Requirements: Documentation from the provider to support a reason preventing trial of formulary alternative(s) must include the name and strength of alternatives tried and failed (if alternatives were tried, including dates if available) and specifics regarding the treatment failure. Documentation to support clinical basis preventing switch to formulary alternative should also provide specifics around clinical reason. We may also use prescription claims records to establish prior use of formulary alternatives or to show if step therapy criteria has been met. We will require the provider to share additional information when prescription claims data is either not available or the medication fill history fails to establish use of preferred formulary medications or that step therapy criteria has been met. Other documentation requirements, if any, are outlined in prior authorization criteria.
See Appendix for additional information.

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Please refer to the chart below for the formulary status/requirements of the medications affected by this policy:

Drug Diagnosis Notes Antisense Oligonucleotide Wainua (Eplontersen) • Polyneuropathy of hereditary transthyretin-mediated amyloidosis PA, QCD siRNA Agents Onpattro (Patisiran) • Polyneuropathy of hereditary transthyretin-mediated amyloidosis PA Amvuttra
(Vutrisiran) • Polyneuropathy of hereditary transthyretin-mediated amyloidosis • Cardiomyopathy associated with wild-type or hereditary transthyretin- mediated amyloidosis

Medical, PA Transthyretin Stabilizers Attruby (acoramidis)

Cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis

PA, QCD Different forms of tafamidis result in two options: Vyndaqel (4 caps/day) and Vyndamax (1 cap/day) Vyndamax (Tafamidis) Vyndaqel (Tafamidis) PA – Prior Authorization; NFNC – Non-formulary, Non-Covered; QCD (Quality Care Dosing – refer to Policy 621b), Medical -- This medication is excluded from the pharmacy benefit. It may be covered by the medical benefit. Approval Length: 12 months, unless otherwise specified in Clinical Guideline Coverage Criteria

Clinical Guideline Coverage Criteria: Polyneuropathy of Hereditary Transthyretin- mediated Amyloidosis

Coverage may be considered MEDICALLY NECESSARY when ALL the following criteria are met. Diagnosis Polyneuropathy of Hereditary Transthyretin-mediated Amyloidosis Applicable Medications • Amvuttra (Vutrisiran) • Onpattro (Patisiran) • Wainua (Eplontersen)

1. Confirmed diagnosis of hereditary transthyretin-mediated amyloidosis (hATTR) as confirmed by at least ONE of the following: a. Tissue biopsy showing amyloid deposition b. a gene test confirming hATTR mutation
   AND
2. Age ≥ 18 years AND

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3. Prescribed by all relevant specialties or in consultation with physicians experienced in the treatment of ATTR amyloidosis (e.g. a board certified or board-eligible cardiologist, neurologist). AND

4. Documented severity of polyneuropathy as characterized by at least ONE of the following: a. Has a baseline Polyneuropathy Disability (PND) IIIb or lower b. Baseline Familial Amyloid Polyneuopathy (FAP): stage one or two

   Clinical Guideline Coverage Criteria: Cardiomyopathy of Wild-type or Hereditary Transthyretin-mediated Amyloidosis

   Coverage may be considered MEDICALLY NECESSARY when ALL the following criteria are met. Diagnosis Cardiomyopathy Associated with Wild-type or Hereditary Transthyretin-mediated Amyloidosis Applicable Medications • Amvuttra (Vutrisiran) • Attruby (acoramidis) • Vyndamax (Tafamidis) • Vyndaqel (Tafamidis)

5. Confirmed diagnosis of cardiomyopathy associated with hereditary transthyretin-mediated amyloidosis (hATTR) OR wild-type transthyretin-mediated amyloidosis (wtATTR), confirmed by at least ONE of the following: a. Bone scintigraphy
   b. Endomyocardial biopsy
   c. Echocardiography
   d. Cardiovascular Magnetic Resonance AND
6. Age ≥ 18 years AND

7. Prescribed by all relevant specialties or in consultation with physicians experienced in the treatment of ATTR amyloidosis (e.g. a board certified or board-eligible cardiologist, neurologist).

   Description

   Amyloidosis is a general term used to describe when highly ordered fibrils, made of a variety of low molecular weight subunits of proteins, are deposited to extracellular tissue. These amyloid deposits can result in clinical manifestations that range based on amount, type, and location. There are 28 known localized forms of amyloidosis and 18 different types of systemic amyloidosis. ATTR amyloid is one major form of amyloidosis and can manifest because with (hATTR, hereditary) or without (wtATTR, wild-type). genetic mutations. These can be associated with cardiomyopathy and/or neuropathy.

   wtATTR amyloidosis (wild type) – Formerly known as senile systemic amyloidosis, wild-type transthyretin amyloidosis is caused by deposits of misfolded transthyretin. What causes these pathogenic deposits is currently not clear.

   hATTR amyloidosis (hereditary) – Mutation in the transthyretin gene (TTR) is the cause of hereditary transthyretin amyloidosis. This mutation predisposes the transthyretin structure to become unstable,

4 resulting in misfolding and tissue deposition. Genetic transmission is autosomal dominant inheritance with variable penetrance.

Polyneuropathy due to hereditary transthyretin-mediated amyloidosis due can be treated with specific disease-modifying treatments such as transthyretin gene silencers including patisiran, vutrisiran, inotersen, and eplontersen.

Cardiomyopathy associated with wild-type or hereditary transthyretin-mediated amyloidosis can be treated with tafamidis, acoramidis, or vutrisiran. There is insufficient evidence to support combination therapy.

