CurrentColorado Rocky Mountain Health PlansPolicy CS2026D0072S

Rna Targeted Therapies Cs

Defines medical necessity criteria, initial and continuation authorization rules, exclusions, and applicable billing codes for Amvuttra (vutrisiran) and Onpattro (patisiran) for treatment of cardiomyopathy and polyneuropathy related to transthyretin-mediated (ATTR) amyloidosis. Applies to commercial Medical Benefit drug coverage except where state-specific guidance supersedes.

Policy Summary

PayerColorado Rocky Mountain Health Plans

PolicyRna Targeted Therapies Cs

Policy CodePolicy CS2026D0072S

Change TypeRevised references

Effective DateJun 1, 2026

Next Review Date

Key ActionDocument that all coverage criteria are met for initial and continuation authorization; initial and continuation authorizations limited to no more than 12 months.

SourceLink

POLICY UPDATE CHANGES

Updated References section to reflect the most current information; archived previous policy version CS2026D0072R.

2Agents covered (Amvuttra, Onpattro)

2Indications addressed (cardiomyopathy, polyneuropathy)

2Excluded uses listed

12Maximum authorization duration (months)

Coverage Summary

Policy Number: CS2026D0072S. Effective/Last review date: June 1, 2026. Status: CURRENT.

Scope: Defines medical necessity criteria, initial and continuation authorization rules, exclusions, and applicable billing codes for Amvuttra (vutrisiran) and Onpattro (patisiran) for treatment of cardiomyopathy and polyneuropathy related to transthyretin-mediated (ATTR) amyloidosis; applies to commercial Medical Benefit drug coverage except where state-specific guidance supersedes.

Coverage stance: mixed — the policy includes both covered indications with specific criteria and explicit exclusions for non-ATTR uses.

Agents covered: Amvuttra (vutrisiran) and Onpattro (patisiran) (HCPCS J0225 and J0222 referenced).

Indications addressed: Polyneuropathy of hereditary ATTR (hATTR) (both agents) and cardiomyopathy of wild-type or hereditary ATTR (ATTR-CM) (Amvuttra).

Authorization durations (high-level): Initial and continuation authorizations limited to no more than 12 months with prior authorization and documentation requirements.

Cardiomyopathy — Initial Therapy (Amvuttra)

Cardiomyopathy of Wild-Type (wtATTR) or Hereditary (hATTR) ATTR amyloidosis — Amvuttra (vutrisiran)

Covered 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 imaging/biomarker pathway
  - 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

Cardiomyopathy — Continuation of Therapy (Amvuttra)

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)
Documentation that the patient continues to have NYHA Functional Class I, II, or III heart failureNYHA I-III
Patient is not receiving Amvuttra in combination with RNA interference agents or transthyretin stabilizers

Polyneuropathy — Initial Therapy (Amvuttra or Onpattro)

Polyneuropathy of Hereditary ATTR (hATTR) — Initial Therapy (Amvuttra or Onpattro)

Covered when ALL of the following are met:

ALL of the following

Required baseline diagnostic criteria
- Diagnosis of hATTR amyloidosis with polyneuropathy
- Documentation that the patient has a pathogenic TTR mutation (e.g., V30M)
One of the following baseline severity/performance measures
- Baseline polyneuropathy disability (PND) score ≤ IIIb≤ IIIb

Polyneuropathy — Continuation of Therapy (Amvuttra or Onpattro)

Covered when ALL of the following are met:

ALL of the following

Patient has previously received treatment with Amvuttra or Onpattro
Continuation disease severity/performance criteria (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 / Exclusions

Not covered when the following diagnoses or uses apply:

ANY of the following

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

Applicable Codes

HCPCS J-codes for agents referencedHCPCS

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

ICD-10 diagnosis codes referencedICD-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 & Billing Rules

Prior Authorization

Prior authorization required for Amvuttra/Onpattro

Prior authorization is required for Amvuttra (vutrisiran) and Onpattro (patisiran). Initial and continuation authorizations are limited to no more than 12 months and require documentation that all coverage criteria are met.

J0222
J0225

Documentation Required

Diagnostic and severity documentation

Document diagnostic confirmation and baseline disease severity to support medical necessity. Required elements include evidence of a pathogenic TTR mutation or tissue biopsy/imaging confirmation of ATTR amyloid deposits; baseline measures for polyneuropathy (PND, FAP stage, NIS, KPS); and for cardiomyopathy, NYHA functional class and an NT‑proBNP level documented as definitive when combined with signs/symptoms.

Clinical Evidence

0.72 (95% CI 0.56-0.93)HELIOS-B primary endpoint hazard ratio for death and recurrent CV events (vutrisiran vs placebo)

LS mean change -33.99APOLLO mNIS+7 change at 18 months favoring patisiran (p=9.26x10^-24)

Difference -17.0Vutrisiran effect on mNIS+7 vs external placebo (95% CI -21.8 to -12.2); p<0.001

Key trial evidence summarized in the policy includes the phase 3 HELIOS-B trial for vutrisiran and the phase 3 APOLLO trial for patisiran; the policy also summarizes safety data for both agents.

HELIOS-B (vutrisiran) is cited for ATTR-CM efficacy and safety; APOLLO (patisiran) is cited for hATTR polyneuropathy efficacy and safety.

