Modifiedsierra health and lifePolicy 2025D0072N

RNA-Targeted Therapies (Amvuttra and Onpattro) — Coverage Criteria for ATTR amyloidosis

Defines medical necessity criteria, prior authorization, and coverage rationale for Amvuttra (vutrisiran) and Onpattro (patisiran) for cardiomyopathy and polyneuropathy related to transthyretin-mediated (ATTR) amyloidosis for Sierra Health and Life members.

Policy Summary

Payersierra health and life

PolicyRNA-Targeted Therapies (Amvuttra and Onpattro) — Coverage Criteria for ATTR amyloidosis

Policy CodePolicy 2025D0072N

Change TypeCriteria added and coverage stance revised (material)

Effective DateJun 1, 2025

Next Review DateN/A

Key ActionObtain prior authorization with documentation of diagnostic confirmation of ATTR-CM, NYHA class I–III, prior therapy status or intolerance, and ensure prescriber is or consults with a cardiologist; limit authorization requests to ≤12 months and follow FDA dosing.

SourceLink

POLICY UPDATE CHANGES

Removed language indicating Amvuttra (vutrisiran) and Onpattro (patisiran) are unproven and not medically necessary for the treatment of transthyretin (ATTR)-mediated amyloidosis with cardiomyopathy (ATTR-CM).

Added coverage criteria indicating Amvuttra (vutrisiran) is medically necessary for treatment of wtATTR or hATTR amyloidosis with cardiomyopathy when specific diagnostic, functional, and prior-therapy conditions are met.

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

Authorization periods and dosing are aligned with U.S. FDA prescribing information and initial/continuation authorizations are for no more than 12 months.

Supporting information sections updated and a CMS section was added.

655HELIOS-B randomized

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

Coverage Criteria and Clinical Evidence

Amvuttra for ATTR cardiomyopathy — Initial Therapy

Covered when ALL of the following are met

Initial therapy criteria: Diagnosis of wild-type or hereditary ATTR-mediated amyloidosis with cardiomyopathy (ATTR-CM); and documentation of one of the following: pathogenic TTR mutation (e.g., V30M), OR cardiac or noncardiac tissue biopsy demonstrating histologic confirmation of ATTR amyloid deposits, OR ALL of: echocardiogram or cardiac MRI suggestive of amyloidosis AND radionuclide imaging (99mTc-DPD, 99mTc-PYP, or 99mTc-HMDP) showing grade 2 or 3 cardiac uptake AND absence of light-chain (AL) amyloidosis; and patient is not receiving Amvuttra in combination with RNA interference agents (e.g., patisiran, eplontersen, inotersen) or transthyretin stabilizers (e.g., tafamidis); and prescribed by or in consultation with a cardiologist; and dosing is in accordance with U.S. FDA prescribing information; and initial authorization is for no more than 12 months.

From Initial Therapy section

Amvuttra for ATTR cardiomyopathy — Continuation Therapy

Covered when ALL of the following are met

Continuation therapy criteria: Patient has previously received treatment with Amvuttra for wtATTR or hATTR cardiomyopathy; and documentation the patient has experienced a positive clinical response to Amvuttra (e.g., improved symptoms, quality of life, slowed progression, decreased hospitalizations); and documentation that the patient continues to have NYHA Functional Class I, II, or III heart failure; and patient is not receiving Amvuttra in combination with RNA interference agents or transthyretin stabilizers; and prescribed by or in consultation with a cardiologist; and dosing is in accordance with U.S. FDA prescribing information; and authorization is for no more than 12 months.NYHA I-III

From Continuation of Therapy section

Amvuttra or Onpattro for hATTR polyneuropathy — Initial and Continuation

Covered when ALL of the following are met

Initial therapy (hATTR polyneuropathy): Diagnosis of hereditary (hATTR) transthyretin-mediated amyloidosis with polyneuropathy; and documentation of a pathogenic TTR mutation (e.g., V30M); and documentation of one of: baseline PND score ≤ IIIb, OR baseline FAP Stage 1 or 2, OR baseline NIS ≥ 5 and ≤ 130, OR baseline KPS ≥ 60%; and presence of clinical signs and symptoms of polyneuropathy (e.g., peripheral sensorimotor or autonomic neuropathy, motor disability); and patient has not had a liver transplant; and for Amvuttra (vutrisiran) the patient is not receiving it in combination with other RNA interference agents or transthyretin stabilizers (and analogous combination exclusions apply for Onpattro); and prescribed by or in consultation with a neurologist; and dosing is in accordance with U.S. FDA prescribing information; and initial authorization is for no more than 12 months.PND ≤ IIIb; FAP 1–2; NIS 5–130; KPS ≥ 60%

