CurrentColorado Rocky Mountain Health PlansPolicy CS2026D0072S

RNA-Targeted Therapies (Amvuttra and Onpattro)

Medical benefit drug policy describing clinical coverage criteria, initial and continuation authorization requirements, exclusions, and applicable procedure/diagnosis codes for Amvuttra (vutrisiran) and Onpattro (patisiran) for treatment of ATTR cardiomyopathy and hATTR polyneuropathy; applies to most states except several noted.

Policy Summary

PayerColorado Rocky Mountain Health Plans

PolicyRNA-Targeted Therapies (Amvuttra and Onpattro)

Policy CodePolicy CS2026D0072S

Change TypeSupporting information / References updated

Effective DateJun 1, 2026

Next Review Date

Key ActionProviders must document diagnosis, mutation/biopsy/imaging criteria, severity scores (NYHA or PND/FAP/NIS/KPS), prior therapies or intolerance, and evidence of clinical response for continuation requests.

SourceLink

POLICY UPDATE CHANGES

06/01/2026 summary of changes indicates reference/supporting information updates only.

2Indications covered (cardiomyopathy; polyneuropathy)

12Max initial authorization (months)

J0222, J0225Key HCPCS codes

Coverage Summary

Policy CS2026D0072S (effective June 1, 2026; last reviewed June 1, 2026) covers RNA-targeted therapies Amvuttra (vutrisiran) and Onpattro (patisiran) under a covered_with_criteria stance. Indications covered include ATTR cardiomyopathy (wtATTR or hATTR) and hATTR polyneuropathy. The policy is a medical benefit drug policy that defines clinical coverage criteria for initial and continuation therapy, specialist prescribing requirements, combination-therapy exclusions, applicable HCPCS and ICD-10 codes, and limits such as initial authorizations up to 12 months.

Key thresholds

NYHA classI, II, or III required for ATTR-CM

Radionuclide imaging uptakeGrade 2 or 3 cardiac uptake (99mTc-DPD, 99mTc-PYP, or 99mTc-HMDP)

PND scoreBaseline PND ≤ IIIb for hATTR polyneuropathy

FAP stageBaseline FAP Stage 1 or 2 for hATTR polyneuropathy

NISBaseline NIS ≥ 5 and ≤ 130 for hATTR polyneuropathy

KPSBaseline Karnofsky Performance Status ≥ 60% for hATTR polyneuropathy

Max initial authorization durationInitial authorization is for no more than 12 months

Amvuttra for ATTR cardiomyopathy — Initial Therapy

Prior Authorization

Prior authorization required / initial authorization duration

Initial authorization required; initial approvals are limited to no more than 12 months. Prior authorization and notification may be required when radionuclide imaging (99mTc-DPD, 99mTc-PYP, or 99mTc-HMDP) showing grade 2 or 3 cardiac uptake is used to document ATTR-CM.

Initial authorization no more than 12 months
Radionuclide imaging may require prior authorization/notification

Amvuttra for ATTR cardiomyopathy — Continuation Therapy

Documentation Required

Specialist prescribing requirement — cardiology

For cardiomyopathy (ATTR-CM) therapies, the drug must be prescribed by or in consultation with a cardiologist; include cardiology involvement in the medical record for initial and continuation requests.

Amvuttra and Onpattro for hATTR polyneuropathy — Initial Therapy

Documentation Required

Required diagnostic and severity documentation

Providers must document: diagnosis (ATTR-CM or hATTR polyneuropathy); evidence of a pathogenic TTR mutation or confirmatory tissue biopsy or appropriate cardiac imaging (echocardiogram/CMR) and, if used, radionuclide imaging criteria; baseline and ongoing severity/performance measures (NYHA class for cardiomyopathy; PND, FAP stage, NIS, KPS for polyneuropathy); NT‑proBNP for ATTR‑CM; prior therapies or intolerance (e.g., tafamidis, acoramidis) and rationale; and evidence of positive clinical response for continuation requests.

Diagnosis (ATTR‑CM or hATTR polyneuropathy)
TTR mutation or biopsy/imaging (echo/CMR; radionuclide grade 2–3 when applicable)
Severity/performance: NYHA (cardiomyopathy); PND, FAP stage, NIS, KPS (polyneuropathy)
NT‑proBNP for cardiomyopathy
Prior therapies or intolerance (e.g., tafamidis, acoramidis)
Evidence of clinical response for continuation

Amvuttra and Onpattro for hATTR polyneuropathy — Continuation Therapy

Documentation Required

Specialist prescribing requirement — neurology

For hATTR polyneuropathy therapies (Amvuttra or Onpattro), the drug must be prescribed by or in consultation with a neurologist; include neurology involvement in the medical record for initial and continuation requests.

