CurrentPremera BluecrossPolicy 5.01.593

Pharmacologic Treatment of Transthyretin-Mediated Amyloidosis

Defines medical necessity, site-of-service review, and coverage criteria for specific pharmacologic treatments (Amvuttra/vutrisiran, Onpattro/patisiran, Attruby/acoramidis, Vyndamax/Vyndaqel/tafamidis, Wainua/eplontersen) for hereditary or wild-type transthyretin-mediated amyloidosis, including age limits, diagnostic verification, exclusion criteria, dosing, benefit assignment (medical vs pharmacy), authorization durations, and reauthorization requirements. Also includes site-of-service medical necessity rules for infusion/injection administration.

Policy Summary

PayerPremera Bluecross

PolicyPharmacologic Treatment of Transthyretin-Mediated Amyloidosis

Policy CodePolicy 5.01.593

Change TypeCoverage criteria additions and diagnostic requirement updates

Effective DateJul 2, 202619d

Next Review Date

Key ActionDocument a TTR gene mutation or tissue biopsy (or non‑biopsy nuclear scintigraphy for ATTR-CM where allowed) and obtain required site-of-service/medical necessity review for IV/SC therapies.

SourceLink

POLICY UPDATE CHANGES

Added coverage criteria for Wainua (eplontersen) for treatment of hATTR-PN (2024 update).

Added coverage criteria for Attruby (acoramidis) for treatment of ATTR-CM (2025 update).

2026 update: Require documentation of TTR gene mutation or tissue biopsy for hATTR therapies and require TTR mutation, tissue biopsy, or non-biopsy nuclear scintigraphy for ATTR-CM therapies; removed requirement for two confirmatory diagnostic tests.

Removed Tegsedi (inotersen) from the medical policy after manufacturer withdrawal (Sept 27, 2024).

Policy revised with effective date Jul. 2, 2026; last revised Mar. 10, 2026.

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.

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.

6Listed drugs with coverage criteria

12Major required clinical thresholds listed

13Site-of-service age cutoff (years)

5Medications addressed in policy (historical/current)

2Diagnostic confirmation options required

2026Most recent major update year

Coverage Summary

This policy defines medical necessity and site-of-service review rules for pharmacologic treatments of transthyretin-mediated amyloidosis (hereditary hATTR and transthyretin-mediated cardiomyopathy, ATTR-CM). Drugs addressed include Amvuttra (vutrisiran), Onpattro (patisiran), Attruby (acoramidis), Vyndamax/Vyndaqel (tafamidis formulations), and Wainua (eplontersen), with benefit assignment as follows: Amvuttra and Onpattro under the medical benefit, Attruby and tafamidis products under the pharmacy benefit, and Wainua managed under both benefits.

Site-of-service medical necessity review applies to medical-benefit IV/injectable drugs (including Amvuttra and Onpattro) for individuals aged 13 years and older, and the policy establishes drug-specific diagnostic, exclusion, dosing, and specialist-prescribing requirements. Initial authorizations for listed agents may be approved for up to 12 months, with reauthorization contingent on documented continued efficacy and absence of treatment-limiting toxicity.

Quick facts & clinical thresholds

Age for site-of-service review>= 13 years

Age for medication indications>= 18 years

Echocardiography septal 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) requirement>= 150 meters

Polyneuropathy disability (PND) scorePND IIIb or less

Familial amyloid polyneuropathy (FAP) stageFAP stage 2 or less

Site-of-service hospital outpatient initial periodHospital-based outpatient medically necessary for first 90 days for initial course or re-initiation after >=6 months

Medical-Necessity Criteria

Site of Service Medical Necessity (general)

Site of service review applies to medical benefit IV/injectable drugs; applies to ages 13+ for site of service. Preferred medically necessary sites and hospital outpatient exceptions:

ALL of the following

Medically necessary sites of service
- Physician's office
- Infusion center
- Home infusion (IV infusion and injection therapy covered in most appropriate, safe, cost-effective site)
Hospital-based outpatient considered medically necessary when

Provider Actions & Administrative Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required for intravenous or subcutaneous therapies and for site-of-service review for members aged 13 and older. Providers must obtain prior authorization before dispensing or administering these agents.

Affected HCPCS/Codes: J0222, J0225, C9399, J3490
Applies to members aged 3E=A013 years
Effective date: July 2, 2026

Documentation Required

Diagnostic Verification Required

Diagnostic confirmation is required and must be documented in the medical record prior to initiation of therapy.

