Centene Vutrisiran Coverage Update Prior Auth

Coverage Criteria for Vutrisiran (Amvuttra)

inv-01: Initial Therapy — hATTR polyneuropathy

Initial Approval — Polyneuropathy of Hereditary Transthyretin-Mediated Amyloidosis (ALL must be met)

Initial hATTR polyneuropathy criteria: 1. Diagnosis of hATTR with polyneuropathy; 2. Prescribed by or in consultation with a neurologist; 3. Age ≥ 18 years; 4. Documentation confirms presence of a transthyretin (TTR) mutation; 5. One of the following: (a) biopsy positive for amyloid deposits; or (b) medical justification for treatment despite negative or no biopsy; 6. Member has not had a prior liver transplant; 7. Amvuttra is not prescribed concurrently with Onpattro or Wainua; 8. Dose does not exceed 25 mg every 3 months.

inv-02: Initial Therapy — ATTR-CM

Initial Approval — Transthyretin Amyloid Cardiomyopathy (ALL must be met)

Initial ATTR-CM criteria: 1. Diagnosis of ATTR-CM; 2. Prescribed by or in consultation with a cardiologist; 3. Age ≥ 18 years; 4. Diagnosis supported by either: (a) tissue biopsy identifying transthyretin via mass spectrometry or immunohistochemistry AND (i) endomyocardial origin OR (ii) extracardiac origin with Echo/CMR/PET consistent with cardiac amyloidosis; OR (b) all of: (i) Echo/CMR/PET consistent with cardiac amyloidosis; (ii) cardiac uptake Grade 2 or 3 on SPECT using an accepted radiotracer (99mTc-DPD, 99mTc-PYP, or 99mTc-HMDP); (iii) negative laboratory testing for monoclonal protein (serum kappa/lambda ratio, serum immunofixation, urine immunofixation); 5. NYHA Class I–III heart failure; 6. If NYHA Class III, member does NOT have ATTR Disease Stage 3 (NT-proBNP > 3,000 ng/L and eGFR < 45 mL/min); 7. Member has either (a) ≥1 prior hospitalization for heart failure OR (b) current (within 30 days) clinical evidence of heart failure (e.g., exercise intolerance, unintentional weight loss, refractory volume overload, recurrent ventricular arrhythmias, hypotension with signs of inadequate perfusion); 8. Member has not had a prior liver transplant; 9. Amvuttra is not prescribed concurrently with Attruby or Onpattro; 10. For concurrent use with tafamidis (Vyndaqel/Vyndamax), provider must document ≥6 months tafamidis monotherapy with positive response and continued cardiac hospitalizations despite tafamidis; 11. Dose does not exceed 25 mg every 3 months.

Includes required imaging, SPECT specification per 2Q 2026 review.

inv-03: Continuation Therapy — hATTR polyneuropathy

Continued Therapy — hATTR polyneuropathy (ALL must be met)

Continued hATTR criteria: 1. Member meets one of the following: (a) currently receiving medication via Centene benefit or previously met initial approval criteria; or (b) currently receiving medication and enrolled in a state/product with continuity of care regulations; 2. Member is responding positively to therapy as evidenced by improvement in measures of polyneuropathy (motor strength, sensation, reflexes), quality of life, motor function, walking ability, or nutritional status; 3. Member has not had a prior liver transplant; 4. Amvuttra is not prescribed concurrently with Onpattro or Wainua; 5. If request is for a dose increase, new dose does not exceed 25 mg every 3 months.

inv-04: Continuation Therapy — ATTR-CM

Continued Therapy — ATTR-CM (ALL must be met)

Continued ATTR-CM criteria: 1. Member meets one of the following: (a) currently receiving medication via Centene benefit or previously met initial approval criteria; or (b) currently receiving medication and enrolled in a state/product with continuity of care regulations; 2. Member is responding positively to therapy, including improvement or stabilization in walking ability, nutrition (e.g., BMI), cardiac-related hospitalizations, or relevant cardiac procedures/laboratory tests (Holter, echo, ECG, BNP/NT-proBNP, troponin); 3. Amvuttra is not prescribed concurrently with Attruby or Onpattro; 4. If request is for a dose increase, new dose does not exceed 25 mg every 3 months.

Requests for uses that are not FDA‑approved and are not addressed by this policy will not be authorized unless the provider submits sufficient clinical documentation of efficacy and safety in accordance with the applicable off‑label use policies: CP.CPA.09 (Commercial), HIM.PA.154 (HIM/ICHRA), or CP.PMN.53 (Medicaid).

The policy criteria previously referenced Tegsedi as a prior‑agent exclusion; Tegsedi has been removed from the criteria because the agent is discontinued and is no longer included in prior‑agent restrictions.

Initial Therapy Rules and Dosing

inv-24: Initial therapy rules

Initial coverage requires meeting all indication-specific criteria.

