ModifiedPremera BluecrossPolicy 5.01.593

Pharmacologic Treatment of Transthyretin-Mediated Amyloidosis

Defines medical necessity coverage criteria, dosing, exclusions, re-authorization and documentation requirements for multiple TTR-directed therapies for hATTR polyneuropathy and ATTR cardiomyopathy, including management under pharmacy and/or medical benefits.

Policy Summary

PayerPremera Bluecross

PolicyPharmacologic Treatment of Transthyretin-Mediated Amyloidosis

Policy CodePolicy 5.01.593

Change TypeUpdated diagnostic confirmation, added Attruby, removed Tegsedi

Effective DateApr 1, 2026

Next Review Date

Key ActionProvide documentation of a TTR gene mutation OR tissue biopsy showing amyloid deposition (or non-biopsy nuclear scintigraphy for ATTR-CM where specified) in medical records submitted for review.

SourceLink

POLICY UPDATE CHANGES

Added coverage criteria for Attruby (acoramidis) for the treatment of ATTR-CM in adults.

Updated coverage criteria for Amvuttra, Onpattro, and Wainua for hATTR to require documentation of a TTR gene mutation or tissue biopsy and removed requirement for two confirmatory diagnostic tests.

Updated coverage criteria for Amvuttra, Attruby, Vyndamax, and Vyndaqel for ATTR-CM to require documentation of a TTR mutation, tissue biopsy, or non-biopsy nuclear scintigraphy and removed requirement for two confirmatory diagnostic tests.

Removed Tegsedi (inotersen) from the medical policy.

Clarified that medications are subject to FDA dosage and administration prescribing information and that non-formulary exception reviews may be approved up to 12 months.

Removed requirement for two confirmatory diagnostic tests and replaced with requirement of TTR gene mutation or tissue biopsy (and for ATTR-CM optionally non-biopsy nuclear scintigraphy) for multiple drugs.

Changed exclusion wording from 'does not have an implanted cardiac device' to 'does not have a left ventricular assist device' for certain ATTR-CM therapies.

Allowed prescribing by or in consultation with physicians experienced in treating ATTR amyloidosis.

Tegsedi (inotersen) removed from policy due to market withdrawal (02/01/25 history).

Added coverage criteria and a new indication for Amvuttra for ATTR-CM (07/01/25 history).

6Drugs covered with criteria

1Drug removed (Tegsedi)

12Authorization months (max)

150 m6MWT minimum (meters)

3Diagnostic options for ATTR-CM

5Drugs referenced

Coverage Summary

Scope: This policy defines medical necessity coverage criteria, dosing, exclusions, re-authorization and documentation requirements for multiple TTR-directed therapies used to treat hereditary transthyretin-mediated amyloidosis (hATTR) with polyneuropathy and transthyretin amyloid cardiomyopathy (ATTR-CM). Covered drugs include Amvuttra (vutrisiran) and Onpattro (patisiran) for hATTR polyneuropathy; Wainua (eplontersen) for hATTR polyneuropathy; and Attruby (acoramidis) and tafamidis products (Vyndamax/Vyndaqel) for ATTR-CM. Tegsedi (inotersen) has been removed from the policy (product withdrawn).

Coverage stance: The policy takes a mixed coverage stance — specific drugs and indications are covered when detailed diagnostic, clinical, and functional criteria are met (see drug-specific sections). Benefit management is split by drug: Amvuttra and Onpattro are managed under the medical benefit, Attruby and tafamidis products are managed under the pharmacy benefit, and Wainua is managed under both pharmacy and medical benefits.

Key program rules: Diagnostic confirmation requirements vary by indication (for hATTR: documentation of a TTR gene mutation OR tissue biopsy showing amyloid deposition; for ATTR-CM: documentation of a TTR gene mutation OR tissue biopsy showing amyloid deposition OR non-biopsy nuclear scintigraphy). Combination use of listed TTR-directed therapies is disallowed per drug-specific criteria. Device exclusion for certain ATTR-CM therapies is specified as no left ventricular assist device.

