Transthyretin-Mediated (ATTR) Amyloidosis — CPB 0939 | AETNA Coverage Update

TL;DR: Aetna, a CVS Health company, modified CPB 0939 governing ATTR amyloidosis drug coverage, effective November 11, 2025. Billing teams handling J0222 (patisiran), J0225 (vutrisiran), and related infusion codes need to review updated medical necessity criteria and combination therapy exclusions now.

This update to CPB 0939 in Aetna's system tightens the criteria for four high-cost RNA-targeting and antisense therapies used in hereditary transthyretin-mediated (hATTR) amyloidosis: patisiran (Onpattro), vutrisiran (Amvuttra), inotersen (Tegsedi), and eplontersen (Wainua). These are GCIT-designated products, which means Aetna's dedicated Gene-based, Cellular & Other Innovative Therapies team reviews every authorization request — not the standard pharmacy team. That distinction changes your precertification workflow, and if your team doesn't know it, you'll lose time and risk claim denial.

The Aetna ATTR amyloidosis coverage policy also addresses tafamidis (Vyndaqel, Vyndamax) and acoramidis (Attruby) as stabilizer-class agents, and pulls in a wide range of diagnostic codes — CPT 81404 for TTR gene sequencing, imaging codes 78800–78832 for nuclear medicine scans, and infusion administration codes 96365–96372. All of these carry billing implications that your revenue cycle team needs to review before submitting claims.

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Field	Detail
Payer	Aetna, a CVS Health company
Policy	Transthyretin-Mediated (ATTR) Amyloidosis — CPB 0939
Policy Code	CPB 0939
Change Type	Modified
Effective Date	November 11, 2025
Impact Level	High
Specialties Affected	Neurology, Cardiology, Genetics, Specialty Pharmacy, Infusion Centers
Key Action	Verify GCIT precertification routing and confirm combination therapy exclusions before billing J0222 or J0225

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Aetna ATTR Amyloidosis Coverage Criteria and Medical Necessity Requirements 2025

The Aetna ATTR amyloidosis coverage policy under CPB 0939 covers four drugs — but every single one has a distinct set of criteria. Don't treat these as interchangeable. The medical necessity bar is specific, and documentation gaps will generate denials fast on drugs that cost tens of thousands of dollars per infusion cycle.

Patisiran (Onpattro) — HCPCS J0222

For initial approval of patisiran IV infusion, Aetna requires all of the following:

That fourth criterion is the one that bites practices. Patients who are already on a stabilizer like tafamidis do not qualify for patisiran under this policy. Document the absence of concurrent therapy explicitly in your prior authorization submission.

For reauthorization, the member must show a beneficial response compared to baseline. Aetna specifically calls out the modified Neuropathy Impairment Scale+7 (mNIS+7), Norfolk QoL-DN total score, polyneuropathy disability (PND) score, FAP disease stage, and manual grip strength as acceptable measures. If your clinical team isn't capturing these at baseline, reauthorization will fail. Start tracking them at treatment initiation.

Patisiran must be prescribed by or in consultation with a neurologist, geneticist, or a physician specializing in amyloidosis. A general internist or hospitalist ordering this alone won't satisfy Aetna's prescriber requirement.

Eplontersen (Wainua) — Subcutaneous Injection

Eplontersen follows the same general structure: age 18+, confirmed pathogenic TTR variant, and no combination use with other agents in this class. The prescriber specialty requirement is identical — neurology, genetics, or amyloidosis specialist.

Eplontersen is a subcutaneous injection, which puts it on CPT 96369–96372 for administration rather than the IV infusion codes. Make sure your charge capture reflects the correct route. Billing 96365 (IV infusion) for a subcutaneous administration is a coding error that creates both a denial and a compliance exposure.

Vutrisiran (Amvuttra) — HCPCS J0225

Vutrisiran shares the same class-level exclusion from combination therapy. J0225 is billed per 1 mg. Given the typical dose, verify your NDC and quantity carefully before submitting. Aetna's Site of Care Utilization Management Policy also applies to Amvuttra — your billing team needs to confirm the approved site of service before scheduling the infusion. Administering in the wrong setting is a clean path to a claim denial with no clean appeal.

Inotersen (Tegsedi) — Specialty Pharmacy Route

Inotersen routes through specialty pharmacy precertification. Call (866) 752-7021 or fax (888) 267-3277. Submit the Statement of Medical Necessity form from Aetna's health care professional forms page. Don't skip the SMN — it's required, not optional, and missing it will hold up authorization indefinitely.

The GCIT Designation — Why It Matters for Your Workflow

All four drugs carry Aetna's GCIT designation. These requests go to a specialized internal team, not standard pharmacy review. Routing a GCIT authorization through the wrong channel adds days — sometimes weeks — to the approval timeline. Build this into your prior authorization workflow now, before the November 11, 2025 effective date catches a pending case off-guard.

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Aetna ATTR Amyloidosis Exclusions and Non-Covered Indications

Aetna considers all indications for these drugs outside the defined criteria to be experimental, investigational, or unproven. That's not a soft boundary. Any claim billed without meeting all required criteria — including the combination exclusion — gets denied on medical necessity grounds.

The combination therapy exclusion is the most operationally significant restriction here. A patient who takes acoramidis (Attruby) for cardiomyopathy and then develops polyneuropathy cannot receive patisiran under this policy while staying on Attruby. The drugs cannot be billed concurrently under any circumstances within this coverage policy. This isn't a step therapy requirement — it's a hard exclusion.

Tafamidis meglumine (Vyndaqel) and tafamidis (Vyndamax) are stabilizer-class agents listed in the combination exclusion. They appear across multiple drug criteria in CPB 0939. Any patient on either of these tafamidis products is ineligible for concurrent authorization of the RNA-targeting or antisense agents under this policy.

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Coverage Indications at a Glance

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Aetna ATTR Amyloidosis Billing Guidelines and Action Items 2025

These are the steps your billing and prior authorization teams need to take before November 11, 2025.

Copy Action Items

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CPT, HCPCS, and ICD-10 Codes for ATTR Amyloidosis Under CPB 0939

Covered HCPCS Codes (When Selection Criteria Are Met)

Code	Type	Description Copy
J0222	HCPCS	Injection, patisiran, 0.1 mg
J0225	HCPCS	Injection, vutrisiran, 1 mg

Additional HCPCS Codes Referenced in CPB 0939

These Technetium Tc-99m radiopharmaceutical codes (A9500–A9548) are associated with nuclear medicine imaging used in ATTR diagnosis and monitoring.

Covered CPT Codes Referenced in CPB 0939

Nuclear Medicine / Radiopharmaceutical Imaging

Molecular Pathology / Laboratory

Pathology / Special Stains

Drug Administration — Intravenous Infusion

Drug Administration — Subcutaneous Infusion

ICD-10-CM Codes

The policy data does not list specific ICD-10-CM codes for CPB 0939. Work with your coding team to assign the correct E85.x (amyloidosis) codes based on the documented disease type and manifestation. If your compliance officer is unsure which E85 subcategory applies to your patient population, confirm with your coding consultant before the effective date of November 11, 2025.

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