Safety summaries referenced in the policy include adverse event profiles and trial safety conclusions (e.g., infusion- or injection-related reactions, vitamin A changes, and overall tolerability) for the respective agents.

Background

Background: Amvuttra (vutrisiran) and Onpattro (patisiran) are transthyretin-directed small interfering RNAs (siRNAs) that reduce circulating TTR by targeting conserved TTR mRNA sequences and are directed to the liver via lipid formulations.

Indications: Both agents are indicated for the polyneuropathy of hereditary transthyretin-mediated (hATTR) amyloidosis; Amvuttra (vutrisiran) is additionally indicated for cardiomyopathy of wild-type or hereditary ATTR (ATTR-CM) to reduce cardiovascular mortality and cardiovascular hospitalizations/urgent heart failure visits.

Trial context: The policy references HELIOS-B, a phase 3 randomized double-blind study establishing vutrisiran benefit on a composite primary endpoint of death and recurrent cardiovascular events in ATTR-CM, and APOLLO, a randomized phase 3 placebo-controlled study demonstrating significant improvement in modified NIS+7 and other endpoints with patisiran in hATTR polyneuropathy. The policy also cites an open-label vutrisiran polyneuropathy study compared with an external placebo.

Safety reference: The policy summarizes safety findings from the trials, including reported adverse reactions (e.g., infusion/injection–site reactions, changes in vitamin A, and cardiac conduction events) and investigators’ overall safety conclusions.

Revision History

2026-06-01policy_revisionLatest

Summary of Changes dated 06/01/2026 indicates supporting information and references updated; no clinical policy statement changes noted. Updated References section; archived previous policy version CS2026D0072R.

Policy Summary

PayerColorado Rocky Mountain Health Plans

PolicyRna Targeted Therapies Cs

Policy CodePolicy CS2026D0072S

Change TypeRevised references

Effective DateJun 1, 2026

Next Review Date

Key ActionDocument that all coverage criteria are met for initial and continuation authorization; initial and continuation authorizations limited to no more than 12 months.

SourceLink

On This Page

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 NT-proBNP level that, when combined with signs and symptoms, is considered definitive for a diagnosis of ATTR-CM

Commercial policy additional clinical context (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)

One of the following for progressive disease or intolerance

Documentation of progressive worsening or an event resulting in hospitalization related to hATTR-mediated amyloidosis with cardiomyopathy while on Vyndaqel (tafamidis meglumine) or Vyndamax (tafamidis)
Documentation of progressive worsening or an event resulting in hospitalization related to hATTR-mediated amyloidosis with cardiomyopathy while on Attruby (acoramidis)
Documentation of intolerance or contraindication to both tafamidis (Vyndaqel/Vyndamax) AND acoramidis (Attruby)

Patient is not receiving Amvuttra in combination with any RNA interference agents (e.g., Onpattro/patisiran, Wainua/eplontersen, Tegsedi/inotersen) or transthyretin stabilizers (e.g., tafamidis)

Prescribed by or in consultation with a cardiologist

Dosing is in accordance with FDA prescribing information

Initial authorization duration: no more than 12 months12 months

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title": "Cardiomyopathy of Wild-Type (wtATTR) or Hereditary (hATTR) ATTR amyloidosis — Amvuttra (vutrisiran)"

Prescribed by or in consultation with a cardiologist

Dosing is in accordance with FDA prescribing information

Authorization duration: no more than 12 months12 months

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title": "Cardiomyopathy — Continuation of Therapy (Amvuttra)"

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)

Patient has not had a liver transplant

Agent-specific combination exclusion (one of)

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

Prescribed by or in consultation with a neurologist

Dosing is in accordance with FDA prescribing information

Initial authorization duration: no more than 12 months12 months

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title": "Polyneuropathy of Hereditary ATTR (hATTR) — Initial Therapy (Amvuttra or Onpattro)"

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)

Agent-specific combination exclusion (one of)

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 or transthyretin stabilizers

Prescribed by or in consultation with a neurologist

Dosing is in accordance with FDA prescribing information

Authorization duration: no more than 12 months12 months

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title": "Polyneuropathy — Continuation of Therapy (Amvuttra or Onpattro)"

Pathogenic TTR mutation OR cardiac/noncardiac tissue biopsy demonstrating ATTR deposits OR echocardiogram/CMR or radionuclide imaging showing grade 2–3 cardiac uptake
Baseline PND, FAP stage, NIS, or KPS for polyneuropathy
NYHA class and NT-proBNP for cardiomyopathy

Denial Risk

Combination therapy exclusion

Claims may be denied if Amvuttra (J0225) or Onpattro (J0222) are administered in combination with other RNA interference agents or with transthyretin stabilizers; the policy explicitly excludes concurrent use and notes that patients must not be receiving these combinations.

J0222
J0225

Documentation Required

Specialty prescriber requirement

Prescriber specialty must be documented. Amvuttra for cardiomyopathy must be prescribed by or in consultation with a cardiologist; Amvuttra or Onpattro for polyneuropathy must be prescribed by or in consultation with a neurologist.

Billing Rule

Dosing per FDA labeling

Dosing and administration must follow the FDA prescribing information. Note that administration routes differ: Amvuttra is given subcutaneously and Onpattro is given intravenously; billing should use the applicable HCPCS codes.

J0222
J0225