From Initial Therapy (polyneuropathy)

Continuation therapy (hATTR polyneuropathy): Patient has previously received treatment with Amvuttra or Onpattro; and documentation that the patient continues to meet one of the disease-severity thresholds (PND ≤ IIIb, FAP Stage 1–2, NIS 5–130, or KPS ≥ 60%); and documentation of a positive clinical response; and patient is not receiving prohibited combination therapies; and prescribed by or in consultation with a neurologist; and dosing is in accordance with U.S. FDA prescribing information; and authorization is for no more than 12 months.

Initial Therapy (Amvuttra for ATTR-CM)

Covered when ALL of the following are met:

Diagnostic confirmation: Diagnosis of wild-type or hereditary ATTR-mediated amyloidosis with cardiomyopathy documented by one of: pathogenic TTR mutation; cardiac or noncardiac tissue biopsy with histologic confirmation of ATTR deposits; echocardiogram or cardiac MRI suggestive of amyloidosis; OR radionuclide imaging (99mTc-DPD, 99mTc-PYP, or 99mTc-HMDP) showing grade 2 or 3 cardiac uptake (may require prior authorization/notification).

From Initial Therapy (Amvuttra for ATTR-CM)

Exclude light-chain amyloidosis: Absence of light-chain (AL) amyloidosis must be documented.

Functional class and biomarkers: Patient has NYHA Functional Class I, II, or III heart failure and physician attests that NT-proBNP level combined with signs/symptoms is considered definitive for ATTR-CM.NYHA I-III

Continuation of Therapy (Amvuttra)

Covered when ALL of the following are met:

Prior treatment: Patient has previously received Amvuttra for treatment of wtATTR or hATTR amyloidosis.

Clinical response: 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).

NYHA class: Patient continues to have NYHA Functional Class I, II, or III heart failure.NYHA I-III

Therapy combination exclusion continued: Patient is not receiving Amvuttra in combination with other RNA interference agents or transthyretin stabilizers.

Clinical evidence summary (informational)

Evidence supporting clinical benefit from trials:

HELIOS-B cardiomyopathy outcomes: HELIOS-B: vutrisiran (25 mg q12w) reduced the risk of death from any cause and recurrent cardiovascular events versus placebo (HR 0.72; 95% CI 0.56–0.93; p=0.01) with secondary mortality benefit through 42 months and improvements in 6-minute walk distance and KCCQ-OS; trial enrolled patients with ATTR cardiomyopathy.

From HELIOS-B summary and FDA section

APOLLO polyneuropathy outcomes: APOLLO: patisiran improved modified NIS+7 at 18 months (LS mean change -33.99), Norfolk QoL-DN, and multiple secondary endpoints; cardiac subpopulation showed improvements in GLS, reductions in LV wall thickness, and decreased NT-proBNP.

From APOLLO trial summaries

Vutrisiran polyneuropathy study outcomes: Vutrisiran (vutrisiran) polyneuropathy studies showed significant benefit versus external placebo on mNIS+7, Norfolk QoL-DN, 10-meter walk test, and mBMI at 9 months; common adverse reactions included arthralgia, dyspnea, and decreased vitamin A; rare serious events included AV heart block.

From vutrisiran polyneuropathy trials

Initial and Continuation Authorization Criteria

Coverage requires the following elements for initial or continuation authorization:

Prescriber and dosing: Prescribed by or in consultation with a cardiologist AND dosing is in accordance with U.S. FDA prescribing information.

Supports both initial and continuation authorization

Authorization duration: Initial and continuation authorizations are limited to no more than 12 months.<=12 months

Renewal requires reauthorization

Prior therapy/combo restrictions: Patient is not receiving Amvuttra in combination with RNA interference agents (e.g., patisiran, eplontersen, inotersen) OR documentation of intolerance or contraindication to transthyretin stabilizers (tafamidis or acoramidis) when applicable.

Step therapy or combination restriction described

Amvuttra (vutrisiran) and Onpattro (patisiran) are considered unproven and not medically necessary when used for the treatment of sensorimotor or autonomic neuropathy not related to hereditary transthyretin-mediated (hATTR) amyloidosis and for primary or leptomeningeal amyloidosis.