Not Medically Necessary / Exclusions

Billing Rule

Combination therapy exclusion — potential claim denial

Claims may be denied if Amvuttra (J0225) or Onpattro (J0222) are used in combination with other listed RNA interference agents or transthyretin stabilizers; the policy excludes combination use and denial may follow per the product-specific exclusions.

Affected codes: J0222, J0225

Provider Actions

Prior Authorization

Prior authorization required / initial authorization duration (codes)

Prior authorization is required for these therapies. Initial authorizations are limited to no more than 12 months. Applicable HCPCS drug codes include J0222 (patisiran) and J0225 (vutrisiran). Prior authorization/notification may be required when radionuclide imaging is used to document cardiac uptake.

Affected codes: J0222, J0225
Initial authorization limit: 12 months
Radionuclide imaging may require prior authorization/notification

Documentation Required

Required diagnostic and severity documentation (initial and continuation)

Required documentation for initial and continuation requests includes diagnosis (ATTR‑CM or hATTR polyneuropathy); TTR mutation or biopsy/imaging confirmation; baseline and follow‑up severity/performance measures (NYHA for ATTR‑CM; PND, FAP stage, NIS, KPS for polyneuropathy); NT‑proBNP for cardiomyopathy; documentation of prior therapies or intolerance; and documentation of clinical response for continuation.

Documentation Required

Specialist prescribing requirement — cardiology and neurology

Specialist prescribing requirements: Amvuttra for ATTR‑CM must be prescribed by or in consultation with a cardiologist. Therapies for hATTR polyneuropathy (Amvuttra or Onpattro) must be prescribed by or in consultation with a neurologist.

Cardiology involvement required for Amvuttra — ATTR‑CM
Neurology involvement required for Amvuttra/Onpattro — hATTR polyneuropathy

Billing Rule

Combination therapy exclusion / denial risk

The policy excludes combination use of these agents. Claims may be denied if Amvuttra or Onpattro are used in combination with other RNA interference agents or transthyretin stabilizers as specified in the product‑specific combination exclusions in the policy.

Use in combination with excluded agents may result in denial

Clinical Evidence

0.72HELIOS-B primary outcome HR for death and recurrent CV events (95% CI 0.56–0.93; p=0.01)

-33.99APOLLO mNIS+7 LS mean change at 18 months (Patisiran -6.03; placebo +27.96)

-17.0Vutrisiran mNIS+7 difference vs external placebo at 9 months (95% CI -21.8, -12.2; p<0.001)

Background: Amvuttra (vutrisiran) and Onpattro (patisiran) are transthyretin-directed small interfering RNAs indicated for the polyneuropathy of hereditary transthyretin-mediated (hATTR) amyloidosis; Amvuttra is additionally indicated for cardiomyopathy of wild-type or hereditary transthyretin-mediated (ATTR-CM). The policy summarizes pivotal trial evidence: HELIOS‑B (phase 3 randomized study of vutrisiran in ATTR‑CM) demonstrated a lower risk of death and recurrent cardiovascular events (hazard ratio 0.72, 95% CI 0.56–0.93; p=0.01) and secondary functional and quality-of-life benefits, while APOLLO (phase 3 randomized, placebo-controlled study of patisiran in hATTR polyneuropathy) showed large, highly significant improvement in mNIS+7 (LS mean change -33.99; patisiran -6.03 vs placebo +27.96) and multiple secondary endpoints with acceptable safety. The policy was updated on 06/01/2026 for supporting information and references (summary of changes indicates reference/supporting information updates only).

Definitions

Glossary:

ATTR-CM: Transthyretin-mediated amyloidosis with cardiomyopathy (cardiac involvement of ATTR amyloid).

hATTR: Hereditary transthyretin-mediated amyloidosis (TTR gene variant–associated disease).

PND score: Polyneuropathy disability score (used to stage functional impairment in hATTR polyneuropathy; policy requires ≤ IIIb for initiation/continuation).

NIS: Neuropathy Impairment Score (neurologic impairment scale; policy thresholds use ≥ 5 and ≤ 130).

Revision History

06/01/2026revisedLatest

Summary of changes indicates reference/supporting information updates only. Supporting Information updated and References section updated to reflect the most current information; previous policy version CS2026D0072R archived.

Policy Summary

PayerColorado Rocky Mountain Health Plans

PolicyRNA-Targeted Therapies (Amvuttra and Onpattro)

Policy CodePolicy CS2026D0072S

Change TypeSupporting information / References updated

Effective DateJun 1, 2026

Next Review Date

SourceLink

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

Amvuttra for ATTR cardiomyopathy — Initial Therapy

Amvuttra for ATTR cardiomyopathy — Continuation Therapy

Amvuttra and Onpattro for hATTR polyneuropathy — Initial Therapy

Amvuttra and Onpattro for hATTR polyneuropathy — Continuation Therapy

Not Medically Necessary / Exclusions

Applicable Codes

Provider Actions

Clinical Evidence

Definitions

Revision History