ModifiedUnitedHealthcarePolicy CSLA2025D0072N

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

Louisiana-only UnitedHealthcare medical benefit drug policy defining medical necessity criteria, initial and continuation authorization requirements, exclusions, applicable codes, and prescribing/provider requirements for Amvuttra and Onpattro for treatment of ATTR cardiomyopathy and hATTR polyneuropathy.

Policy Summary

PayerUnitedHealthcare

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

Policy CodePolicy CSLA2025D0072N

Change TypeCoverage criteria expanded; Amvuttra added as medically necessary for ATTR-CM

Effective DateOct 1, 2025

Next Review Date

Key ActionDocument diagnosis, required baseline/continuation measures (PND, FAP, NIS, KPS, NYHA), NT-proBNP for ATTR-CM, and limit authorizations to 12 months as part of prior authorization requests.

POLICY UPDATE CHANGES

Removed language indicating Amvuttra and Onpattro are unproven and not medically necessary for ATTR-CM; added Amvuttra as medically necessary for cardiomyopathy (wtATTR or hATTR) with detailed criteria.

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

Updated Background, Clinical Evidence, FDA, and References sections to reflect current information.

2Indications covered (cardiomyopathy, polyneuropathy)

12 monthsAuthorization duration (initial/continuation)

4Key baseline eligibility thresholds listed

Coverage Summary

Louisiana-only UnitedHealthcare medical benefit drug policy (Policy Number CSLA2025D0072N, Effective/Last Review 2025-10-01) covering Amvuttra (vutrisiran) and Onpattro (patisiran) for transthyretin (ATTR) cardiomyopathy and hereditary ATTR polyneuropathy. Coverage stance is mixed with both initial and continuation medical necessity criteria defined for: Amvuttra for ATTR-CM (wtATTR or hATTR) and Amvuttra or Onpattro for polyneuropathy of hATTR. Authorizations (initial and continuation) are limited to no more than 12 months. Detailed initial and continuation criteria exist for each indication (diagnosis, diagnostic confirmation, functional class/score thresholds, combination therapy exclusions, prescribing specialty, and dosing per FDA), but full criteria are not reproduced here.

Key thresholds & quick facts

NYHA classI, II, or III

PND score threshold≤ IIIb

FAP stageStage 1 or 2

NIS range≥ 5 and ≤ 130

Karnofsky performance status (KPS)≥ 60%

Radionuclide cardiac uptakeGrade 2 or 3

Authorization durationInitial/continuation authorization: up to 12 months

Indications covered2 (cardiomyopathy and polyneuropathy)

Amvuttra for Cardiomyopathy — Initial Therapy (medically necessary)

Amvuttra for Cardiomyopathy — Continuation of Therapy (medically necessary)

Amvuttra and Onpattro for Polyneuropathy of hATTR — Initial Therapy (medically necessary)

Amvuttra and Onpattro for Polyneuropathy of hATTR — Continuation of Therapy (medically necessary)

Unproven / Not Medically Necessary

Applicable Codes

Drug HCPCS / J-codesHCPCS

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

ICD-10 Diagnoses (applicable)ICD-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 Impact

Prior Authorization

Prior authorization required / authorization duration

Initial and continuation authorizations are limited to no more than 12 months. Radionuclide imaging (99mTc-DPD, 99mTc-PYP, or 99mTc-HMDP) with grade 2 or 3 cardiac uptake may require prior authorization and notification. Affected codes: J0222, J0225.

Authorization duration: initial and continuation — up to 12 months
Radionuclide imaging (99mTc‑DPD, 99mTc‑PYP, 99mTc‑HMDP) grade 2–3 uptake may require prior authorization/notification
Affected HCPCS / J-codes: J0222, J0225

Documentation Required

Clinical documentation required

Providers must document diagnosis and confirmatory evidence, baseline and/or continuing disease measures, cardiac-specific measures for ATTR-CM, prior hospitalizations or signs/symptoms of heart failure, and evidence of a positive clinical response for continuation.

Clinical Evidence

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

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

-17.0Vutrisiran mNIS+7 difference vs external placebo at Month 9; 95% CI -21.8 to -12.2; p<0.001

Key clinical evidence summarized in the policy: the phase 3 HELIOS-B trial supports a clinical benefit for vutrisiran in ATTR cardiomyopathy (reduced risk of death and recurrent cardiovascular events), while the APOLLO phase 3 trial supports patisiran benefit for hATTR polyneuropathy (significant improvement in mNIS+7 at 18 months). The policy notes safety signals observed in trials, including decreases in vitamin A levels and infusion-/injection-related reactions. The supporting information and references were refreshed in the current policy revision.

