CurrentmhnPolicy CP.PHAR.633

Eplontersen (Wainua) Clinical Policy

Defines medical necessity criteria, dosing limits, approval durations, and coding guidance for eplontersen (Wainua) for treatment of polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults across Commercial, HIM, and Medicaid lines of business.

Policy Summary

Payermhn

PolicyEplontersen (Wainua) Clinical Policy

Policy CodePolicy CP.PHAR.633

Change TypeFDA approval; criteria and coding updates

Effective DateDec 21, 2023

Next Review Date

Key ActionProvider must submit documentation (office chart notes, lab results, or other clinical information) supporting that member meets all approval criteria.

POLICY UPDATE CHANGES

RT4: drug is now FDA approved - criteria updated per FDA labeling; added HCPCS codes C9399 and J3490.

3Q 2024 annual review: removed Tegsedi from criteria as agent will be discontinued September 2024.

2Q 2025 annual review: removed criteria 'member has not received prior treatment with Onpattro or Amvuttra' per competitor analysis; references reviewed and updated.

Policy created pre-emptively on 05.01.23 with P&T approval 08.23.

1FDA Approved Indication

45 mg/monthMaximum Dose

≥18Minimum Age (yrs)

6-12 moApproval Duration

Coverage Summary

Scope: Defines medical necessity criteria, dosing limits, approval durations, and coding guidance for eplontersen (Wainua) for treatment of polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults. Coverage stance: covered_with_criteria. FDA‑approved indication: treatment of polyneuropathy of hereditary TTR‑mediated amyloidosis in adults. Age requirement: Age ≥18 years. Maximum dose: 45 mg once monthly (45 mg/month). Genetic confirmation via DNA sequencing is usually required and Congo red tissue biopsy is used to confirm amyloid deposits; a negative biopsy does not exclude disease.

Initial Therapy — Medical Necessity Criteria

I. Initial Approval Criteria - Hereditary Transthyretin-Mediated Amyloidosis

must meet all

ALL of the following

Hereditary Transthyretin-Mediated Amyloidosis (must meet all)
- Diagnosis of hereditary TTR-mediated amyloidosis with polyneuropathy
- Documentation confirms presence of a TTR mutation
  DNA sequencing is usually required for genetic confirmation
- Biopsy is positive for amyloid deposits or medical justification is provided as to why treatment should be initiated despite a negative biopsy or no biopsy
  Congo red staining demonstration of amyloid deposits; negative biopsy does not exclude disease
- Prescribed by or in consultation with a neurologist
- Age ≥ 18 years≥ 18 years
- Member has not had a prior liver transplant
- Wainua is not prescribed concurrently with Onpattro or Amvuttra
- Dose does not exceed 45 mg once monthly≤ 45 mg once monthly
  Maximum dose 45 mg/month

Approval duration

Medicaid/HIM approval duration: 6 months
Commercial approval duration: 6 months or to the member's renewal date, whichever is longer

I. Initial Approval Criteria - Approval duration

Approval duration

Medicaid/HIM approval duration: 6 months
Commercial approval duration: 6 months or to the member's renewal date, whichever is longer

I.B. Other diagnoses/indications

must meet 1 or 2

1: If the drug has recently (within the last 6 months) undergone a label change not yet reflected in this policy, follow formulary/no-coverage or non-formulary policy as applicable (refer to CP.CPA.190, HIM.PA.33, CP.PMN.255, HIM.PA.103, CP.PMN.16 as appropriate)
2: If requested use is NOT specifically listed under section III AND criterion 1 above does not apply, refer to off-label use policy for the relevant line of business (CP.CPA.09, HIM.PA.154, CP.PMN.53)

Continuation (Renewal) Criteria

II. Continuation (Renewal) Criteria - Hereditary TTR-mediated amyloidosis

must meet all

Hereditary TTR-mediated amyloidosis (continuation)

a or b
- a: Currently receiving medication via Centene benefit or member has previously met initial approval criteria
- b: Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums CC.PHARM.03A and CC.PHARM.03B)
Member is responding positively to therapy as evidenced by, including but not limited to, improvement in measures of polyneuropathy (e.g., motor strength, sensation, and reflexes), quality of life, motor function, walking ability, and nutritional status (e.g., as evaluated by modified mass index)

Not Authorized / Exclusions

III. Diagnoses/Indications NOT authorized

III. Diagnoses/Indications NOT authorized: Non‑FDA approved indications which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to off-label use policies (CP.CPA.09, HIM.PA.154, CP.PMN.53) or evidence of coverage documents

Explicit exclusion: Wainua is not to be prescribed concurrently with Onpattro or Amvuttra. Note: a prior-treatment exclusion (member has not received prior treatment with Onpattro or Amvuttra) was removed per 2Q 2025 review; concurrent-prescription requests remain denial risk and will be denied if prescribed concurrently as described in provider actions.

Applicable Codes

HCPCS - informationalHCPCS

C9399	Unclassified drugs or biologicals
J3490	Unclassified drugs

Provider Actions & Billing Rules

Prior Authorization

Submit documentation for medical necessity

Provider must submit documentation (office chart notes, lab results, or other clinical information) supporting that the member meets all approval criteria.

Documentation Required

Genetic confirmation and biopsy documentation

Provide documentation confirming presence of a TTR mutation and either a biopsy positive for amyloid deposits or medical justification for initiating treatment despite a negative biopsy or no biopsy.

Clinical Evidence

EfficacyJAMA 2023 reports demonstrated clinically meaningful benefit for eplontersen in hereditary TTR-mediated polyneuropathy (NEURO-TTRansform results)

DoseApproved dosing for polyneuropathy: 45 mg SC once monthly (maximum 45 mg/month)

Key evidence: the pivotal trial NEURO-TTRansform (NCT04136184) and the JAMA 2023 publication (Eplontersen for Hereditary Transthyretin Amyloidosis With Polyneuropathy) demonstrate efficacy of eplontersen for hereditary TTR amyloidosis with polyneuropathy. Note: Tegsedi was removed from criteria in the 3Q 2024 review.

Background

Background: Eplontersen (Wainua) is a transthyretin‑directed antisense oligonucleotide indicated for treatment of polyneuropathy of hereditary TTR‑mediated amyloidosis in adults. DNA sequencing is usually required for genetic confirmation, and tissue biopsy with Congo red staining is used to demonstrate amyloid deposits; however, negative biopsy results should not be interpreted as excluding the disease.

Quick facts and thresholds

Minimum ageAge ≥ 18 years

Maximum dose45 mg once monthly (45 mg/month)

Approval duration (Medicaid/HIM)6 months (initial); 12 months (continuation)

Approval duration (Commercial)6 months or to member's renewal date, whichever is longer

Policy numberCP.PHAR.633

Effective date

Definitions

Definitions: TTR = transthyretin.

Revision History

05.01.23policy created

Policy created pre-emptively; P&T Approval Date 08.23.

01.09.24material - approval and coding update

RT4: drug is now FDA approved - criteria updated per FDA labeling; added HCPCS codes C9399 and J3490.

02.12.24references reviewed

2Q 2024 annual review: references reviewed and updated (no significant changes).