RetiredUnitedHealthcarePolicy CSLA2025D0072N

RNA-Targeted Therapies (Amvuttra and Onpattro) (for Louisiana Only)

UnitedHealthcare Louisiana Medical Benefit Drug Policy addressing medical necessity criteria, initial and continuation authorization, exclusions, applicable codes, and policy history for Amvuttra (vutrisiran) and Onpattro (patisiran) for treatment of cardiomyopathy and/or polyneuropathy related to transthyretin-mediated (ATTR) amyloidosis. The policy applied only to Louisiana and was retired effective April 1, 2026.

Policy Summary

PayerUnitedHealthcare

PolicyRNA-Targeted Therapies (Amvuttra and Onpattro) (for Louisiana Only)

Policy CodePolicy CSLA2025D0072N

Change TypeRetired; Coverage criteria added (10/01/2025) — retirement effective 04/01/2026

Effective DateOct 1, 2025

Next Review Date

Key ActionProvide required clinical documentation and obtain prior authorization/notification; ensure prescriptions follow FDA dosing and are by or in consultation with the appropriate specialist, and limit authorizations to 12 months.

POLICY UPDATE CHANGES

Policy retired effective April 1, 2026; Louisiana plan membership disenrolled on Apr. 1, 2026.

On 10/01/2025 coverage rationale updated to add Amvuttra as medically necessary for ATTR-CM with specific diagnostic and clinical criteria.

ICD-10 diagnosis codes E85.0, E85.4, and E85.82 were added to Applicable Codes.

Removed language indicating Amvuttra and Onpattro were unproven and not medically necessary for ATTR-CM.

2Indications addressed (cardiomyopathy, polyneuropathy)

4ICD-10 codes listed

2Drug J-codes listed

12 monthsAuthorization length (initial & continuation)

Coverage Summary

UnitedHealthcare Louisiana Medical Benefit Drug Policy CSLA2025D0072N addressed coverage for Amvuttra (vutrisiran) and Onpattro (patisiran) for transthyretin-mediated (ATTR) amyloidosis presenting as cardiomyopathy (ATTR-CM) and hereditary polyneuropathy (hATTR). The policy applied only to Louisiana and set medical necessity, initial and continuation authorization, exclusions, applicable codes, and policy history for these agents. The policy status is RETIRED effective April 1, 2026.

Initial Therapy Criteria

Amvuttra — Cardiomyopathy of wild-type (wtATTR) or hereditary (hATTR) ATTR (Initial Therapy)

Amvuttra is medically necessary when ALL of the following are met:

ALL of the following

Documentation of one of the following
- The patient has a pathogenic TTR mutation (e.g., V30M)
- Cardiac or noncardiac tissue biopsy demonstrating histologic confirmation of ATTR amyloid deposits
- All of the following
  - Echocardiogram or cardiac magnetic resonance imaging suggestive of amyloidosis
    May require prior authorization and notification
  - Radionuclide imaging (99mTc-DPD, 99mTc-PYP, or 99m Tc-HMDP) showing grade 2 or 3 cardiac uptakeGrade 2 or 3
    May require prior authorization and notification
  - Absence of light chain amyloidosis
Patient has New York Heart Association (NYHA) Functional Class I, II, or III heart failureNYHA I-III
Physician attests that the patient has an N-terminal pro-B-type natriuretic peptide (NT-proBNP) level that, when combined with signs and symptoms, is considered definitive for a diagnosis of ATTR-CM
Documentation of one of the following
- History of heart failure, with at least one prior hospitalization for heart failure
- Presence of signs and symptoms of heart failure (e.g., dyspnea, edema)
One of the following (treatment failure or intolerance pathway)
- Documentation of progressive worsening or an event resulting in hospitalization related to hATTR-mediated amyloidosis with cardiomyopathy (ATTR-CM) while on one of the following: Vyndaqel (tafamidis meglumine), Vyndamax (tafamidis), or Attruby (acoramidis)
- Documentation of intolerance or contraindication to both Vyndaqel (tafamidis meglumine) or Vyndamax (tafamidis) and Attruby (acoramidis)
Patient is not receiving Amvuttra in combination with any of the following: RNA interference agents (e.g., Onpattro (patisiran), Wainua (eplontersen), Tegsedi (inotersen)) or transthyretin stabilizers (e.g., Vyndaqel or Vyndamax)
Prescribed by or in consultation with a cardiologist
Dosing is in accordance with FDA prescribing information
Initial authorization is for no more than 12 months12 months

Amvuttra and Onpattro — Polyneuropathy of hATTR (Initial Therapy)

Amvuttra and Onpattro are medically necessary for polyneuropathy of hATTR when ALL required criteria are met:

ALL of the following

Both of the following
- Diagnosis of hATTR amyloidosis with polyneuropathy
- Documentation that the patient has a pathogenic TTR mutation (e.g., V30M)
Documentation of one of the following baseline scores
- Baseline polyneuropathy disability (PND) score ≤ IIIb≤ IIIb

Continuation Therapy Criteria

Amvuttra — Cardiomyopathy (Continuation of Therapy)

Continuation is allowable when ALL of the following are met:

ALL of the following

Patient has previously received treatment with Amvuttra for wtATTR or hATTR cardiomyopathy
Documentation that the patient has experienced a positive clinical response to Amvuttra (e.g., improved symptoms, quality of life, slowing of disease progression, decreased hospitalizations, etc.)
Documentation that the patient continues to have New York Heart Association (NYHA) Functional Class I, II, or III heart failureNYHA I-III
Patient is not receiving Amvuttra in combination with RNA interference agents (e.g., Onpattro (patisiran), Wainua (eplontersen), Tegsedi (inotersen)) or transthyretin stabilizers (e.g., Vyndaqel or Vyndamax)

Unproven / Not Medically Necessary

Amvuttra and Onpattro are considered unproven and not medically necessary for the following indications (policy previously stated):

ANY of the following

Sensorimotor or autonomic neuropathy not related to hATTR amyloidosis
Primary or leptomeningeal amyloidosis

Applicable Codes

Drug J-codesHCPCS

J0222	Injection, patisiran, 0.1 mg
J0225	Injection, vutrisiran, 1 mg

Applicable ICD-10 diagnosis codesICD-10

E85.0	Non-neuropathic heredofamilial amyloidosis
E85.1	Neuropathic heredofamilial amyloidosis
E85.4	Organ-limited amyloidosis
E85.82	Wild-type transthyretin-related (ATTR) amyloidosis

Provider Actions & Requirements

Prior Authorization

Prior authorization required

Initial and continuation authorizations are limited to no more than 12 months. Prior authorization/notification may be required for radionuclide imaging documentation of cardiac uptake. Prescriptions must follow FDA dosing and be prescribed by or in consultation with the appropriate specialist (cardiologist for ATTR‑CM; neurologist for polyneuropathy).

Documentation Required

Clinical documentation requirements

Provide documentation of: diagnosis (wtATTR or hATTR with cardiomyopathy, or hATTR with polyneuropathy as applicable); genetic, pathology, or imaging confirmation per policy criteria (pathogenic TTR mutation, tissue biopsy, or echocardiogram/CMR plus radionuclide imaging showing grade 2–3 uptake and absence of light‑chain amyloidosis); baseline and/or continued functional scores (PND, NIS, FAP stage, KPS) as specified; evidence of a positive clinical response for continuation (e.g., improved symptoms, QoL, slowed progression, decreased hospitalizations); for ATTR‑CM, history of heart failure hospitalization or signs/symptoms of heart failure; and physician attestation of NT‑proBNP level combined with signs/symptoms to support the diagnosis.

Clinical Evidence

Amvuttra and Onpattro are transthyretin-directed small interfering RNAs (siRNAs) that reduce circulating TTR by targeting TTR mRNA. Clinical development includes HELIOS-B for vutrisiran in ATTR cardiomyopathy, which demonstrated a reduction in death and recurrent cardiovascular events, and APOLLO for patisiran in hATTR polyneuropathy, which showed significant improvement in neuropathy scores (mNIS+7). These trial results underlie the policy’s coverage rationale and the October 1, 2025 changes that established medical necessity criteria for ATTR-CM and polyneuropathy.

Background & Definitions

Amvuttra (vutrisiran) and Onpattro (patisiran) are double-stranded small interfering RNAs (siRNAs) that target a conserved TTR mRNA sequence to degrade TTR transcript and reduce serum TTR and tissue deposits; Amvuttra is formulated in lipid nanoparticles directed to the liver, the primary source of circulating TTR. The HELIOS-B phase 3 trial established vutrisiran’s efficacy in ATTR cardiomyopathy, showing a lower risk of death and recurrent cardiovascular events (hazard ratio 0.72; 95% CI 0.56–0.93; p=0.01) and benefits in functional measures such as 6-minute walk distance and KCCQ-OS. The APOLLO phase 3 trial demonstrated patisiran’s efficacy in hATTR polyneuropathy with a large LS mean improvement in mNIS+7 at 18 months (LS mean change −33.99 vs placebo; p=9.26×10−24), along with improvements in quality of life and cardiac parameters in subgroup analyses. Vutrisiran’s polyneuropathy study also showed significant mNIS+7 improvement versus an external placebo at Month 9 (difference −17.0; 95% CI −21.8 to −12.2; p<0.001).

