CurrentAnthemPolicy CC-0217

Amvuttra (vutrisiran)

Clinical coverage and prior authorization criteria for Amvuttra (vutrisiran) for treatment of polyneuropathy and cardiomyopathy due to transthyretin-mediated amyloidosis under the medical benefit.

Policy Summary

PayerAnthem

PolicyAmvuttra (vutrisiran) clinical coverage and prior authorization criteria

Policy CodePolicy CC-0217

Change TypeRevised — material changes include added continuation diagnosis criteria and new cardiomyopathy indication

Effective Date10/01/2025

Next Review Date08/15/2026

Key ActionObtain prior authorization and submit documentation of diagnosis and required diagnostic confirmation (TTR genotyping for polyneuropathy; biopsy or radionuclide scintigraphy plus absence of monoclonal protein for cardiomyopathy).

SourceLink

POLICY UPDATE CHANGES

Add diagnosis criteria to continuation criteria and remove renal and hepatic exclusions.

Add approval for new indication for cardiomyopathy.

Quantity limit specified as 1 syringe per 3 months (25 mg/0.5 mL).

1 syringe/3moproduct quantity limit

J0225HCPCS

E85.1, E85.4ICD-10 diagnoses

q3 monthsadministration freq

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Coverage Criteria for Amvuttra (vutrisiran)

Initial Therapy - Polyneuropathy

Covered when ALL of the following are met

ALL of the following

Diagnosis: Individual has a diagnosis of hereditary transthyretin (hATTR) amyloidosis or familial amyloid polyneuropathy (FAP)
Genotyping: Documentation of TTR mutation verified by genotyping (NCT 03759379)
Severity: Documentation of associated mild to moderate polyneuropathy

Continuation Therapy - Polyneuropathy

Covered when ALL of the following are met

ALL of the following

Diagnosis: Individual has a diagnosis of polyneuropathy of hereditary transthyretin (hATTR) amyloidosis
Genotyping: Documentation of TTR mutation verified by genotyping (NCT 03759379)
Response: Documentation of clinically significant improvement or stabilization in signs and symptoms (including but not limited to improved ambulation, improvement in neurologic symptom burden, improvement in activities of daily living)
Continuation criterion

Initial Therapy - Cardiomyopathy

Covered when ALL of the following are met

ALL of the following

Diagnosis: Individual has a diagnosis of wild-type or hereditary transthyretin amyloid cardiomyopathy
Diagnostic confirmation: Diagnosis demonstrated by endomyocardial or extracardiac biopsy OR radionuclide scintigraphy (99mTc-PYP/DPD/HMDP) grade 2 or 3 uptake plus absence of monoclonal protein on serum free light chain assay and serum and urine immunofixation
References: Dorbala 2021, Kittleson 2023
NYHA class: Individual is using for treatment of New York Heart Association class I, II or III heart failure symptomsNYHA I-III

Continuation Therapy - Cardiomyopathy

Covered when ALL of the following are met

ALL of the following

Diagnosis: Individual has a diagnosis of wild-type or hereditary transthyretin amyloid cardiomyopathy
Diagnostic confirmation: Diagnosis demonstrated by endomyocardial or extracardiac biopsy OR radionuclide scintigraphy (99mTc-PYP/DPD/HMDP) grade 2 or 3 uptake plus absence of monoclonal protein on serum free light chain assay and serum and urine immunofixation
References: Dorbala 2021, Kittleson 2023
Response: Documentation of clinically significant improvement or stabilization in signs and symptoms (including but not limited to reduction in hospitalizations or urgent heart failure visits, improvement or stabilization in 6-Minute Walk Test, improvement in symptom burden or frequency)
Continuation criterion

Use of Amvuttra (vutrisiran) is not approved for individuals with a history of liver or heart transplantation. It is also not approved for individuals who have sensorimotor or autonomic neuropathy that is not related to hATTR amyloidosis (for example, neuropathy due to monoclonal gammopathy or autoimmune disease). Concurrent use of Amvuttra with other transthyretin-directed therapies (including Attruby, Onpattro, Tegsedi, Vyndaqel, Vyndamax, or Wainua) is not permitted. Requests may also be denied when the policy’s diagnostic or continuation criteria are not met.

Requests for Amvuttra (vutrisiran) that do not meet the specified diagnostic or continuation criteria for the indicated uses are not approved. Prior authorization is required and approval is contingent on documentation satisfying the applicable diagnostic confirmation and response or stabilization criteria for the requested indication.

