ModifiedColorado Rocky Mountain Health PlansPolicy 2026D0072O

RNA-Targeted Therapies (Amvuttra and Onpattro)

Defines UnitedHealthcare Commercial and Individual Exchange medical benefit coverage criteria, prior authorization and continuation requirements for Amvuttra (vutrisiran) and Onpattro (patisiran) for treatment of cardiomyopathy (wtATTR and hATTR) and polyneuropathy of hATTR amyloidosis, including applicable codes and contraindicated/unproven indications.

Policy Summary

PayerColorado Rocky Mountain Health Plans

PolicyRNA-Targeted Therapies (Amvuttra and Onpattro)

Policy CodePolicy 2026D0072O

Change TypeTemplate update / administrative

Effective DateJun 1, 2026

Next Review Date

Key ActionObtain prior authorization and document diagnosis, genetic or biopsy confirmation (or imaging criteria), required severity measures, specialist consultation, and positive clinical response for continuation; authorizations limited to 12 months.

POLICY UPDATE CHANGES

Template Update: Transferred content to shared policy template applying to both UnitedHealthcare Commercial and Individual Exchange benefit plans; added Application section and updated CMS and References.

2Drugs addressed (Amvuttra, Onpattro)

2Indications covered (ATTR cardiomyopathy, hATTR polyneuropathy)

2Specialist prescribers required (cardiology, neurology)

Coverage Summary

This policy defines UnitedHealthcare Commercial and Individual Exchange medical benefit coverage for RNA-targeted therapies Amvuttra (vutrisiran) and Onpattro (patisiran). The coverage stance is covered_with_criteria, with medical necessity criteria, prior authorization, and continuation requirements that apply to treatment of transthyretin-mediated cardiomyopathy (both wild-type and hereditary ATTR-CM) and the polyneuropathy of hereditary ATTR (hATTR).

The policy references FDA indications: Amvuttra is indicated for the polyneuropathy of hATTR and for cardiomyopathy of wild-type or hereditary ATTR to reduce cardiovascular mortality, cardiovascular hospitalizations, and urgent heart failure visits; Onpattro is indicated for the polyneuropathy of hATTR. The intent is to authorize these agents when the specified diagnostic, severity, specialist-prescriber, dosing, and combination-therapy exclusion criteria are met, and to limit initial and continuation authorizations to no more than 12 months per the policy.

Initial Therapy — Amvuttra for ATTR‑CM

Amvuttra — Cardiomyopathy of wtATTR or hATTR (Initial Therapy)

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

ALL of the following

Documentation of one of the following
- Diagnosis of wild-type or hereditary ATTR-mediated amyloidosis with cardiomyopathy (ATTR-CM).
- The patient has a pathogenic TTR mutation (e.g., V30M).
- Cardiac or noncardiac tissue biopsy demonstrating histologic confirmation of ATTR amyloid deposits.
- Or 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 uptake.grade 2 or 3 cardiac uptake
    May require prior authorization and notification.
  - Absence of light chain amyloidosis.
One of the following cardiac clinical features
- 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 disease course or intolerance criteria
- Documentation of progressive worsening or an event resulting in hospitalization related to hATTR-mediated amyloidosis with cardiomyopathy (ATTR-CM) while on Vyndaqel (tafamidis meglumine) or Vyndamax (tafamidis) or Attruby (acoramidis).
- Documentation of intolerance or contraindication to both Vyndaqel/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 U.S. Food and Drug Administration prescribing information.
Initial authorization is for no more than 12 months.12 months

Continuation of Therapy — Amvuttra for ATTR‑CM

Amvuttra — Cardiomyopathy of wtATTR or hATTR (Continuation of Therapy)

Covered when ALL of the following are met:

ALL of the following

Patient has previously received treatment with Amvuttra for ATTR-CM.
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 failure.NYHA I–III
Patient is not receiving Amvuttra in combination with RNA interference agents or transthyretin stabilizers.
Prescribed by or in consultation with a cardiologist.
Dosing is in accordance with the FDA prescribing information.
Authorization is for no more than 12 months.12 months

