ModifiedUnitedHealthcarePolicy CSOH2025D0072.C

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

Ohio-only UnitedHealthcare Medical Benefit Drug Policy governing medical necessity criteria, initial and continuation authorization requirements, and applicable billing codes for Amvuttra (vutrisiran) and Onpattro (patisiran) to treat cardiomyopathy and polyneuropathy related to transthyretin-mediated (ATTR) amyloidosis.

Policy Summary

PayerUnitedHealthcare

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

Policy CodePolicy CSOH2025D0072.C

Change TypeModified coverage stance for Amvuttra in ATTR‑CM; added and clarified criteria

Effective DateAug 1, 2025

Next Review Date

Key ActionDocument diagnosis, mutation or biopsy/imaging confirmation, functional/neurologic baseline and ongoing scores, specialist consultation, and request prior authorization for up to 12 months as required.

POLICY UPDATE CHANGES

Removed language indicating Amvuttra and Onpattro are unproven and not medically necessary for ATTR-CM and added criteria indicating Amvuttra is medically necessary for treatment of cardiomyopathy of wtATTR or hATTR when specific criteria are met.

Added ICD-10 diagnosis codes E85.0, E85.4, and E85.82 to applicable codes.

Clarified continuation criteria for Amvuttra and Onpattro for polyneuropathy and cardiomyopathy including required documentation of positive clinical response and ongoing functional class or neurologic scores.

2Indications covered (cardiomyopathy, polyneuropathy)

12 monthsMax authorization duration

J0225,J0222Primary J-codes

Coverage Summary

This is an Ohio-only UnitedHealthcare Medical Benefit Drug Policy (Policy No. CSOH2025D0072.C, effective August 1, 2025) governing medical necessity criteria, initial and continuation authorization requirements, and applicable billing codes for Amvuttra (vutrisiran) and Onpattro (patisiran) to treat transthyretin-mediated (ATTR) amyloidosis presenting as cardiomyopathy (wild-type and hereditary ATTR-CM) and polyneuropathy of hereditary ATTR (hATTR). Coverage stance is mixed (both medically necessary under specified criteria and limited/unproven for some uses), with initial and continuation authorizations generally limited to no more than 12 months and primary J-codes J0225 and J0222 referenced.

Amvuttra — Cardiomyopathy (Initial Therapy)

Amvuttra (vutrisiran) — Cardiomyopathy (wtATTR or hATTR) - Initial Therapy

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

ALL of the following

Diagnosis of wild-type or hereditary ATTR-mediated amyloidosis with cardiomyopathy (ATTR-CM)
Documentation (ONE of)
- 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
  - Radionuclide imaging (99mTc-DPD, 99mTc-PYP, or 99mTc-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, II, or III
Physician attests that the patient has an NT-proBNP level that, when combined with signs and symptoms, is considered definitive for a diagnosis of ATTR-CM
Documentation of cardiac disease (ONE of)
- 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)
Evidence of progression or intolerance (ONE of)
- Documentation of progressive worsening or an event resulting in hospitalization related to hATTR-mediated amyloidosis with cardiomyopathy (ATTR-CM) while on 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 RNA interference agents (e.g., Onpattro/patisiran, Wainua/eplontersen, Tegsedi/inotersen) or transthyretin stabilizers (e.g., Vyndaqel/Vyndamax)
Prescribed by or in consultation with a cardiologist
Dosing is in accordance with the FDA prescribing information
Initial authorization is for no more than 12 months12 months

Amvuttra — Cardiomyopathy (Continuation Therapy)

Amvuttra (vutrisiran) — Cardiomyopathy (wtATTR or hATTR) - Continuation Therapy

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

ALL of the following

Patient has previously received treatment with Amvuttra for cardiomyopathy of wtATTR or hATTR amyloidosis
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 NYHA Functional Class I, II, or III heart failureNYHA I, II, or III

Amvuttra and Onpattro — Polyneuropathy of hATTR (Initial Therapy)

Amvuttra (vutrisiran) and Onpattro (patisiran) — Polyneuropathy of hATTR Amyloidosis - Initial Therapy

Medically necessary for treatment of polyneuropathy of hATTR when ALL of the following 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)
Neurologic baseline criteria (ONE of)
- Baseline polyneuropathy disability (PND) score ≤ IIIb≤ IIIb