Document one of the following: a pathogenic or likely pathogenic TTR gene mutation OR tissue biopsy demonstrating amyloid deposition.
For ATTR-CM (cardiomyopathy), a non-biopsy nuclear scintigraphy consistent with transthyretin amyloid is an acceptable alternative to tissue biopsy when performed per guideline-concordant technique.

Coding

HCPCS / J-codes (medical benefit injectables/IV)HCPCS

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

HCPCS J-codes mentioned in historyHCPCS

J0222	HCPCS code added 10/1/19
J0225	HCPCS code for Amvuttra added 01/01/23
J3490	Added/removed at various history points for Tegsedi reporting
J3590	Removed for Amvuttra on 01/01/23 (historical)

Background, Evidence & Definitions

Hereditary transthyretin-mediated amyloidosis (hATTR) is a rare, progressive disorder caused by pathogenic variants in the TTR gene that destabilize transthyretin, leading to misfolding and extracellular amyloid fibril deposition in multiple organs (heart, peripheral nerves, GI tract, kidney). Clinical manifestations are heterogeneous and often mixed (polyneuropathy and cardiomyopathy), with common symptoms including numbness, pain, weakness, autonomic dysfunction, GI disturbance, cardiac manifestations, and carpal tunnel syndrome; disease course and age of onset vary considerably across patients.

Diagnosis can be challenging because signs and symptoms are nonspecific and variable; confirmation typically requires demonstration of amyloid deposition on tissue biopsy and/or identification of a pathogenic TTR variant. For ATTR-CM, noninvasive diagnosis with 99mTc-PYP (bone) scintigraphy is supported: in the absence of a light-chain abnormality, grade 2/3 cardiac uptake or an H/CL ratio > 1.5 is diagnostic of ATTR-CM with high specificity and positive predictive value.

Pharmacologic treatments target the underlying TTR pathology by either reducing hepatic TTR production (e.g., RNAi or antisense agents) or stabilizing the TTR tetramer to prevent misfolding and fibril formation. Given disease heterogeneity, therapies are applied using drug-specific clinical thresholds, diagnostic confirmation options, and exclusion criteria to select appropriate patients and monitor clinical benefit.

Study / Evidence	Key finding / size
HELIOS-A (vutrisiran hATTR-PN)	164 patients; vutrisiran improved mNIS+7 vs APOLLO placebo at 9 and 18 months (significant); major secondary outcomes also favored vutrisiran
HELIOS-B (vutrisiran ATTR-CM)	654 patients; vutrisiran reduced risk of all-cause mortality and recurrent CV events by 28% vs placebo (33% in monotherapy) and improved 6MWT and KCCQ-OS at Month 30
ATTR-ACT (tafamidis)	441 patients pooled; tafamidis superior to placebo on all-cause mortality and CV-related hospitalizations (p<0.001); ~30% mortality risk reduction
APOLLO (patisiran)	225 patients; patisiran improved mNIS+7 and quality-of-life measures vs placebo and reduced TTR levels
NEURO-TTRansform (eplontersen)	Interim 35-week analysis: significantly lowered serum TTR, lessened neuropathic impairment and improved quality of life vs placebo
Regulatory approvals cited	Patisiran (2018); Vutrisiran (2022 hATTR-PN; 2025 ATTR-CM); Eplontersen (Dec 2023 hATTR-PN); Tafamidis (2019 ATTR-CM); Acoramidis (Nov 2024 ATTR-CM)

Definitions

Definitions and quick reference:

ALL of the following

Revision History

2019-04-01policy_created

New policy created and approved (initial coverage for Onpattro and Tegsedi launched).

2023-12-01coverage_added

Added coverage criteria for Wainua (eplontersen) for treatment of hATTR‑PN (2024 update reflected in policy history).

2024-09-27product_removal

Removed Tegsedi (inotersen) from the medical policy after manufacturer withdrawal (product discontinued by manufacturer Sept 27, 2024).