Authorizations and limits: Initial approvals and re-authorizations for the listed drugs may be approved for up to 12 months; re-authorization requires documented ongoing efficacy and absence of treatment-limiting toxicity. Functional thresholds used in criteria include end-diastolic interventricular septal wall thickness > 12 mm, baseline NT-proBNP thresholds (e.g., >= 300 pg/mL for some agents, >= 600 pg/mL for tafamidis criteria), and a completed 6-minute walk test (6MWT) of at least 150 meters for ATTR-CM agents.

Selected thresholds and quick facts

Echocardiography septal wall thickness> 12 mm (end-diastolic interventricular septal wall thickness)

Baseline NT-proBNP (Amvuttra, Attruby)>= 300 pg/mL

Baseline NT-proBNP (Vyndamax/Vyndaqel)>= 600 pg/mL

6-Minute Walk Test (6MWT) minimum>= 150 meters

PND score requirement (hATTR polyneuropathy)IIIb or less

FAP stage requirement (hATTR polyneuropathy)Stage 2 or less

Initial authorization maximumUp to 12 months

Medical-Necessity Criteria (by drug and indication)

Amvuttra (vutrisiran) - hATTR polyneuropathy

Amvuttra (vutrisiran) may be considered medically necessary for the treatment of polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR) when ALL of the following are met:

The individual is aged 18 years or older.

Diagnosis of hereditary transthyretin-mediated amyloidosis is verified by documentation of a mutation in the TTR gene OR tissue biopsy showing amyloid deposition.

Presence of symptoms consistent with polyneuropathy of hereditary transthyretin amyloidosis (peripheral sensorimotor polyneuropathy such as tingling, pain, numbness, loss of temperature sensation, difficulty with fine motor skills, weakness, difficulty walking OR autonomic neuropathy such as postural hypotension, sexual dysfunction, recurrent urinary tract infections).

Polyneuropathy disability (PND) score IIIb or less OR familial amyloid polyneuropathy (FAP) stage 2 or less.

Investigational / Not Covered Indications

Investigational / Not covered indications

Drugs listed are considered investigational for uses not outlined in this policy.

ANY of the following

Amvuttra (vutrisiran) - all other uses not specified in policy are investigational
Attruby (acoramidis) - all other uses not specified in policy are investigational
Onpattro (patisiran) - all other uses not specified in policy are investigational
Vyndamax (tafamidis) / Vyndaqel (tafamidis meglumine) - all other uses not specified in policy are investigational

Authorization and Re-authorization Criteria

Initial authorization and Re-authorization

Authorization periods and re-authorization criteria:

ALL of the following

Initial authorization: All drugs listed may be approved up to 12 monthsUp to 12 months
Re-authorization for hATTR
- May be approved for 12 months if drug-specific criteria are met and individual has shown and continues to show efficacy documented in medical record indicating positive clinical response (e.g., improved or stable motor, neurologic, cardiac function, or serum TTR levels)
- Improvement or stability in one of the following from baseline: PND score or FAP stagePND or FAP stability/improvement

Coverage Criteria Updates (Summary)

Coverage criteria updates (general summary from this part)

Policy was updated to revise diagnostic confirmation requirements and other inclusion/exclusion criteria for multiple drugs; specifics vary by indication and drug.

ALL of the following

hATTR diagnostic change: For treatment of hATTR (polyneuropathy) with Amvuttra, Onpattro, Wainua: documentation of a mutation in the TTR gene OR tissue biopsy showing amyloid deposition (replaced prior requirement of two confirmatory diagnostic tests)
ATTR-CM diagnostic change: For treatment of ATTR-CM with Amvuttra, Attruby, Vyndamax, Vyndaqel: documentation of a mutation in the TTR gene OR tissue biopsy showing amyloid deposition OR non-biopsy nuclear scintigraphy (removed requirement to have two confirmatory diagnostic tests)
LVAD wording change: For Amvuttra, Attruby, Vyndamax, and Vyndaqel for ATTR-CM: does not have a left ventricular assist device (previously phrased as does not have an implanted cardiac device)