Amvuttra and Onpattro — Polyneuropathy of hATTR (Continuation Therapy)

Amvuttra (vutrisiran) and Onpattro (patisiran) — Polyneuropathy of hATTR Amyloidosis - Continuation Therapy

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

ALL of the following

Patient has previously received treatment with Amvuttra or Onpattro
Ongoing neurologic status (ONE of)
- Patient continues to have a PND score ≤ IIIb≤ IIIb
- Patient continues to have a FAP stage 1 or 2Stage 1 or 2

Not Medically Necessary / Unproven

Amvuttra and Onpattro are considered unproven and not medically necessary for the following:

ANY of the following

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

Applicable Codes

Drug HCPCS/J-codeHCPCSCovered

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

ICD-10 Diagnosis Codes (added)ICD-10Covered

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 require prior authorization. Initial and continuation authorizations are limited to no more than 12 months. Radionuclide imaging (99mTc‑DPD, 99mTc‑PYP, or 99mTc‑HMDP) showing grade 2 or 3 cardiac uptake may require prior authorization and notification; requests are evaluated for medical necessity per Ohio Administrative Code 5160-1-01.

Documentation Required

Clinical documentation required

Provider must document the diagnosis and supporting clinical information, including: diagnosis of hATTR or wt/hATTR as applicable; evidence of a pathogenic TTR mutation or tissue biopsy/imaging confirmation with documented absence of light‑chain (AL) amyloidosis; New York Heart Association (NYHA) class (I, II, or III) and an NT‑proBNP attestation when used for ATTR‑CM; prior heart failure hospitalizations or signs/symptoms of heart failure; and baseline and/or ongoing neurologic scores as applicable (PND, FAP stage, NIS, KPS).

Clinical Evidence

Amvuttra (vutrisiran) and Onpattro (patisiran) are transthyretin-directed double-stranded small interfering RNAs (siRNAs) formulated to reduce TTR protein levels by degrading conserved TTR mRNA sequences and lowering circulating and tissue TTR. Phase 3 trials are cited: HELIOS-B (vutrisiran) demonstrated reduced risk of death and recurrent cardiovascular events and improvements in functional measures (e.g., 6-minute walk test, KCCQ-OS) in patients with ATTR cardiomyopathy, and APOLLO (patisiran) showed significant improvement in neuropathy (mNIS+7) and related secondary endpoints in hATTR polyneuropathy. The policy summarizes safety and efficacy findings from these trials (including reductions in mortality/CV events with vutrisiran and improvements in neurologic impairment and quality of life with patisiran) without additional interpretation.

Background & Definitions

Amvuttra and Onpattro are siRNA therapies that target transthyretin mRNA to lower TTR; Amvuttra is FDA-indicated for hATTR polyneuropathy and for cardiomyopathy of wild-type or hereditary ATTR to reduce cardiovascular mortality and hospitalizations, while Onpattro is FDA-indicated for the polyneuropathy of hATTR.

Term	Definition
ATTR-CM
Transthyretin-mediated amyloidosis with cardiomyopathy
PND
Polyneuropathy Disability score
NIS
Neuropathy Impairment Score
KPS
Karnofsky Performance Status
NYHA
New York Heart Association Functional Classification

Key Thresholds & Scores

Revision History

2025-08-01policy_revisedLatest

Material — Added detailed initial and continuation medical necessity criteria for Amvuttra (vutrisiran) for treatment of cardiomyopathy of wild-type (wtATTR) or hereditary (hATTR) transthyretin-mediated amyloidosis (ATTR-CM), including diagnostic requirements (pathogenic TTR mutation, biopsy, or imaging with echocardiogram/CMR and radionuclide imaging grade 2–3 uptake with absence of light chain amyloidosis), NYHA class I–III, NT‑proBNP attestation, documentation of heart failure history or signs/symptoms, evidence of progression or intolerance to tafamidis or acoramidis, cardiologist prescribing requirement, exclusion of combination with other RNAi agents or stabilizers, dosing per FDA, and initial authorization limit of ≤12 months.