Policy Summary

PayerPremera Bluecross

PolicyPharmacologic Treatment of Transthyretin-Mediated Amyloidosis

Policy CodePolicy 5.01.593

Change TypeCoverage criteria additions and diagnostic requirement updates

Effective DateJul 2, 202619d

Next Review Date

SourceLink

On This Page

No outpatient infusion center within 50 miles and no contracted home infusion agency will travel to home

Individual has a clinical condition increasing risk for infusion complications including any of: known symptomatic cardiac arrhythmia; significant respiratory disease or %FVC ≤ 40%; unstable renal function; difficult/unstable vascular access; acute mental status changes or cognitive conditions impacting safety

Hospital-based outpatient is medically necessary for individuals with known history of severe adverse drug reactions and/or anaphylaxis to prior related/similar drug

Cytokine release syndrome (CRS) criteria for hospital-based outpatient: CRS is grade 3 or 4 evidenced by ALL of: temperature ≥ 38 °C; hypotension requiring ≥1 vasopressors; hypoxia requiring high-flow oxygen device or positive pressure ventilation; AND individual will be admitted into an inpatient setting as soon as possible

Sites are not medically necessary when site-of-service criteria are not met

Amvuttra (vutrisiran) - polyneuropathy (hATTR-PN) Medical Necessity

Covered when ALL of the following are met:

ALL of the following

Medication: Amvuttra (vutrisiran) subcutaneous
Age: 18 years or older
Diagnosis verified by ONE of the following:
- Documentation of a mutation in the TTR gene
- Tissue biopsy showing amyloid deposition
Presence of symptoms consistent with polyneuropathy of hereditary transthyretin amyloidosis (peripheral sensorimotor polyneuropathy OR autonomic neuropathy)
Examples: tingling, pain, numbness, carpal tunnel, loss temperature sense, fine motor difficulty, leg weakness, difficulty walking; autonomic examples: postural hypotension, sexual dysfunction, recurrent UTI
Polyneuropathy disability (PND) score IIIb or less OR familial amyloid polyneuropathy (FAP) stage 2 or less
Combination therapy exclusion: Medication not used in combination with Attruby (acoramidis), Onpattro (patisiran), Vyndamax (tafamidis), Vyndaqel (tafamidis meglumine), or Wainua (eplontersen)
Individual must NOT have ANY of the following (exclusions)
- 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 treatment of ATTR amyloidosis (e.g., neurologist, cardiologist, geneticist)
Dose: 25 mg injected subcutaneously once every 3 months

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

Covered when ALL of the following are met:

ALL of the following

Medication: Amvuttra (vutrisiran) 25 mg SC q3 months
Age: 18 years or older
Diagnosis of wild-type or hereditary transthyretin-mediated amyloidosis verified by ONE of:
- Documentation of a mutation in the TTR gene
- Tissue biopsy showing amyloid deposition
- Non-biopsy nuclear scintigraphy
  See Related Information (99mTc-PYP scintigraphy)
Evidence of cardiac involvement: transthoracic echocardiography with end diastolic intraventricular septal wall thickness > 12 mm
Clinical heart failure requirement: Clinical history of heart failure with at least one prior hospitalization for heart failure OR clinical evidence of heart failure with volume overload or elevated intracardiac pressures warranting diuretic treatment
Baseline NT-proBNP ≥ 300 pg/mL
NYHA class I-III heart failure
Exclusions (must NOT have any):
- Presence of light-chain amyloidosis
- History of liver or heart transplantation
- Left ventricular assist device
Completed 6-minute walk test (6MWT) of at least 150 meters
Combination therapy exclusion: Medication not used in combination with Attruby, Onpattro, Vyndamax, Vyndaqel, or Wainua
Medication prescribed by or in consultation with physicians experienced in treatment of ATTR amyloidosis (e.g., neurologist, cardiologist, geneticists)

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

Managed under pharmacy benefit. Covered when ALL of the following are met:

ALL of the following

Medication: Attruby (acoramidis) oral
Age: 18 years or older
Diagnosis verified by ONE of:
- Documentation of a mutation in the TTR gene
- Tissue biopsy showing amyloid deposition
- Non-biopsy nuclear scintigraphy
  See Related Information
Evidence of cardiac involvement: transthoracic echocardiography with end diastolic intraventricular septal wall thickness > 12 mm
Clinical heart failure requirement: Clinical history of heart failure with at least one prior hospitalization for heart failure OR clinical evidence of heart failure with volume overload or elevated intracardiac pressures warranting diuretics
Baseline NT-proBNP ≥ 300 pg/mL
NYHA class I-III heart failure
Exclusions (must NOT have any):
- Presence of light-chain amyloidosis
- History of liver or heart transplantation
- Left ventricular assist device
Completed 6-minute walk test (6MWT) of at least 150 meters
Combination therapy exclusion: Medication is not used in combination with Amvuttra, Onpattro, Vyndamax, Vyndaqel, or Wainua
Specialist prescribing: Medication prescribed by or in consultation with physicians experienced in treatment of ATTR amyloidosis (e.g., neurologist, cardiologist, geneticist)
Dose: 712 mg orally twice daily