Initial Therapy — Amvuttra and Onpattro for hATTR Polyneuropathy

Amvuttra and Onpattro — Polyneuropathy of hATTR (Initial Therapy)

Amvuttra and Onpattro are medically necessary for hATTR polyneuropathy when ALL of the following are met:

ALL of the following

Diagnosis and genetic requirement
- Diagnosis of hATTR amyloidosis with polyneuropathy.
- Documentation that the patient has a pathogenic TTR mutation (e.g., V30M).
Baseline severity — one of
- Patient has a baseline polyneuropathy disability (PND) score ≤ IIIb.≤ IIIb
- Patient has a baseline familial amyloid polyneuropathy (FAP) Stage 1 or 2.Stage 1 or 2
- Patient has a baseline neuropathy impairment score (NIS) ≥ 5 and ≤ 130.≥5 and ≤130
- Patient has a 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.
Combination therapy exclusions (drug-specific)
- For Amvuttra
  - Patient is not receiving Amvuttra in combination with other RNA interference agents (e.g., Onpattro/patisiran, Wainua/eplontersen, Tegsedi/inotersen).
  - Patient is not receiving Amvuttra in combination with transthyretin stabilizers (e.g., Vyndaqel/Vyndamax).
- For Onpattro
  - Patient is not receiving Onpattro in combination with other RNA interference agents (e.g., Amvuttra/vutrisiran, Wainua/eplontersen, Tegsedi/inotersen).
  - Patient is not receiving Onpattro in combination with transthyretin stabilizers (e.g., Vyndaqel/Vyndamax).
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 months.12 months

Continuation of Therapy — Amvuttra and Onpattro for hATTR Polyneuropathy

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

Covered when ALL of the following are met:

ALL of the following

Patient has previously received treatment with Amvuttra or Onpattro.
One of continued severity measures
- Patient continues to have a PND score ≤ IIIb.≤ IIIb
- Patient continues to have a FAP stage 1 or 2.Stage 1 or 2
- 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.).
Combination therapy exclusions (drug-specific)
- For Amvuttra
  - Patient is not receiving Amvuttra in combination with other RNA interference agents.
  - Patient is not receiving Amvuttra in combination with transthyretin stabilizers.
- For Onpattro
  - Patient is not receiving Onpattro in combination with other RNA interference agents.
  - Patient is not receiving Onpattro in combination with 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 months.12 months

Provider Actions

Prior Authorization

Prior authorization required for initial and continuation

Initial and continuation prior authorizations are required and are each limited to no more than 12 months. Documentation submitted with requests must demonstrate the diagnosis and one of the following: pathogenic TTR mutation or tissue biopsy confirming ATTR amyloid deposits or imaging criteria (echocardiogram or cardiac MRI suggestive of amyloidosis plus radionuclide imaging with grade 2–3 cardiac uptake and absence of light‑chain amyloidosis). Requests must also document severity/clinical response and that the patient is not receiving excluded combination therapies, and the drug is prescribed by or in consultation with the appropriate specialist (cardiologist for cardiomyopathy; neurologist for polyneuropathy).

Affected HCPCS/J‑codes: J0222, J0225
Specialist requirement: prescribed by or in consultation with cardiologist (for cardiomyopathy) or neurologist (for polyneuropathy)

Documentation Required

Evidence of genetic or histologic confirmation

Provide evidence of genetic or histologic confirmation: documentation of a pathogenic TTR mutation (e.g., V30M), or cardiac or noncardiac tissue biopsy demonstrating histologic ATTR amyloid deposits. Alternatively, provide imaging evidence with echocardiogram or cardiac MRI suggestive of amyloidosis plus radionuclide imaging (99mTc‑DPD, 99mTc‑PYP, or 99mTc‑HMDP) showing grade 2 or 3 cardiac uptake. In all cases, document absence of light‑chain (AL) amyloidosis.