Amvuttra must not be prescribed concurrently with other RNA interference agents (for example, Onpattro/patisiran, Wainua/eplontersen, or inotersen) or with transthyretin stabilizers (for example, Vyndaqel/Vyndamax [tafamidis] or Attruby [acoramidis]). Documentation supporting prior therapy, intolerance, or contraindication to stabilizers may be required per the coverage criteria.

Use of Amvuttra in combination with any RNA interference agents (eg, patisiran, eplontersen, inotersen) or with transthyretin stabilizers (eg, tafamidis) is explicitly prohibited and may result in denial of the authorization request.

Vutrisiran (Amvuttra) and patisiran (Onpattro) are authorized only for indications supported by the policy criteria. For polyneuropathy due to hATTR, coverage requires a documented pathogenic TTR mutation and baseline disease severity that meets one of the listed thresholds (for example, PND score ≤ IIIb; FAP Stage 1–2; NIS 5–130; or KPS ≥ 60%), clinician documentation of signs and symptoms, and adherence to dosing and prescriber specialty requirements. Use of these agents for neuropathies not related to hATTR is not medically necessary.

Previous language that characterized Amvuttra and Onpattro as unproven and not medically necessary for ATTR cardiomyopathy was removed. The policy now states that Amvuttra (vutrisiran) is proven and may be medically necessary for treatment of wild-type or hereditary ATTR amyloidosis with cardiomyopathy when all coverage criteria are met (diagnostic confirmation, NYHA class I–III, prior therapy or intolerance documentation when applicable, prescriber and dosing requirements, and authorization limits).

Within the cited policy fragments there are no additional explicit statements declaring vutrisiran or patisiran as not medically necessary; the document focuses on permitted indications and specific coverage criteria rather than repeating prior NMN language.

Prior Authorization, Documentation, and Prescriber Requirements

Prior Authorization

Prior authorization required

Prior authorization is required for Amvuttra (vutrisiran). Initial authorization is limited to no more than 12 months and dosing must follow the U.S. Food and Drug Administration prescribing information. Prescriptions must be written by or in consultation with a cardiologist for ATTR-CM indications (or a neurologist for polyneuropathy indications).

Initial authorization ≤ 12 months
Dosing per FDA prescribing information
Prescribed by or in consultation with a cardiologist (cardiomyopathy) or neurologist (polyneuropathy)

Documentation Required

Required diagnostic and neuropathy documentation

Documentation must confirm the diagnosis and exclude light-chain (AL) amyloidosis. For ATTR-CM (wild-type or hereditary) include diagnostic evidence: pathogenic TTR mutation, biopsy confirmation, or imaging (echocardiogram or cardiac MRI suggestive of amyloidosis AND radionuclide imaging with 99mTc-DPD, 99mTc-PYP, or 99mTc-HMDP showing grade 2 or 3 cardiac uptake). For hATTR with polyneuropathy, document a pathogenic TTR mutation and baseline disease severity metrics and clinical signs/symptoms.

Applicable Codes and Clinical Thresholds

Applicable codesmixed

J0222	Injection, patisiran, 0.1 mg
J0225	Injection, vutrisiran, 1 mg
E85.0	Non-neuropathic heredofamilial amyloidosis
E85.1	Neuropathic heredofamilial amyloidosis
E85.4	Organ-limited amyloidosis
E85.82	Wild-type transthyretin-related (ATTR) amyloidosis

Applicable ICD-10 diagnosis codesICD-10Covered

E85.0	Hereditary transthyretin-related amyloidosis
E85.4	Organ-limited amyloidosis
E85.82	Cardiac amyloidosis

Applicable ICD-10 diagnosis codesICD-10Covered

E85.0	Hereditary systemic amyloidosis
E85.4	Organ-limited amyloidosis
E85.82	Cardiac amyloidosis

PND, FAP, NIS, KPS thresholds — clinical baseline thresholds

Polyneuropathy Disability (PND)Baseline or continuing PND score ≤ IIIb

Familial Amyloid Polyneuropathy (FAP) StageBaseline or continuing FAP Stage 1 or 2

Neuropathy Impairment Score (NIS)Baseline or continuing NIS ≥ 5 and ≤ 130

Karnofsky Performance Status (KPS)Baseline or continuing KPS ≥ 60%

Authorization durationInitial and continuation authorization limited to no more than 12 months (per dosing in FDA prescribing information)