Onpattro (patisiran) - polyneuropathy (hATTR-PN) Medical Necessity

Managed under medical benefit. Covered when ALL of the following are met:

ALL of the following

Medication: Onpattro (patisiran) IV
Age: 18 years or older
Diagnosis verified by ONE of:
- Documentation of a mutation in the TTR gene
- Tissue biopsy showing amyloid deposition
Presence of symptoms consistent with polyneuropathy of hATTR (peripheral sensorimotor polyneuropathy OR autonomic neuropathy)
Examples provided in policy
PND score IIIb or less OR FAP stage 2 or less
Combination therapy exclusion: Medication not used in combination with Attruby, Amvuttra, Vyndamax, Vyndaqel, or Wainua
Exclusions (must NOT have any):
- 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
Specialist prescribing: Medication prescribed by or in consultation with physicians experienced in treatment of ATTR amyloidosis
Dose based on actual body weight:
- Individuals < 100 kg: 0.3 mg/kg IV once every 3 weeks
- Individuals ≥ 100 kg: 30 mg IV once every 3 weeks

Vyndamax / Vyndaqel (tafamidis) - cardiomyopathy (ATTR-CM) Medical Necessity

Managed under pharmacy benefit. Covered when ALL of the following are met:

ALL of the following

Medication: Vyndamax (tafamidis) or Vyndaqel (tafamidis meglumine)
Age: 18 years or older
Diagnosis verified by ONE of:
- Documentation of a mutation in the TTR gene
- Tissue biopsy showing amyloid deposition
- Non-biopsy nuclear scintigraphy
  See Related Information (e.g., PYP scintigraphy)
Evidence of cardiac involvement: transthoracic echocardiography with end diastolic intraventricular septal wall thickness > 12 mm
Clinical heart failure requirement: Clinical history of heart failure with at least one prior hospitalization for heart failure OR clinical evidence of heart failure with volume overload or elevated intracardiac pressures warranting diuretics
Baseline NT-proBNP ≥ 600 pg/mL
NYHA class I-III heart failure
Exclusions (must NOT have any):
- Presence of light-chain amyloidosis
- History of liver or heart transplantation
- Left ventricular assist device
Completed 6-minute walk test (6MWT) of at least 150 meters
Combination therapy exclusion: Medication is not used in combination with Attruby, Amvuttra, Onpattro, or Wainua
Specialist prescribing: Medication prescribed by or in consultation with physicians experienced in treatment of ATTR amyloidosis
Dose for Vyndamax: 61 mg orally once daily; Dose for Vyndaqel: 80 mg orally once daily

Wainua (eplontersen) - polyneuropathy (hATTR-PN) Medical Necessity

Managed under pharmacy and medical benefit. Covered when ALL of the following are met:

ALL of the following

Medication: Wainua (eplontersen) subcutaneous
Age: 18 years or older
Diagnosis verified by ONE of:
- Documentation of a mutation in the TTR gene
- Tissue biopsy showing amyloid deposition
Presence of symptoms consistent with polyneuropathy of hATTR (peripheral sensorimotor polyneuropathy OR autonomic neuropathy)
Examples provided in policy
PND score IIIb or less OR FAP stage 2 or less
Combination therapy exclusion: Medication not used in combination with Attruby, Amvuttra, Onpattro, Vyndamax, or Vyndaqel
Exclusions (must NOT have any):
- 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
Specialist prescribing: Medication prescribed by or in consultation with physicians experienced in treatment of ATTR amyloidosis
Dose: 45 mg injected subcutaneously every 4 weeks

Investigational / Not covered uses

All other uses not outlined in this policy are considered investigational.

Any use of Amvuttra, Attruby, Onpattro, Vyndamax, Vyndaqel, or Wainua for conditions not outlined in this policy is investigational.

