RNA-Targeted Therapies (Amvuttra and Onpattro) — Medical Benefit Drug Policy (Ohio-only)
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This policy governs medical benefit coverage and prior authorization criteria for Amvuttra (vutrisiran) and Onpattro (patisiran) for treatment of ATTR cardiomyopathy and hereditary ATTR polyneuropathy — applicable to UnitedHealthcare Community Plan members in Ohio.
Supporting Information Updated References section to reflect the most current information
Coverage Criteria — Indications and Requirements
Amvuttra for ATTR cardiomyopathy — Initial therapy
Covered when ALL of the following are met:
Amvuttra for ATTR cardiomyopathy — Continuation therapy
Covered when ALL of the following are met:
Amvuttra or Onpattro for hATTR polyneuropathy — Initial therapy
Covered when ALL of the following are met:
Amvuttra or Onpattro for hATTR polyneuropathy — Continuation therapy
Covered when ALL of the following are met:
Clinical evidence summaries
Clinical evidence summarized from APOLLO and other studies showing efficacy and safety endpoints
LS mean differences: GLS +1.4% (p=0.02); basal region +2.1% (p=0.006); LV wall thickness -0.9 mm (p=0.017); NT-proBNP fold-change ratio 0.45 (p<0.001)
Authors concluded patisiran may halt or reverse cardiac manifestations of hATTR
mNIS+7 difference -17.0 (p<0.001); Norfolk QoL-DN and 10MWT improvements reported
Per the policy, Amvuttra (vutrisiran) and Onpattro (patisiran) are considered unproven and not medically necessary when used for sensorimotor or autonomic neuropathy not related to hereditary transthyretin‑mediated (hATTR) amyloidosis. This exclusion is explicit in the coverage section addressing non‑hATTR neuropathies.
The document does not treat FDA approval as determinative of coverage; the FDA information is provided for reference only. Coverage and prior authorization decisions must follow applicable federal, state (Ohio Administrative Code), or contractual benefit plan requirements, which may differ from this policy. Benefits and contract terms may therefore vary, and providers should verify member‑specific coverage before proceeding.
The policy explicitly states that treatment of sensorimotor or autonomic neuropathy not related to hATTR amyloidosis and of primary or leptomeningeal amyloidosis with Amvuttra or Onpattro is not medically necessary. These specific disease states are listed as noncovered indications in the coverage criteria.
Within the FDA informational section and other explanatory text of this document segment, there are no additional explicit statements labeled as not medically necessary beyond those specified elsewhere in the coverage criteria. FDA labeling is presented for information and does not itself establish coverage.
Billing and Diagnosis Codes
| E85.1 | |
| E85.4 | Organ-limited amyloidosis |
| E85.82 | Wild-type transthyretin-related (ATTR) amyloidosis |
Prior Authorization, Documentation, and Operational Rules
Prior authorization required (Ohio) — limited to ≤12 months
Prior authorization is required for members in Ohio; initial and continuation authorizations must be for no more than 12 months and dosing must follow the FDA prescribing information.
Interpret policy in context of member benefit — verify per contract
This Medical Benefit Drug Policy is intended to assist interpretation of UnitedHealthcare standard benefit plans; prior authorization requirements and medical necessity must be determined per the member’s federal, state (OAC), or contractual benefit plan and may use third‑party criteria.
- Check the member’s benefit contract to determine whether prior authorization is required.
- UnitedHealthcare may use tools such as InterQual to assist administration.
Document intolerance/contraindication to tafamidis and Attruby when required
For certain indications, the policy requires documentation of intolerance or contraindication to transthyretin stabilizers (e.g., tafamidis) and Attruby before permitting alternative therapy; combination use with other TTR‑targeting agents is disallowed.
- Document intolerance or contraindication to Vyndaqel/Vyndamax (tafamidis) and Attruby (acoramidis) when requested by the policy.