Appendix

Formulary Status All requests must meet the Prior Authorization requirement. For non-covered medications, the member must also have had a previous treatment failure with, or contraindication to, at least two covered formulary alternatives when available. See section on individual consideration for more information if you require an exception to any of these criteria requirements for an atypical patient.
Member cost share consideration For those drugs that may be covered under the pharmacy benefit, a higher non-preferred cost share may be applied if an exception request is approved for coverage of a non- preferred or a non-formulary/non-covered drug. Forms To request prior authorization using the Massachusetts Standard Form for Medication Prior Authorization Requests (eForm), click the link below: https://www.bluecrossma.org/medical- policies/sites/g/files/csphws2091/files/acquiadam- assets/023%20E%20Form%20medication%20prior%20auth%20instruction%20prn.pdf OR Print and fax, Massachusetts Standard Form for Medication Prior Authorization Requests #434 Specialty Blue Cross Blue Shield of Massachusetts (BCBSMA*) members (other than Medex®; Blue MedicareRx, Medicare Advantage plans that include prescription drug coverage) obtaining the medication from the Pharmacy benefit instead of the Medical benefit will be required to fill their prescriptions for medications listed as specialty at one of the providers in our retail specialty pharmacy network, see link below:

Link to Specialty Pharmacy List
Individual Consideration (for Atypical Patients) Our medical policies are written for most people with a given condition. Each policy is based on peer reviewed clinical evidence. We also take into consideration the needs of atypical patient populations and diagnoses.
If the coverage criteria outlined is unlikely to be clinically effective for the prescribed purpose, the health care provider may request an exception to cover the requested medication based on an individual’s unique clinical circumstances. This is also referred to as “individual consideration” or an “exception request.”
Some reasons why you may need us to make an exception include: therapeutic contraindications; history of adverse effects; expected to be ineffective or likely to cause harm (physical, mental, or adverse reaction).
To facilitate a thorough and prompt review of an exception request, we encourage the provider to include additional supporting clinical documentation with their request. This may

5 include: • Clinical notes or supporting clinical statements; • The name and strength of formulary alternatives tried and failed (if alternatives were tried) and specifics regarding the treatment failure, if applicable; • Clinical literature from reputable peer reviewed journals; • References from nationally recognized and approved drug compendia such as American Hospital Formulary Service® Drug Information (AHFS-DI), Lexi-Drug, Clinical Pharmacology, Micromedex or Drugdex®; and • References from consensus documents and/or nationally sanctioned guidelines

Providers may call, fax or mail relevant clinical information, including clinical references for individual patient consideration, to:

Blue Cross Blue Shield of Massachusetts Pharmacy Operations Department 25 Technology Place Hingham, MA 02043 Phone: 1-800-366-7778 Fax: 1-800-583-6289

Policy History Date Action 03/15/2026 Updated and clarified criteria requirements. 11/2025 Creation of new medical policy to group existing amyloidosis agents together that were previously housed in MP #033 and MP #049. Tegsedi was removed as it was dis continued by the manufacturer.

CPT Codes / HCPCs Codes / ICD Codes Inclusion or exclusion of a code does not constitute or imply member coverage or provider reimbursement. Please refer to the member’s contract benefits in effect at the time of service to determine coverage or non-coverage as it applies to an individual member.

Providers should report all services using the most up-to-date industry-standard procedure, revenue, and diagnosis codes, including modifiers where applicable.

The following codes are included below for informational purposes only; this is not an all-inclusive list. The above medical necessity criteria MUST be met for the following codes to be covered for Commercial Members: Managed Care (HMO and POS), PPO, and Indemnity: HCPCS Codes HCPCS codes: Code Description J0222 Injection, Patisiran, 0.1 mg (Onpattro) J0225 Injection, vutrisiran, 1 mg (Amvuttra) J3490 Unclassified drugs C9399 Unclassified drugs or biologicals The following ICD Diagnosis Codes are considered medically necessary when submitted with the HCPCS codes above if medical necessity criteria are met:

6 ICD-10 Diagnosis Codes ICD-10-CM Diagnosis codes: Code Description E85.1 Neuropathic heredofamilial amyloidosis E85.2 Heredofamilial amyloidosis, unspecified E85.4 Organ-limited amyloidosis E85.82 Wild-type transthyretin-related (ATTR) amyloidosis E85.9 Amyloidosis, unspecified I43 Cardiomyopathy in diseases classified elsewhere

References

1. Amvuttra ™ [package insert]. Cambridge, MA: Alnylam Pharmaceuticals, Inc.: 3/2025.
2. Onpattro ™ [package insert]. Cambridge, MA: Alnylam Pharmaceuticals, Inc.:1/2023.
3. Vyndaqel ® & Vyndamax ® [package insert]. New York, NY: Pfizer, Inc.: 8/2019.
4. Wainua. [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP, Inc.: 4/2025.
5. Gorevic PD. Overview of Amyloidosis. In: UpToDate, Lachmann, HJ (Ed), Wolters Kluwer. (Accessed on August 5, 2025.)
6. Fontana, M. Cardiac Amyloidosis: Epidemiology, Clinical Manifestations, and Diagnosis. In: UpToDate, Dardas, TF (Ed), Wolters Kluwer. (Accessed on August 5, 2025.)
7. Davalos, L and Dimachkie, MM. Neurologic Manifestations and Management of Systemic Amyloidosis. In: UpToDate, Goddeau RP (Ed), Wolters Kluwer. (Accessed on August 5, 2025.)