Initial therapy nodes: Refer to coverage.criteria_sets for detailed initial approval requirements for hATTR polyneuropathy and ATTR-CM including specialist consultation, diagnostic confirmation, transplant status, concomitant therapy exclusions, and dosing limits.

inv-25: Initial Dosing

Dosing for initial therapy

Standard dosing: Administer 25 mg subcutaneously every three months.Maximum: 25 mg per 3 months

Continuation and Approval Durations

inv-26: Continuation rules

Criteria to continue therapy for patients already on vutrisiran

Continuation nodes: See coverage criteria for hATTR and ATTR-CM which require prior authorization history/continuity of care and demonstration of positive response or stability; dose limits apply (no more than 25 mg every 3 months).

inv-27: Continuation/Approval Durations

Historical approvals and continuation notes from annual reviews

Commercial approval duration clarified as 6 months or member renewal date, whichever is longer (as of 4Q 2022).

inv-28: Medicaid/HIM continuation

Medicaid/HIM continuation update

Provider Actions, Documentation, and Prior Authorization

Prior Authorization

Prior Authorization Required

Prior authorization required — Prior authorization is required. Provider must submit documentation (such as office chart notes, laboratory results, imaging, genetic test reports, and other relevant clinical information) demonstrating the member meets all approval criteria for the requested indication. Failure to provide supporting documentation may result in denial of the request.

Submit documentation verifying diagnosis and, where applicable, mutation confirmation (e.g., TTR mutation testing).
For polyneuropathy: documentation that treatment was prescribed by or in consultation with a neurologist and biopsy or medical justification per policy.
For cardiomyopathy: documentation that treatment was prescribed by or in consultation with a cardiologist and diagnostic support per policy (biopsy, imaging, and required lab testing to exclude monoclonal protein).
When requesting concurrent use with tafamidis (Vyndaqel/Vyndamax) for ATTR-CM, submit evidence of ≥6 months of tafamidis monotherapy with documented positive response and continued need (including ongoing cardiac-related hospitalizations) as required by the policy.
Do not include step-therapy restriction requiring that member has not received Onpattro, Tegsedi, or Wainua — this prior-agent restriction was removed in 2Q 2025.

Billing and Coding

HCPCS CodesHCPCS

J0225

Injection, vutrisiran, 1 mg

NT-proBNP / eGFR Threshold (ATTR Disease Stage 3)

ATTR Disease Stage 3 exclusionNT-proBNP > 3,000 ng/L AND eGFR < 45 mL/min

Context of useApplies when member has NYHA Class III heart failure for ATTR-CM initial approval criteria

Test definitions referencedNT-proBNP = N-terminal pro-B-type natriuretic peptide; eGFR = estimated glomerular filtration rate

Radionuclide Scan Specification for Cardiac Uptake

Required radionuclide imaging modalitySPECT (Single Photon Emission Computed Tomography) is specified for diagnosis by cardiac uptake

Accepted radiotracers (when using SPECT)99mTc-DPD, 99mTc-PYP, or 99mTc-HMDP as listed for Grade 2–3 cardiac uptake

Step Therapy and Concomitant Treatment Requirements

Evidence or condition required before concurrent use with tafamidis
Member has experienced and maintained a positive clinical response to tafamidis (Vyndaqel/Vyndamax) monotherapy following at least 6 months of continuous tafamidis treatment
Despite tafamidis monotherapy, member continues to require cardiac-related hospitalizations

Previous prior-agent restriction	Policy change / current status
Requirement that member has not received prior treatment with Onpattro, Tegsedi, or Wainua	Removed in 2Q 2025; prior-agent exclusion no longer required to allow alternative therapy (change applied per annual review)
Tegsedi-specific reference in prior-agent list	Tegsedi removed from criteria later due to market withdrawal (document notes Tegsedi removal in subsequent update)

Quantity Limits and Product Strength

Vutrisiran (Amvuttra) — Quantity Limit

Dose limit (quantity limit)25 mg per administration (maximum dose = 25 mg per 3 months)

Dosing intervalEvery 3 months (subcutaneous)

PresentationSingle-dose prefilled syringe: 25 mg/0.5 mL

vutrisiran (Amvuttra) — Strength Confirmation

Confirmed strength25 mg per single-dose syringe (25 mg/0.5 mL)

Maximum per dosing period25 mg every 3 months

Administration route

Definitions and Diagnostic Criteria

ATTR-CM — Definition

DefinitionCardiomyopathy of transthyretin-mediated amyloidosis

AbbreviationReferred to in policy as ATTR-CM

Clinical relevanceIndication covered for vutrisiran to reduce cardiovascular mortality, hospitalizations, and urgent heart failure visits

Diagnostic Confirmation — Amyloidosis

Primary confirmation methodTissue biopsy demonstrating amyloid deposits with Congo red staining and characteristic green birefringence

Genetic confirmationDNA sequencing of TTR is usually required to confirm hereditary mutation(s)

Background

Vutrisiran (Amvuttra) is an RNA interference therapeutic — a small interfering RNA (siRNA) directed at transthyretin (TTR) — designed to reduce production of TTR. It is indicated for adult patients with hereditary transthyretin‑mediated amyloidosis with polyneuropathy (hATTR) and transthyretin amyloid cardiomyopathy (ATTR‑CM), with diagnosis confirmation potentially involving biopsy, genotyping, and cardiac imaging/scintigraphy as appropriate.

Revision History and Policy Changes

2025-03-27added indication

Added new indication for transthyretin amyloid cardiomyopathy (ATTR-CM) per updated prescribing information during 2Q 2025 annual review.

2026-03-26removed agent

Removed Tegsedi from criteria as the agent is discontinued during 2Q 2026 annual review.

2026-03-26approval duration revisedLatest

Revised initial approval duration for Medicaid/HIM from 6 to 12 months during 2Q 2026 annual review.

OpenPayer

Clinical Policy: Vutrisiran (Amvuttra)