Coding

HCPCS / J-codes / UnclassifiedHCPCS

C9399	Unclassified drugs or biologicals (used to report: Wainua)
J0222	Injection, patisiran (Onpattro), 0.1 mg
J0225	Injection, vutrisiran (Amvuttra), 1 mg
J3490	Unclassified drugs (use to report: Wainua)

Previously recorded HCPCS/J-codes referenced in historyHCPCS

J0222	HCPCS code added 10/01/19 (historical coding update)
J0225	HCPCS code for Amvuttra added 01/01/23
J3490	Generic code historically used; removed/updated in policy history
J3590	Generic code removed 11/01/20 (historical)

Provider Actions / Prior Authorization & Documentation

Documentation Required

Diagnosis verification required

Diagnosis verification required: Confirm the diagnosis of hereditary or wild-type transthyretin-mediated amyloidosis with genetic testing showing a TTR gene mutation or tissue biopsy demonstrating amyloid deposition; non-biopsy nuclear scintigraphy may be used for ATTR-CM where indicated.

Documentation Required

Functional status documentation

Functional status documentation: Document baseline and follow-up functional measures relevant to the indication—examples include PND score or FAP stage for polyneuropathy and NYHA class, NT-proBNP, 6-minute walk test distance, and echocardiographic parameters for cardiomyopathy.

Background & Evidence

Background: Hereditary transthyretin-mediated amyloidosis (hATTR) is a rare, progressive disorder caused by pathogenic variants in the TTR gene leading to misfolded transthyretin protein and extracellular amyloid deposition in multiple organs including peripheral nerves and the heart. Clinical manifestations include progressive sensorimotor and autonomic neuropathy, cardiac dysfunction, and gastrointestinal and other organ involvement. If untreated, median survival after symptom onset can be limited (death reported about 5–15 years in polyneuropathy cohorts).

Diagnostic challenges: Diagnosis is often delayed because signs and symptoms are heterogeneous and nonspecific, frequently mimicking other conditions. Confirmatory testing historically relies on tissue biopsy demonstrating amyloid (Congo red and confirmatory methods) and genetic testing for pathogenic TTR variants. For ATTR-CM, non-biopsy cardiac bone scintigraphy using 99mTc-PYP (or other 99mTc bone-avid compounds) is diagnostic in the absence of a monoclonal protein when there is grade 2/3 uptake or an H/CL ratio > 1.5, facilitating noninvasive confirmation of ATTR-CM.

Prevalence and natural history: hATTR is uncommon but likely under-diagnosed; estimates note at least ~10,000 people worldwide with >120 TTR mutations reported and ~3,000–5,000 people in the U.S., though true prevalence may be higher due to diagnostic challenges. The disease is progressive with variable organ involvement and can lead to substantial morbidity and mortality.

Rationale for TTR-directed therapies: TTR-directed agents include TTR silencers (e.g., small interfering RNA and antisense oligonucleotides) and stabilizers. Clinical trials demonstrate meaningful benefits: vutrisiran (Amvuttra) and patisiran (Onpattro) reduced neuropathy progression in hATTR polyneuropathy trials (HELIOS-A, APOLLO) and vutrisiran reduced risk of all-cause mortality and recurrent cardiovascular events and improved 6MWT and KCCQ-OS in ATTR-CM (HELIOS-B). Tafamidis (Vyndamax/Vyndaqel) reduced all-cause mortality and cardiovascular-related hospitalizations in ATTR-CM (ATTR-ACT). Eplontersen (Wainua) lowered serum TTR and improved neuropathic impairment and quality of life in hATTR-PN (NEURO-TTRansform). These efficacy data support disease-specific coverage criteria.

Definitions

Term	Definition
PND score	Polyneuropathy disability score: 0 none; I sensory disturbances but preserved walking; II impaired walking without stick/crutch; IIIA one stick; IIIB two sticks; IV wheelchair/bedridden.
FAP stage	Familial amyloid polyneuropathy staging: 0 no symptoms; 1 unimpaired ambulation; 2 assistance with ambulation required; 3 wheelchair-bound or bedridden.
NYHA class	New York Heart Association functional classification I-IV for heart failure symptoms.
Non-biopsy nuclear scintigraphy	99mTc-PYP or other 99mTc bone-avid cardiac scintigraphy diagnostic of ATTR-CM when grade 2/3 uptake or H/CL ratio >1.5 in absence of monoclonal protein.
Wild type	TTR protein is normal, with no documented mutations (policy note defining 'wild type').