- Do not prescribe Amvuttra or Onpattro in combination with other RNAi agents or TTR stabilizers per policy restrictions.
No additional step therapy specified in policy text
No explicit step therapy sequencing (beyond intolerance/contraindication documentation) is specified in this policy segment.
- Providers should still confirm member‑specific step requirements via the benefit contract.
Required clinical documentation — diagnosis and confirmatory evidence
Provide documentation to support diagnosis: for ATTR‑CM, document wild‑type or hereditary ATTR cardiomyopathy and confirmatory evidence (pathogenic TTR mutation OR cardiac/noncardiac tissue biopsy showing ATTR deposits OR echocardiogram/MRI suggestive of amyloidosis plus grade 2–3 radionuclide cardiac uptake and absence of light‑chain amyloidosis). For hATTR polyneuropathy, document pathogenic TTR mutation plus baseline clinical scores (PND ≤ IIIb OR FAP stage 1–2 OR NIS 5–130 OR KPS ≥60%) and signs/symptoms.
- For ATTR‑CM: include genotype, biopsy report, or imaging with radionuclide scan grade 2–3 and statement excluding light‑chain amyloidosis.
- For hATTR polyneuropathy: include genetic test confirming pathogenic TTR mutation and baseline PND, FAP, NIS, or KPS scores as applicable.
Run documentation and benefit checks against federal/state/contractual rules
When requesting coverage, reference and comply with federal, state (Ohio Administrative Code), or contractual benefit plan requirements; UnitedHealthcare may use third‑party tools to verify and administer benefits.
- Check OAC 5160‑1‑01 and the member’s contract when services are stated as unproven or limited.
- UnitedHealthcare reserves the right to modify policies and may use tools such as InterQual for administration.
Common triggers for denial — combination therapy, missing diagnostics, benefit noncompliance
Common denial triggers include: use in combination with other RNA interference agents or transthyretin stabilizers; failure to meet diagnostic confirmation criteria for ATTR‑CM or hATTR polyneuropathy; and failure to follow prior authorization or Ohio‑specific medical necessity rules.
- Combination therapy with other RNAi agents (e.g., patisiran, eplontersen, inotersen) or TTR stabilizers (e.g., tafamidis) is prohibited and may lead to denial.
- Missing required diagnostic documentation (genotype, biopsy, appropriate imaging with grade 2–3 uptake, or baseline clinical scores) can trigger denial.
- Not following prior authorization or OAC/contractual requirements may result in denial.
FDA approval alone does not guarantee coverage — verify governing benefit rules
FDA approval is informational only and is not, by itself, a basis for coverage; coverage decisions must reference applicable federal, state (OAC), or contractual benefit requirements which govern in case of conflict.
- Do not assume FDA approval guarantees coverage — verify against the member’s plan and OAC regulations.
- In the event of conflict, federal/state/contractual requirements govern over this policy.
Background and Scope
Transthyretin‑mediated (ATTR) amyloidosis results from misfolding of the transthyretin (TTR) protein with extracellular deposition of amyloid fibrils in tissues, most commonly the heart and peripheral nerves. Clinical manifestations depend on the dominant organ involvement: ATTR cardiomyopathy (ATTR‑CM) produces a restrictive cardiomyopathy with progressive heart failure symptoms such as dyspnea and edema, while hereditary ATTR (hATTR) amyloidosis may present with progressive sensorimotor polyneuropathy and autonomic dysfunction. Amvuttra (vutrisiran) and Onpattro (patisiran) are transthyretin‑directed small interfering RNA therapies that reduce serum TTR by targeting TTR mRNA; their use in this policy is limited to the labeled indications for hATTR polyneuropathy and ATTR cardiomyopathy as specified under the coverage criteria and subject to documentation and authorization requirements.
Definitions and Key Terms
Policy Revision History
Supporting Information Updated References section to reflect the most current information; archived previous policy version CSOH2025D0072.C.
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