Background

Amvuttra (vutrisiran) and Onpattro (patisiran) are transthyretin-directed double-stranded small interfering RNAs (siRNAs) formulated to target TTR mRNA across wild-type and variant TTR sequences, reduce serum TTR levels, and decrease tissue amyloid deposits; they are directed to the liver as the primary source of circulating TTR. Common/measured safety signals in trials include decreased vitamin A (with vitamin A supplementation recommended) and infusion- or injection-related reactions.

Definitions

ATTR-CM (term)Transthyretin-mediated amyloidosis with cardiomyopathy

PND score (definition)Polyneuropathy disability score used to stage neuropathy severity

NIS (definition)Neuropathy Impairment Score — measure of neuropathic impairment

Revision History

2025-10-01material_changeLatest

Removed prior language that Amvuttra (vutrisiran) and Onpattro (patisiran) were unproven and not medically necessary for ATTR-CM; added Amvuttra as medically necessary for treatment of cardiomyopathy of wild-type (wtATTR) or hereditary transthyretin-mediated (hATTR) amyloidosis with detailed initial and continuation criteria (diagnosis, biopsy or imaging/NT-proBNP/NYHA requirements, absence of AL amyloidosis, prior therapy intolerance pathways) and specified initial and continuation authorizations limited to no more than 12 months.

2025-10-01non_material_change

Applicable ICD-10 diagnosis codes E85.0, E85.4, and E85.82 were added to the policy's applicable codes list.

Policy Summary

PayerUnitedHealthcare

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

Policy CodePolicy CSLA2025D0072N

Change TypeCoverage criteria expanded; Amvuttra added as medically necessary for ATTR-CM

Effective DateOct 1, 2025

Next Review Date

Key ActionDocument diagnosis, required baseline/continuation measures (PND, FAP, NIS, KPS, NYHA), NT-proBNP for ATTR-CM, and limit authorizations to 12 months as part of prior authorization requests.

On This Page

Diagnosis of wtATTR or hATTR (cardiomyopathy) or hATTR with polyneuropathy
Pathogenic TTR mutation (e.g., V30M) OR cardiac/noncardiac biopsy showing ATTR deposits OR imaging consistent with amyloidosis (echo or cardiac MRI, radionuclide imaging grade 2–3) and absence of AL amyloidosis
Baseline/continuation measures: PND, FAP stage, NIS, Karnofsky Performance Status (KPS)
For cardiomyopathy: NYHA class I–III and physician attestation of NT‑proBNP combined with signs/symptoms as definitive
History of heart failure with at least one prior hospitalization OR presence of signs/symptoms (e.g., dyspnea, edema)
For continuation: documentation of positive clinical response (improved symptoms, QoL, slowed progression, fewer hospitalizations)

Billing Rule

Prescribing specialty requirement

Prescriptions must be by or in consultation with the appropriate specialist: cardiologist for cardiomyopathy indications; neurologist for polyneuropathy indications.

Cardiomyopathy (ATTR‑CM) — prescribed by or in consultation with a cardiologist
Polyneuropathy of hATTR — prescribed by or in consultation with a neurologist

Denial Risk

Combination therapy exclusion

Claims may be denied if Amvuttra (vutrisiran) or Onpattro (patisiran) are administered concomitantly with other RNA interference agents or transthyretin stabilizers as specified in the policy. Affected codes: J0222, J0225.

Combination exclusion: no concomitant RNAi agents (e.g., patisiran, eplontersen, inotersen)
Combination exclusion: no concomitant transthyretin stabilizers (e.g., tafamidis products)
Affected HCPCS / J-codes: J0222, J0225

Documentation Required

NT-proBNP attestation

For the cardiomyopathy indication, the physician must attest that the NT-proBNP level, when combined with signs and symptoms, is considered definitive for a diagnosis of ATTR-CM.

NT-proBNP attestation required: level + signs/symptoms considered definitive for ATTR‑CM diagnosis

Supporting information sections (Background, Clinical Evidence, FDA, and References) were updated and the previous policy version CSLA2024D0072M was archived.

2025-10-01administrative

Policy effective date set to October 1, 2025 and policy number CSLA2025D0072N recorded for Louisiana-only medical benefit drug policy.