Revision History

08/01/22historical

Added Amvuttra (vutrisiran) coverage for polyneuropathy of hATTR; specified combination therapy exclusions (not to be used with Onpattro, Tegsedi).

03/01/24historical

Added Wainua (eplontersen) coverage for certain adults with hATTR polyneuropathy and added combination therapy exclusions with Amvuttra, Onpattro, and Tegsedi.

02/01/25material

Added coverage criteria for Attruby (acoramidis) for ATTR-CM; removed Tegsedi (inotersen) from the policy due to market withdrawal; added 6MWT requirement and quantity limits for tafamidis products; removed NYHA class IV exclusion for tafamidis.

Policy Summary

PayerPremera Bluecross

PolicyPharmacologic Treatment of Transthyretin-Mediated Amyloidosis

Policy CodePolicy 5.01.593

Change TypeUpdated diagnostic confirmation, added Attruby, removed Tegsedi

Effective DateApr 1, 2026

Next Review Date

SourceLink

On This Page

Medication is not used in combination with Attruby (acoramidis), Onpattro (patisiran), Vyndamax (tafamidis), Vyndaqel (tafamidis meglumine), or Wainua (eplontersen).

The individual does not have ANY of the following: New York Heart Association (NYHA) class III or IV heart failure; sensorimotor or autonomic neuropathy not related to hATTR (e.g., monoclonal gammopathy or autoimmune disease); prior liver transplantation.

Medication is prescribed by or in consultation with physicians experienced in the treatment of ATTR amyloidosis (e.g., neurologist, cardiologist, geneticist).

Dose prescribed is 25 mg injected subcutaneously once every 3 months.

Note: Clinical description of PND score — Score 0 = No symptoms; Score I = Sensory disturbances but preserved walking capability; Score II = Impaired walking capacity but ability to walk without a stick or crutches; Score IIIA = Walking with the help of one stick or crutch; Score IIIB = Walking with the help of two sticks or crutches; Score IV = Confined to a wheelchair or bedridden.

Note: Clinical description of FAP stage — Stage 0 = No symptoms; Stage 1 = Unimpaired ambulation; Stage 2 = Assistance with ambulation required; Stage 3 = Wheelchair-bound or bedridden.

Amvuttra (vutrisiran) - ATTR cardiomyopathy (ATTR-CM)

Amvuttra (vutrisiran) may be considered medically necessary for the treatment of cardiomyopathy of wild type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) when ALL of the following are met:

The individual is aged 18 years or older.

Diagnosis of wild type or hereditary transthyretin-mediated amyloidosis is verified by documentation of a mutation in the TTR gene OR tissue biopsy showing amyloid deposition OR non-biopsy nuclear scintigraphy.

Evidence of cardiac involvement as assessed with transthoracic echocardiography, with end diastolic intraventricular septal wall thickness greater than 12 mm.

Clinical history of heart failure with at least one previous hospitalization for heart failure OR clinical evidence of heart failure with volume overload or elevated intracardiac pressures warranting diuretic treatment.

Has a baseline N-terminal pro b-type natriuretic peptide (NT-proBNP) of greater than or equal to 300 pg/mL.

Has New York Heart Association (NYHA) class I-III heart failure.

Does not have any of the following: presence of light-chain amyloidosis; history of liver or heart transplantation; left ventricular assist device (LVAD).

Completed a 6-minute-walk test (6MWT) of at least 150 meters.

Medication is not used in combination with Attruby (acoramidis), Onpattro (patisiran), Vyndamax (tafamidis), Vyndaqel (tafamidis meglumine), or Wainua (eplontersen).