Authorization durations and re-authorization criteria

Initial and re-authorization rules:

ALL of the following

Initial authorization: All drugs listed in policy may be approved up to 12 months
Re-authorization for Amvuttra, Onpattro, Wainua (hATTR): Approved for 12 months if drug-specific criteria are met and individual has shown and continues to show efficacy documented in medical record (examples: improved or stable motor, neurologic, cardiac function, or serum TTR levels) AND improvement or stability in PND score or FAP stage from baseline AND absence of treatment-limiting toxicity
Re-authorization for Amvuttra, Attruby, Vyndamax, Vyndaqel (ATTR-CM): Approved for 12 months if criteria met and individual has shown and continues to show efficacy documented in medical record (examples: 6MWT, KCCQ-OS)

Coverage criteria for hATTR (polyneuropathy) - Amvuttra, Onpattro, Wainua

Covered when ALL of the following are met:

ALL of the following

Confirmation of diagnosis by ONE of
- Documentation of a mutation in the TTR gene
- Tissue biopsy showing amyloid deposition
Exclusion NYHA: Does not have NYHA class III or IV heart failure
Policy history notes updated criteria
Does not have sensorimotor or autonomic neuropathy not related to hereditary transthyretin-mediated amyloidosis
No prior liver transplantation
Specialist prescribing: Medications must be prescribed by or in consultation with physicians experienced in the treatment of ATTR amyloidosis (e.g., neurologist, cardiologist, geneticists)
Combination rule for Wainua: For Wainua specifically: May not be used in combination with Amvuttra, Onpattro, or Tegsedi

Coverage criteria for ATTR-CM (cardiomyopathy) - Amvuttra, Attruby, Vyndamax/Vyndaqel

Covered when ALL of the following are met:

ALL of the following

Diagnosis of transthyretin-mediated amyloid cardiomyopathy (ATTR-CM)
Confirmation of cardiac diagnosis by ONE of
- Documentation of a mutation in the TTR gene
- Tissue biopsy showing amyloid deposition
- Non-biopsy nuclear scintigraphy (e.g., PYP scintigraphy)
  See Related Information (99mTc-PYP)
LVAD exclusion: Does not have a left ventricular assist device (LVAD)
Replaced previous 'implanted cardiac device' wording
Cardiac assessment: Assessment of cardiac involvement and history of heart failure as required by product-specific criteria (e.g., end-diastolic interventricular septal wall thickness > 12 mm, baseline NT-proBNP thresholds, 6MWT requirement for tafamidis products)
Specialist prescribing: Medications must be prescribed by or in consultation with physicians experienced in the treatment of ATTR amyloidosis (e.g., neurologist, cardiologist, geneticists)
6MWT requirement: 6-minute walk test (6MWT) requirement was added for tafamidis products in prior updates and is part of assessment of cardiac involvement>=150 meters

General policy-level restrictions and product-specific notes

ALL of the following

Medications listed are subject to the product's FDA dosage and administration prescribing information
Non-formulary exception length: Non-formulary exception review authorizations for all drugs listed may be approved up to 12 months
Tegsedi removal: Tegsedi (inotersen) was removed from the policy after market withdrawal (Sept 27, 2024) and is not covered
Historical quantity limits note: Quantity limits were added for Vyndamax and Vyndaqel in prior updates; providers must follow product-specific quantity limits as specified by plan/formulary

Document clinical evidence of disease: transthoracic echocardiography, baseline NT-proBNP, 6-minute walk test (6MWT) where applicable, and neurologic staging such as PND or FAP.

Documentation Required

Specialist Prescribing or Consultation

Prescriptions must be written by or accompanied by consultation with clinicians experienced in ATTR amyloidosis management.

Prescribing or consult required from a neurologist, cardiologist, or medical geneticist (or other clinician experienced in ATTR management).
Documentation of the specialist consultation or that the prescriber has expertise in ATTR must be in the medical record.

Billing Rule

Benefit Assignment / Billing Rules

Benefit assignment varies by product; use the medical or pharmacy benefit as specified when billing.

Medical benefit (typically billed via HCPCS): Onpattro (patisiran), Amvuttra (vutrisiran). See HCPCS codes J0222 and J0225 as applicable.
Pharmacy benefit: Attruby (acoramidis), Vyndamax (tafamidis), Vyndaqel (tafamidis meglumine).
Both medical and pharmacy benefit (coverage may vary by plan): Wainua (eplontersen).
Verify member-specific benefit and formulary prior to dispensing or administration.