Documentation Required

Clinical severity documentation for polyneuropathy

Document baseline and continued measures of clinical severity for hATTR polyneuropathy: baseline and ongoing PND score (≤ IIIb), FAP Stage (1 or 2), NIS score (≥ 5 and ≤ 130), or KPS score (≥ 60%), plus presence of clinical signs and symptoms (peripheral sensorimotor polyneuropathy, autonomic neuropathy, motor disability, etc.). For initial therapy, document that the patient has not had a liver transplant. Prescriptions should be by or in consultation with a neurologist.

Denial Risk

Combination therapy exclusion

Claims may be denied if the patient is receiving Amvuttra or Onpattro in combination with other RNA interference agents or with transthyretin stabilizers. Ensure the patient is not concurrently treated with listed RNAi agents (for example, Onpattro/patisiran, Wainua/eplontersen, Tegsedi/inotersen) or transthyretin stabilizers (for example, Vyndaqel/Vyndamax) to avoid denial risk.

Affected HCPCS/J‑codes: J0222, J0225

Billing Rule

Drug dosing per FDA label

Drug dosing and administration must follow the U.S. Food and Drug Administration prescribing information. Authorizations for initial therapy and for continuation are each limited to no more than 12 months.

Affected HCPCS/J‑codes: J0222, J0225

Clinical Evidence

HR 0.72HELIOS-B primary endpoint: hazard ratio 0.72 for death and recurrent CV events; p=0.01

26.5 m6-minute walk test LS mean difference at 30 months (vutrisiran vs placebo); p<0.001

-33.99APOLLO mNIS+7 LS mean change at 18 months with patisiran (highly significant)

-17.0Vutrisiran mNIS+7 difference vs external placebo (Month 9); p<0.001

Amvuttra (vutrisiran) and Onpattro (patisiran) are double-stranded small interfering RNAs (siRNAs) that target transthyretin (TTR) mRNA to reduce circulating TTR protein and tissue amyloid deposits by directing RNA degradation in the liver.

FDA-labeled indications differ: Amvuttra is approved for the polyneuropathy of hereditary ATTR and for cardiomyopathy of wild-type or hereditary ATTR; Onpattro is approved for the polyneuropathy of hereditary ATTR.

Key trials supporting clinical benefit include HELIOS-B for vutrisiran (demonstrated lower risk of death and recurrent cardiovascular events and improvements in 6-minute walk distance and KCCQ scores) and APOLLO for patisiran (showed significant improvement in mNIS+7 and quality-of-life measures), as well as vutrisiran hATTR polyneuropathy studies showing mNIS+7 and Norfolk QoL-DN benefits.

Definitions

ATTR-CM: Cardiomyopathy of transthyretin-mediated amyloidosis (wild-type or hereditary).

PND: Polyneuropathy disability score.

FAP: Familial amyloid polyneuropathy staging.

NIS: Neuropathy Impairment Score.

KPS: Karnofsky performance status.

Revision History

06/01/2026revised (non-material)Latest

Archived previous policy versions 2025D0072N and IEXD0072.09.

06/01/2026effectiveLatest

Policy effective date.

06/01/2026reviewedLatest

Policy last reviewed.

Policy Summary

PayerColorado Rocky Mountain Health Plans

PolicyRNA-Targeted Therapies (Amvuttra and Onpattro)

Policy CodePolicy 2026D0072O

Change TypeTemplate update / administrative

Effective DateJun 1, 2026

Next Review Date

On This Page

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

OpenPayer

RNA-Targeted Therapies (Amvuttra and Onpattro)

Coverage Summary

Initial Therapy — Amvuttra for ATTR‑CM

Continuation of Therapy — Amvuttra for ATTR‑CM

Initial Therapy — Amvuttra and Onpattro for hATTR Polyneuropathy

Continuation of Therapy — Amvuttra and Onpattro for hATTR Polyneuropathy

Not Medically Necessary / Unproven

Applicable Codes

Provider Actions

Clinical Evidence

Definitions

Revision History

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