Medication is prescribed by or in consultation with physicians experienced in the treatment of ATTR amyloidosis (e.g., neurologist, cardiologist, geneticists).

Dose prescribed is 25 mg injected subcutaneously once every 3 months.

Onpattro (patisiran) - hATTR polyneuropathy

Onpattro (patisiran) may be considered medically necessary for the treatment of polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR) when ALL of the following are met:

The individual is aged 18 years or older.

Diagnosis of hereditary transthyretin-mediated amyloidosis is verified by documentation of a mutation in the TTR gene OR tissue biopsy showing amyloid deposition.

Presence of symptoms consistent with polyneuropathy of hereditary transthyretin amyloidosis (peripheral sensorimotor polyneuropathy OR autonomic neuropathy as described for hATTR).

Polyneuropathy disability (PND) score IIIb or less OR familial amyloid polyneuropathy (FAP) stage 2 or less.

Medication is not used in combination with Attruby (acoramidis), Amvuttra (vutrisiran), Vyndamax (tafamidis), Vyndaqel (tafamidis meglumine), or Wainua (eplontersen).

Medication is prescribed by or in consultation with physicians experienced in the treatment of ATTR amyloidosis (e.g., neurologist, cardiologist, geneticist).

Dose is based on actual body weight as follows: For individuals weighing less than 100 kg, the dosage is 0.3 mg/kg IV once every 3 weeks; For individuals weighing 100 kg or more, the dosage is 30 mg IV once every 3 weeks.

Note: Clinical description of PND score and FAP stage (see Amvuttra hATTR polyneuropathy notes).

Attruby (acoramidis) - ATTR cardiomyopathy (ATTR-CM)

Attruby (acoramidis) may be considered medically necessary for the treatment of cardiomyopathy of wild type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) when ALL of the following are met:

The individual is aged 18 years or older.

Evidence of cardiac involvement as assessed with transthoracic echocardiography, with end diastolic intraventricular septal wall thickness greater than 12 mm.

Has a baseline N-terminal pro b-type natriuretic peptide (NT-proBNP) of greater than or equal to 300 pg/mL.

Has New York Heart Association (NYHA) class I-III heart failure.

Does not have any of the following: presence of light-chain amyloidosis; history of liver or heart transplantation; left ventricular assist device (LVAD).

Completed a 6-minute-walk test (6MWT) of at least 150 meters.

Medication is not used in combination with Amvuttra (vutrisiran), Onpattro (patisiran), Vyndamax (tafamidis), Vyndaqel (tafamidis meglumine), or Wainua (eplontersen).

Medication is prescribed by or in consultation with physicians experienced in the treatment of ATTR amyloidosis (e.g., neurologist, cardiologist, geneticist).

Dose prescribed for Attruby (acoramidis) is 712 mg orally twice daily.

Note: Wild type means the TTR protein is normal, with no documented mutations.

Vyndamax / Vyndaqel (tafamidis) - ATTR-CM

Vyndamax (tafamidis) or Vyndaqel (tafamidis meglumine) may be considered medically necessary for the treatment of cardiomyopathy of wild type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) when ALL of the following are met:

The individual is aged 18 years or older.

Evidence of cardiac involvement as assessed with transthoracic echocardiography, with end diastolic intraventricular septal wall thickness greater than 12 mm.

Has a baseline N-terminal pro b-type natriuretic peptide (NT-proBNP) of greater than or equal to 600 pg/mL.

Has New York Heart Association (NYHA) class I-III heart failure (note: NYHA IV exclusion removed).

Does not have any of the following: presence of light-chain amyloidosis; history of liver or heart transplantation; left ventricular assist device (LVAD).

Completed a 6-minute-walk test (6MWT) of at least 150 meters.

Medication is not used in combination with Amvuttra (vutrisiran), Onpattro (patisiran), Attruby (acoramidis), or Wainua (eplontersen).

Medication is prescribed by or in consultation with physicians experienced in the treatment of ATTR amyloidosis (e.g., neurologist, cardiologist, geneticist).

Dose for Vyndaqel (tafamidis meglumine) is 80 mg orally once daily.