Denial Risk

Combination Therapy Exclusion

Combination therapy with certain TTR-directed agents is not permitted and may result in claim denial.

Wainua (eplontersen) may not be used concomitantly with Amvuttra (vutrisiran), Onpattro (patisiran), or Tegsedi (inotersen) (Tegsedi currently withdrawn; prohibition remains).
Amvuttra, Onpattro, and other TTR-lowering agents should not be used in combination with Attruby (acoramidis) or tafamidis products unless specifically allowed by policy.
Claims for medications used in prohibited combinations may be denied.

Documentation Required

Re-authorization Evidence

Re-authorization (continuation) requires documentation of continued benefit and absence of unacceptable toxicity.

Evidence of improvement or stability in motor, neurologic, or cardiac function compared with baseline (examples: 6MWT distance, KCCQ-OS for cardiomyopathy, PND/FAP stage).
Laboratory evidence where applicable (e.g., serum TTR levels when measured per clinical practice).
Documentation of absence of drug-related toxicity that would necessitate discontinuation.
Ongoing specialist follow-up documentation.

Prior Authorization

Site-of-Service Review for IV Therapies

Site-of-service review applies to intravenous therapies; providers will be notified of site-of-service decisions.

Effective date for site-of-service review: July 2, 2026.
A 90-day provider notification period applies for changes affecting Amvuttra and Onpattro site-of-service requirements.
Site-of-service determinations follow the policy's medical necessity criteria (physician office, infusion center, home infusion, or hospital outpatient as specified).

Billing Rule

Quantity Limits

Quantity limits are enforced for oral tafamidis products and other formulary-specified agents.

Vyndamax (tafamidis) and Vyndaqel (tafamidis meglumine) are subject to quantity limits per the plan/formulary.
Prescribers must follow plan- and formulary-specified quantity limits and refill/dispense rules.

Documentation Required

No Combination Therapy for Wainua

Specific prohibition reiterated: Wainua must not be co-administered with other TTR-lowering oligonucleotide or RNAi agents.

Wainua (eplontersen) may not be used concurrently with Amvuttra (vutrisiran), Onpattro (patisiran), or Tegsedi (inotersen; withdrawn).
Documented monotherapy with Wainua is required; concurrent use may result in denial.

PND score: Polyneuropathy disability score with clinical descriptions from 0 (no symptoms) to IV (wheelchair/bedridden); policy requires IIIb or less

FAP stage: Familial amyloid polyneuropathy stage 0-3 with stage 2 = assistance with ambulation; policy requires stage 2 or less

NYHA class: New York Heart Association functional classification I-IV for heart failure; several criteria exclude NYHA III-IV

6MWT: 6-minute walk test; policy requires completion of at least 150 meters for ATTR-CM criteria>=150 meters

NT-proBNP: N-terminal pro b-type natriuretic peptide; numeric thresholds specified per drug (>=300 or >=600 pg/mL)variable per drug

hATTR: Hereditary transthyretin-mediated amyloidosis (polyneuropathy form)

ATTR-CM: Transthyretin-mediated amyloid cardiomyopathy (wild-type or variant)

Wild type (TTR): Policy note: wild type means the TTR protein is normal, with no documented mutations

2024-11-01regulatory_update

Attruby (acoramidis) FDA approval noted (Nov 2024) and coverage criteria planning initiated (policy history documents addition in 2025).

2025-02-01coverage_added

Added coverage criteria for Attruby (acoramidis) for treatment of ATTR‑CM (2025 update).

2026-03-10last_review

Policy last reviewed (annual review) and changes finalized March 10, 2026 (updated diagnostic confirmation and other criteria).

2026-07-02policy_effectiveLatest

Effective date for 2026 updates (material): require documentation of a TTR gene mutation or tissue biopsy for hATTR therapies; require TTR mutation, tissue biopsy, or non‑biopsy nuclear scintigraphy for ATTR‑CM therapies; added site‑of‑service review for Amvuttra and Onpattro; changed exclusion wording from 'implanted cardiac device' to 'left ventricular assist device'; clarified prescribing by or in consultation with experienced physicians. Marked as material and current effective date.

2026-07-02administrative_updateLatest

Policy header updated with effective date Jul 2, 2026 and last review Mar 10, 2026 (administrative revision; clarifications on FDA dosing and non-formulary exception length retained).