Term	Definition
ATTR-CM	Transthyretin-mediated amyloidosis with cardiomyopathy
PND score	Polyneuropathy disability score; criterion uses ≤ IIIb
NIS	Neuropathy Impairment Score; criterion uses ≥ 5 and ≤ 130
KPS	Karnofsky Performance Status; criterion uses ≥ 60%

Revision History

2025-10-01policy_revised

Coverage rationale updated to add Amvuttra (vutrisiran) as medically necessary for ATTR-CM with specific diagnostic and clinical criteria (diagnosis of wtATTR or hATTR with cardiomyopathy; documentation via pathogenic TTR mutation, biopsy, or imaging with grade 2–3 radionuclide cardiac uptake and absence of light chain amyloidosis; NYHA class I–III; NT-proBNP attestation; heart failure history/signs; treatment-failure or intolerance pathways for tafamidis/acoramidis; combination therapy exclusions; specialist prescribing requirement; and 12-month authorization limit).

2025-10-01codes_added

ICD-10 diagnosis codes E85.0, E85.4, and E85.82 were added to Applicable Codes.

2025-10-01policy_revised

Policy Summary

PayerUnitedHealthcare

PolicyRNA-Targeted Therapies (Amvuttra and Onpattro) (for Louisiana Only)

Policy CodePolicy CSLA2025D0072N

Change TypeRetired; Coverage criteria added (10/01/2025) — retirement effective 04/01/2026

Effective DateOct 1, 2025

Next Review Date

On This Page

Baseline familial amyloid polyneuropathy (FAP) Stage 1 or 2

Baseline neuropathy impairment score (NIS) ≥ 5 and ≤ 130NIS ≥5 and ≤130

Baseline Karnofsky performance status (KPS) score ≥ 60%KPS ≥60%

Presence of clinical signs and symptoms of the disease (e.g., peripheral sensorimotor polyneuropathy, autonomic neuropathy, motor disability, etc.)

Patient has not had a liver transplant

Medication-specific combination exclusions or alternative pathway

For Amvuttra: patient is not receiving in combination with RNA interference agents or transthyretin stabilizers
For Onpattro: patient is not receiving in combination with RNA interference agents (e.g., Amvuttra) or transthyretin stabilizers
Documentation of intolerance or contraindication to both Vyndaqel (tafamidis) and Attruby (acoramidis)

Prescribed by or in consultation with a neurologist

Dosing is in accordance with FDA prescribing information

Initial authorization is for no more than 12 months12 months

Prescribed by or in consultation with a cardiologist

Dosing per FDA prescribing information

Authorization is for no more than 12 months12 months

Amvuttra and Onpattro — Polyneuropathy of hATTR (Continuation of Therapy)

Continuation when ALL of the following are met:

ALL of the following

Patient has previously received Amvuttra or Onpattro
Documentation of continued baseline scores
- Patient continues to have a PND score ≤ IIIb≤ IIIb
- Patient continues to have FAP stage 1 or 2FAP 1 or 2
- Patient continues to have a NIS score ≥ 5 and ≤ 130NIS ≥5 and ≤130
- Patient continues to have a KPS score ≥ 60%KPS ≥60%
Documentation that the patient has experienced a positive clinical response to Amvuttra or Onpattro (e.g., improved neurologic impairment, motor function, quality of life, slowing of disease progression, etc.)
Medication-specific combination exclusions
- For Amvuttra: patient is not receiving in combination with RNA interference agents or transthyretin stabilizers
- For Onpattro: patient is not receiving in combination with RNA interference agents (e.g., Amvuttra) or transthyretin stabilizers
Prescribed by or in consultation with a neurologist
Dosing per FDA prescribing information
Authorization is for no more than 12 months12 months

Diagnosis
Genetic / pathology / imaging confirmation (pathogenic TTR mutation, biopsy, or echocardiogram/CMR + radionuclide imaging grade 2–3 and absence of light‑chain amyloidosis)
Baseline and/or continued functional scores: PND, NIS, FAP stage, KPS
Evidence of positive clinical response for continuation
History of HF hospitalization or signs/symptoms of HF (e.g., dyspnea, edema)
Physician attestation of NT‑proBNP when combined with signs/symptoms

Denial Risk

Combination therapy exclusion

Claims may be denied when Amvuttra is used in combination with other RNA interference agents or with transthyretin stabilizers. Ensure exclusion criteria are met to avoid denials; affected J‑codes include J0225 (vutrisiran) and J0222 (patisiran).

Billing Rule

Use appropriate J-code

Report the appropriate HCPCS J‑code for the administered product according to the billed dose: J0225 for vutrisiran and J0222 for patisiran.

Removed prior language indicating Amvuttra and Onpattro were unproven and not medically necessary for ATTR-CM (policy changed from negative coverage stance to affirmative coverage for Amvuttra under defined criteria).

2026-04-01policy_retiredLatest

Policy retired effective April 1, 2026; Louisiana plan membership disenrolled on Apr. 1, 2026.