Wainua (eplontersen) - hATTR polyneuropathy

Wainua (eplontersen) may be considered medically necessary for the treatment of polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR) when ALL of the following are met:

The individual is aged 18 years or older.

Diagnosis of hereditary transthyretin-mediated amyloidosis is verified by documentation of a mutation in the TTR gene OR tissue biopsy showing amyloid deposition.

Presence of symptoms consistent with polyneuropathy of hereditary transthyretin amyloidosis (peripheral sensorimotor polyneuropathy OR autonomic neuropathy as described for hATTR).

Medication is not used in combination with Attruby (acoramidis), Amvuttra (vutrisiran), Onpattro (patisiran), Vyndamax (tafamidis), or Vyndaqel (tafamidis meglumine).

Medication is prescribed by or in consultation with physicians experienced in the treatment of ATTR amyloidosis (e.g., neurologist, cardiologist, geneticist).

Dose prescribed is 45 mg subcutaneously every 4 weeks.

Historical coverage criterion changes (select)

Historical coverage criterion changes (select):

Revision effective 2026-04-01: NT-proBNP threshold for Vyndamax/Vyndaqel raised to >= 600 pg/mL; NYHA IV exclusion removed for Vyndamax/Vyndaqel.

Revision effective 2026-04-01: Added non-biopsy nuclear scintigraphy option for diagnosis verification for ATTR-CM across applicable agents.

Revision effective 2026-04-01: Added explicit prohibition on concomitant use across listed TTR-directed therapies for all agents.

Revision effective 2026-04-01: Clarified echocardiography septal wall thickness threshold as > 12 mm for ATTR-CM criteria.

Revision effective 2026-04-01: Updated dosing for Attruby to 712 mg twice daily; confirmed Amvuttra dosing 25 mg SC every 3 months; confirmed Onpattro weight-based IV dosing; confirmed Wainua 45 mg every 4 weeks.

Wainua (eplontersen) - all other uses not specified in policy are investigational

Tegsedi (inotersen) removed from policy (product withdrawn) and not covered

Product withdrawn and not covered

Absence of treatment limiting toxicity

Re-authorization for ATTR-CM

May be approved for 12 months if applicable criteria are met and individual has shown and continues to show efficacy documented in medical record (e.g., 6MWT, KCCQ-OS score)6MWT or KCCQ-OS response

Wild type clarification: Clarification that 'wild type' means the TTR protein is normal with no documented mutations.

Prescriber allowance: Medications may be prescribed by or in consultation with physicians experienced in the treatment of ATTR amyloidosis (examples: neurologist, cardiologist, geneticist).

Removed two-test requirement: Updated policy criteria for Amvuttra, Onpattro, and Wainua for hATTR require documentation of a TTR mutation or tissue biopsy and removed requirement for two confirmatory tests.

08/01/22added

Added coverage criteria for Amvuttra (vutrisiran) for polyneuropathy of hATTR (Amvuttra not to be used in combination with certain other TTR therapies).

03/01/24added

Added coverage criteria for Wainua (eplontersen) for polyneuropathy of hATTR and specified combination therapy exclusions with Amvuttra, Onpattro, and Tegsedi.

02/01/25added/revised/removed

Added coverage criteria for Attruby (acoramidis) for ATTR-CM; updated diagnosis and tafamidis criteria (6MWT requirement, quantity limits), removed NYHA class IV exclusion for tafamidis, and removed Tegsedi (inotersen) from the policy due to market withdrawal.

07/01/25added

Added a new indication for Amvuttra (vutrisiran) for the treatment of ATTR-CM.

04/01/26 (approved Mar 10, 2026)revisedLatest

Updated coverage criteria for hATTR drugs (Amvuttra, Onpattro, Wainua) to require documentation of a TTR gene mutation or tissue biopsy and removed requirement for two confirmatory diagnostic tests; updated ATTR-CM criteria (Amvuttra, Attruby, Vyndamax, Vyndaqel) to require TTR mutation, tissue biopsy, or non-biopsy nuclear scintigraphy and removed requirement for two confirmatory diagnostic tests; changed 'implanted cardiac device' wording to 'left ventricular assist device'; allowed prescribing by or in consultation with physicians experienced in ATTR amyloidosis.