Definitions, Background, and Trials

Transthyretin (TTR) misfolding leads to extracellular amyloid fibril deposition in organs such as the heart and peripheral nerves, producing two major clinical presentations: restrictive cardiomyopathy (ATTR-CM) and progressive sensorimotor/autonomic polyneuropathy (hATTR). Cardiac involvement typically presents with symptoms of heart failure (eg, dyspnea, peripheral edema) and can be confirmed by genetic testing for pathogenic TTR variants, tissue biopsy demonstrating ATTR deposits, cardiac imaging suggestive of amyloidosis, or radionuclide scintigraphy with grade 2–3 myocardial uptake. RNA interference therapies such as vutrisiran and patisiran act by reducing hepatic TTR production and have demonstrated clinical benefit in randomized trials (for example, HELIOS-B for cardiomyopathy and APOLLO for polyneuropathy).

ATTR-CM definition

DefinitionCardiomyopathy due to transthyretin-mediated (wild-type or hereditary) amyloid deposition in the heart

Clinical featuresMay present with restrictive cardiomyopathy signs (dyspnea, peripheral edema, ascites) and progressive heart failure

EtiologyCaused by misfolded transthyretin (TTR) forming amyloid fibrils; occurs as wild-type (wtATTR) or hereditary/variant forms

Policy Summary

Payersierra health and life

PolicyRNA-Targeted Therapies (Amvuttra and Onpattro) — Coverage Criteria for ATTR amyloidosis

Policy CodePolicy 2025D0072N

Change TypeCriteria added and coverage stance revised (material)

Effective DateJun 1, 2025

Next Review DateN/A

SourceLink

On This Page

Step Therapy

Step therapy and prior tafamidis attempt/intolerance

Prior therapy expectations / step therapy: for ATTR-CM, provide documentation of progressive worsening or hospitalization related to ATTR-CM while on a transthyretin stabilizer (Vyndaqel/Vyndamax [tafamidis] or Attruby [acoramidis]), OR documentation of intolerance or contraindication to both tafamidis and acoramidis. Continuation requests must document prior treatment with Amvuttra and a positive clinical response.

Progression or hospitalization on tafamidis (Vyndaqel/Vyndamax) or acoramidis (Attruby) OR intolerance/contraindication to both
Continuation: previous Amvuttra treatment + documentation of positive clinical response (improved symptoms, quality of life, slowed progression, fewer hospitalizations)
Patient must continue to have NYHA class I–III for continuation

Step Therapy

Combination therapy exclusion

Combination therapy restrictions: Amvuttra must not be used in combination with other RNA interference agents (e.g., Onpattro/patisiran, Wainua/eplontersen, Tegsedi/inotersen) or with transthyretin stabilizers (e.g., tafamidis). Requests documenting combination use will not meet requirements.

Amvuttra not to be combined with other RNAi agents or transthyretin stabilizers
Equivalent combination exclusions apply reciprocally to other RNAi agents

Denial Risk

Denial triggers and documentation exclusions

Denial triggers: requests lacking required diagnostic confirmation (pathogenic TTR mutation, biopsy, or appropriate imaging), failure to exclude light-chain amyloidosis, absence of NYHA class I–III for ATTR-CM, missing NT-proBNP/clinical signs, failure to document prior therapy or intolerance where required, requests for combination therapy, dosing not consistent with FDA labeling, or requests exceeding 12 months may be denied.

Missing diagnostic confirmation or failure to exclude AL amyloidosis
No documentation of NYHA I–III or NT-proBNP when required
No documentation of progression/hospitalization on transthyretin stabilizer or intolerance where step therapy expected
Requests for combination therapy with other RNAi agents or stabilizers
Dosing not per FDA or authorization request > 12 months

HELIOS-B — additional key trial descriptors and endpoints

Primary outcome resultVutrisiran reduced risk of death from any cause and recurrent cardiovascular events vs placebo (HR 0.72; 95% CI 0.56–0.93; p=0.01)

Secondary mortality outcomeLower risk of death through 42 months (HR 0.65; 95% CI 0.46–0.90; p=0.01)

Functional secondary endpointsImproved 6-minute walk distance (LS mean difference 26.5 m; 95% CI 13.4–39.6; p<0.001) and improvements in KCCQ-OS

Study duration and randomization ratioUp to 36 months of follow-up; 1:1 randomization (vutrisiran:placebo)