2025-08-01policy_revisedLatest

Material — Removed prior language stating Amvuttra and Onpattro were 'unproven and not medically necessary' for ATTR‑CM and replaced it with explicit determination that Amvuttra is medically necessary for ATTR‑CM when specific criteria are met.

Policy Summary

PayerUnitedHealthcare

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

Policy CodePolicy CSOH2025D0072.C

Change TypeModified coverage stance for Amvuttra in ATTR‑CM; added and clarified criteria

Effective DateAug 1, 2025

Next Review Date

On This Page

Patient is not receiving Amvuttra in combination with RNA interference agents or transthyretin stabilizers

Examples listed in policy

Prescribed by or in consultation with a cardiologist

Dosing is in accordance with the FDA prescribing information

Authorization is for no more than 12 months12 months

Baseline familial amyloid polyneuropathy (FAP) Stage 1 or 2Stage 1 or 2

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

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

Product-specific combination exclusions (ONE of)

For Amvuttra, patient is not receiving it in combination with other RNA interference agents (e.g., Onpattro/patisiran, Wainua/eplontersen, Tegsedi/inotersen) or transthyretin stabilizers (e.g., Vyndaqel/Vyndamax)
For Onpattro, patient is not receiving it in combination with other RNA interference agents (e.g., Amvuttra/vutrisiran, Wainua/eplontersen, Tegsedi/inotersen) or transthyretin stabilizers (e.g., Vyndaqel/Vyndamax)

Alternative pathway (ONE of)

Documentation of intolerance or contraindication to both Vyndaqel (tafamidis meglumine) or Vyndamax (tafamidis) AND Attruby (acoramidis)

Prescribed by or in consultation with a neurologist

Dosing is in accordance with the FDA prescribing information

Initial authorization is for no more than 12 months12 months

Patient continues to have a NIS score ≥ 5 and ≤ 130≥5 and ≤130

Patient continues to have a KPS score ≥ 60%≥ 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.)

Product-specific combination exclusions (ONE of)

For Amvuttra, patient is not receiving it in combination with other RNA interference agents or transthyretin stabilizers
For Onpattro, patient is not receiving it in combination with other RNA interference agents or transthyretin stabilizers

Prescribed by or in consultation with a neurologist

Dosing is in accordance with the FDA prescribing information

Authorization is for no more than 12 months12 months

Diagnosis
Pathogenic TTR mutation or biopsy/imaging confirmation (absence of light‑chain amyloidosis)
NYHA class (I, II, or III) and NT‑proBNP attestation (for ATTR‑CM)
Prior hospitalizations or signs/symptoms of heart failure
Baseline and/or ongoing neurologic scores: PND, FAP stage, NIS, KPS (as applicable)

Documentation Required

Specialist prescribing requirement

Specialist involvement is required: prescriptions for Amvuttra for cardiomyopathy must be prescribed by or in consultation with a cardiologist; prescriptions for Amvuttra or Onpattro for polyneuropathy must be prescribed by or in consultation with a neurologist.

Billing Rule

Drug dosing adherence

Dosing for Amvuttra (J0225) and Onpattro (J0222) must adhere to the U.S. Food and Drug Administration prescribing information.

Denial Risk

Combination therapy exclusion

Claims may be denied if Amvuttra (J0225) or Onpattro (J0222) are used in combination with other RNA interference agents (e.g., the listed agents such as Onpattro/patisiran, Wainua/eplontersen, Tegsedi/inotersen) or transthyretin stabilizers (e.g., Vyndaqel/Vyndamax); product‑specific combination exclusions are stated in the policy.

2025-08-01policy_clarifiedLatest

Material — Clarified continuation criteria for Amvuttra (cardiomyopathy) and for Amvuttra/Onpattro (polyneuropathy) requiring prior receipt of therapy, documentation of positive clinical response, ongoing NYHA class I–III (cardiac) or continued acceptable neurologic scores (PND ≤ IIIb, FAP Stage 1–2, NIS 5–130, or KPS ≥60%), continued specialist prescribing, product-specific combination exclusions, dosing per FDA, and authorization renewals limited to ≤12 months.

2025-08-01codes_addedLatest

Non-material — Added ICD-10 diagnosis codes E85.0, E85.4, and E85.82 to the policy's applicable codes (also lists J0225 and J0222 as primary drug J-codes).