Prior Authorization

Prior authorization / prescribing oversight

Prior authorization / prescribing oversight: Prior authorization is required. Initial approvals may be granted for up to 12 months. Reauthorization requires documentation of continued clinical benefit (efficacy) and absence of significant toxicity during the prior authorization period.

Billing Rule

Benefit management

Benefit management: Products are managed under the following benefits: Amvuttra (vutrisiran) and Onpattro (patisiran) — medical benefit; Attruby (acoramidis) and tafamidis products (Vyndamax/Vyndaqel) — pharmacy benefit; Wainua (eplontersen) — may be managed under both medical and pharmacy benefits depending on site of care and billing.

Denial Risk

Combination therapy exclusion

Combination therapy exclusion: Claims may be denied if the requested medication is used in combination with other specified transthyretin (TTR)-targeted therapies. The policy excludes simultaneous use of two or more of the listed TTR-directed agents (e.g., Amvuttra, Onpattro, Attruby/acoramidis, Vyndamax/Vyndaqel/tafamidis meglumine, Wainua).

Documentation Required

Medical record documentation for ATTR-CM agents

Medical record documentation for ATTR-CM agents: Submit office visit notes and documentation that include relevant history and physical examination findings demonstrating the criteria are met for the requested indication (e.g., diagnostic confirmation, cardiac involvement measures, NYHA class, NT-proBNP, 6MWT, prior hospitalizations for heart failure).

Documentation Required

Left ventricular assist device exclusion for ATTR-CM therapies

Left ventricular assist device exclusion for ATTR-CM therapies: Individuals with a left ventricular assist device (LVAD) are excluded from coverage of ATTR-CM therapies per policy criteria; document device status in the medical record.

Billing Rule

Medication quantity limits (historical)

Medication quantity limits (historical): Quantity limits were added for tafamidis products effective 02/01/2025. Prescribers must follow FDA dosing and any policy-specific quantity limits when submitting requests.

Study/Label	Key findings
HELIOS-A (vutrisiran hATTR-PN)	Vutrisiran improved mNIS+7 and multiple secondary outcomes versus comparator/placebo; noninferior TTR reduction vs patisiran
HELIOS-B (vutrisiran ATTR-CM)	Reduced risk of all-cause mortality and recurrent CV events (28% overall; 33% monotherapy); improved 6MWT and KCCQ-OS at Month 30
ATTR-ACT (tafamidis)	Pooled tafamidis superior to placebo for all-cause mortality and CV-related hospitalization over 30 months (win ratio 1.695; p<0.001)
APOLLO (patisiran)	Patisiran improved mNIS+7 and quality of life measures versus placebo
NEURO-TTRansform (eplontersen)	Wainua lowered serum TTR, lessened neuropathic impairment, and improved QoL versus placebo at 35-week interim analysis
Attruby (acoramidis)	Acoramidis (712 mg twice daily) reduced all-cause mortality and cardiovascular-related hospitalizations versus placebo over 30 months (primary composite significant, p=0.018)
References included	Multiple prescribing information documents and peer-reviewed literature cited (policy references list prescribing information and key trials)

07/01/25material

Added a new indication for Amvuttra (vutrisiran) for the treatment of ATTR-CM.

04/01/26 (approved Mar 10, 2026)materialLatest

Updated coverage criteria for Amvuttra, Onpattro, and Wainua (hATTR) to require documentation of a TTR gene mutation or tissue biopsy (removed requirement for two confirmatory diagnostic tests); updated ATTR-CM criteria for Amvuttra, Attruby, Vyndamax, and Vyndaqel to require documentation of a TTR gene mutation, tissue biopsy, or non-biopsy nuclear scintigraphy (removed requirement for two confirmatory diagnostic tests); changed device exclusion wording to 'left ventricular assist device'; clarified 'wild type' meaning; allowed prescribing by or in consultation with physicians experienced in treating ATTR amyloidosis.