Initial Therapy

Initial therapy

Covered when ALL of the following are met

ALL of the following

Diagnosis documented: Diagnosis of hATTR polyneuropathy or ATTR cardiomyopathy as applicable
Required diagnostic testing: For polyneuropathy: TTR genotyping verifying a pathogenic mutation; For cardiomyopathy: diagnostic confirmation by endomyocardial or extracardiac biopsy OR radionuclide scintigraphy (99mTc-PYP/DPD/HMDP) grade 2–3 plus absence of monoclonal protein on serum free light chain assay and serum and urine immunofixation
References: NCT 03759379; Dorbala 2021, Kittleson 2023
Severity/NYHA: Polyneuropathy: mild to moderate disease; Cardiomyopathy: NYHA class I–III for treatment

Continuation Therapy

Continuation criteria

Covered when ALL of the following are met

ALL of the following

Diagnosis documented: Diagnosis of hATTR polyneuropathy or ATTR cardiomyopathy as applicable
Required diagnostic confirmation: Polyneuropathy: TTR genotyping; Cardiomyopathy: biopsy OR radionuclide scintigraphy grade 2–3 plus absence of monoclonal protein on serum and urine testing
Clinical response: Documentation of clinically significant improvement or stabilization in signs and symptoms compared with baseline (examples: improved ambulation, reduced neurologic symptom burden, improved activities of daily living; or reduced hospitalizations/urgent HF visits, improvement/stability in 6‑Minute Walk Test, improved symptom burden)
Continuation requirement

Coding and Diagnosis Codes

HCPCSHCPCSCovered

J0225

Injection, vutrisiran, 1 mg [Amvuttra]

ICD-10 DiagnosisICD-10

E85.1	Neuropathic heredofamilial amyloidosis [transthyretin-related (ATTR) familial amyloid polyneuropathy]
E85.4	Organ-limited amyloidosis [Transthyretin-related (ATTR) familial amyloid cardiomyopathy]

NYHA class for cardiomyopathy use

NYHA class allowedI–III

Use contextApplied for treatment of ATTR cardiomyopathy (wild-type or hereditary) per cardiomyopathy criteria

Source guidanceClinical trial and guideline populations included NYHA class I, II, or III

Provider Requirements, Documentation, and Billing

Prior Authorization

Prior Authorization and Billing

Prior authorization is required for Amvuttra (vutrisiran). Submit clinical documentation that supports the FDA‑approved indication and the applicable medical necessity criteria for polyneuropathy or cardiomyopathy of transthyretin‑mediated (ATTR) amyloidosis.

Prior authorization required before initiation or continuation of therapy.
HCPCS J0225 — Injection, vutrisiran, 1 mg [Amvuttra] for billing.

Denial Risk

Concurrent Therapy Restriction

Do not approve requests when there is a history of liver or heart transplantation, neuropathy not related to hATTR, or when the member is receiving another transthyretin‑directed therapy. Concurrent use with other transthyretin‑directed agents is not allowed.

Concurrent therapy restriction: disallowed with Attruby, Onpattro, Tegsedi, Vyndaqel/Vyndamax, or Wainua.

Step Therapy and Treatment Restrictions

Step	Requirement / Notes
1	Do not use in combination with other specified transthyretin-directed therapies (Attruby, Onpattro, Tegsedi, Vyndaqel, Vyndamax, Wainua). No additional step therapy sequence or failure criteria specified.

Quantity Limits

Quantity limit

ProductAmvuttra (vutrisiran) 25 mg/0.5 mL syringe

Quantity limit1 syringe per 3 months

Unit of measure25 mg / 0.5 mL syringe

Site of Care and Administration

Note

Office administration — subcutaneous injection by provider

Amvuttra must be administered subcutaneously by a healthcare provider in an office or clinical setting.

Given as a subcutaneous injection by a healthcare provider every three months.

Background

Transthyretin-mediated amyloidosis is a progressive, multisystem disease in which misfolded transthyretin forms amyloid fibrils that deposit in organs including peripheral nerves and the heart, producing clinical syndromes of polyneuropathy and cardiomyopathy. Amvuttra (vutrisiran) is an siRNA therapeutic indicated to treat polyneuropathy of hereditary transthyretin-mediated (hATTR) amyloidosis and to treat wild-type or hereditary transthyretin amyloid cardiomyopathy in adults. For cardiomyopathy the diagnosis must be demonstrated by biopsy or by radionuclide scintigraphy (99mTc-PYP/DPD/HMDP) with grade 2–3 uptake plus absence of monoclonal protein; treatment is for patients with NYHA class I–III symptoms. Amvuttra is administered as a subcutaneous injection by a healthcare provider and requires monitoring per the prescribing information.

Definitions

hATTR amyloidosis — key points

DefinitionHereditary transthyretin-mediated (hATTR) amyloidosis: transthyretin amyloidosis caused by TTR gene mutations leading to systemic amyloid deposition and polyneuropathy (formerly called familial amyloid polyneuropathy, FAP)

Typical manifestationsProgressive polyneuropathy with symptoms such as muscle weakness, difficulty ambulating, impaired balance, and autonomic features

Diagnostic requirement (policy-specific)TTR mutation confirmed by genotyping for polyneuropathy indication

Exclusions notedPolicy excludes use in individuals with liver or heart transplant and neuropathy not related to hATTR

ATTR cardiomyopathy — definition and clinical description

DefinitionATTR cardiomyopathy: cardiac manifestation of transthyretin-mediated amyloidosis (wild-type or hereditary) characterized by amyloid deposition in the heart leading to heart failure and conduction issues