ModifiedmhnPolicy CP.PHAR.405

Clinical Policy: Inotersen (Tegsedi)

Clinical coverage policy for inotersen (Tegsedi) for treatment of polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR) in adults, including initial and continuation criteria, dosing limits, contraindications, REMS, coding notes, and product discontinuation notice.

Policy Summary

Payermhn

PolicyClinical Policy: Inotersen (Tegsedi)

Policy CodePolicy CP.PHAR.405

Change TypeMODIFIED

Effective DateNov 20, 2018

Next Review Date

Key ActionProvider must submit documentation (e.g., office chart notes, lab results) supporting that member has met all approval criteria.

POLICY UPDATE CHANGES

Added requirement that Tegsedi is not prescribed concurrently with Onpattro (and later Amvuttra and Wainua).

Added active HCPCS codes C9399 and J3490 to coding implications.

Manufacturer will discontinue commercial availability of Tegsedi effective September 27, 2024.

Removed criterion 'member has not received prior treatment with Amvuttra, Onpattro, or Wainua'.

1FDA-approved indication(s)

284 mg/weekMaximum weekly dose

>=100 x10^9/LPlatelet count requirement

2024-09-27Commercial discontinuation date

Coverage Summary & Scope

Clinical coverage policy for inotersen (Tegsedi) for treatment of polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR) in adults, detailing initial and continuation criteria including diagnosis, confirmation of a transthyretin (TTR) mutation, biopsy or justification, neurologist prescriber requirement, age ≥ 18 years, no prior liver transplant, platelet monitoring, dosing limits, REMS requirements, coding notes, and manufacturer discontinuation notice. The policy includes a platelet threshold of ≥ 100 x 10^9 /L for initial and continued approval and a maximum weekly dose of ≤ 284 mg (1 syringe) per week. Tegsedi is listed as covered with criteria and the manufacturer will discontinue commercial availability effective 2024-09-27.

FDA-approved indications1

Maximum weekly dose284 mg/week

Platelet count requirement>= 100 x 10^9 /L

Commercial discontinuation date2024-09-27

Initial Therapy — Hereditary Transthyretin‑Mediated Amyloidosis

Initial Therapy — Hereditary Transthyretin-Mediated Amyloidosis

It is medically necessary when ALL of the following are met:

ALL of the following

Diagnosis of hATTR with polyneuropathy
Documentation confirms presence of a transthyretin (TTR) mutation
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
Prescribed by or in consultation with a neurologist
Age ≥ 18 years

Initial Therapy — Other Diagnoses / Indications

Initial Therapy — Other diagnoses/indications

If requested use is not covered by main criteria, must meet one of the following:

ANY of the following

If this drug has recently (within the last 6 months) undergone a label change that is not yet reflected in this policy, follow formulary/no-coverage or non-formulary policy references per line of business
See referenced policies for commercial, HIM/marketplace, Medicaid
If the requested use is not listed and no recent label change applies, refer to off-label use policy per line of business
See referenced policies for commercial, HIM/marketplace, Medicaid

Continuation Therapy — Hereditary Transthyretin‑Mediated Amyloidosis

Continuation Therapy — Hereditary Transthyretin-Mediated Amyloidosis

Member must meet ALL of the following for continued coverage:

ALL of the following

ONE of
- Currently receiving medication via Centene benefit or member has previously met initial approval criteria
- Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B)
Recent (dated within the last month) platelet count ≥ 100 x 10^9 /L>= 100 x 10^9 /L

Continuation Therapy — Other Diagnoses / Indications

Continuation Therapy — Other diagnoses/indications

Same referral pathways as initial other-indication criteria:

ANY of the following

Follow formulary/no-coverage or non-formulary policy references if recent label change applies
Refer to CP.CPA.190, HIM.PA.33/HIM.PA.103, CP.PMN.255/CP.PMN.16 per line of business
Refer to off-label use policy if use not listed and no recent label change applies
Refer to CP.CPA.09, HIM.PA.154, CP.PMN.53 per line of business

Not Authorized / Exclusions

Not Authorized

Diagnoses/Indications for which coverage is NOT authorized:

Non‑FDA approved indications which are not addressed in this policy, unless sufficient documentation of efficacy and safety per off-label use policies or evidence of coverage documents

Boxed warnings include thrombocytopenia and glomerulonephritis, and Tegsedi is available only through the Tegsedi REMS restricted distribution program.

Provider Actions & Prior Authorization Requirements

Prior Authorization

Prescriber specialty requirement

Initial approval requires the medication to be prescribed by or in consultation with a neurologist.

Documentation Required

Submit supporting documentation

Providers must submit supporting documentation such as office chart notes and laboratory results demonstrating that the member meets all approval criteria.

Office chart notes
Laboratory results (including platelet counts)
Other clinical information as needed

Applicable Codes

HCPCS / J-code billing descriptors referencedHCPCS

J3490	Unclassified drugs
C9399	Unclassified drugs or biologicals

Coding implications reference active HCPCS / J-code billing descriptors including C9399 and J3490, which are noted in the policy's coding section and revision history.

Clinical Evidence & References

Key clinical evidence includes the Tegsedi Prescribing Information (Jan 2024) and the pivotal randomized trial reported by Benson et al. in the New England Journal of Medicine (2018) evaluating inotersen for hATTR with polyneuropathy.

Background & Definitions

Inotersen (Tegsedi) is a transthyretin-directed antisense oligonucleotide indicated for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR) in adults. The policy identifies boxed warnings for thrombocytopenia and glomerulonephritis and states Tegsedi is available only through the Tegsedi REMS Program. The manufacturer will discontinue commercial availability of Tegsedi effective September 27, 2024, and Appendix D advises providers to transition patients to alternative commercially available therapies. The recommended dosing regimen for hATTR with polyneuropathy is 284 mg subcutaneously once weekly (maximum 284 mg/week), and platelet monitoring with recent platelet count ≥ 100 x 10^9 /L is required for initiation and continuation.

hATTRhereditary transthyretin-mediated amyloidosis

REMSRisk Evaluation and Mitigation Strategy (restricted distribution program)

BNP / NT-proBNPB-type natriuretic peptide / N-terminal pro-B-type natriuretic peptide

Revision History

2Q 2024added

Added Wainua to the list of drugs that should not be previously received or prescribed concurrently with Tegsedi (concurrent‑therapy restriction).

2Q 2024added

Added active HCPCS codes C9399 and J3490 to coding implications.

2024-09-27manufacturer_action

Manufacturer (Akcea Therapeutics, Inc.) will discontinue commercial availability of Tegsedi effective September 27, 2024; providers instructed to transition patients to alternative therapies (Appendix D).

Policy Summary

Payermhn

PolicyClinical Policy: Inotersen (Tegsedi)

Policy CodePolicy CP.PHAR.405

Change TypeMODIFIED

Effective DateNov 20, 2018

Next Review Date

Key ActionProvider must submit documentation (e.g., office chart notes, lab results) supporting that member has met all approval criteria.

On This Page

Member has not had a prior liver transplant

Recent (dated within the last month) platelet count ≥ 100 x 10^9 /L>= 100 x 10^9 /L

Tegsedi is not prescribed concurrently with Amvuttra, Onpattro, or Wainua

Dose does not exceed 284 mg (1 syringe) per week<= 284 mg/week

Member is responding positively to therapy - including but not limited to improvement in any of the following parameters: Neuropathy (motor function, sensation, reflexes, walking ability); Nutrition (body mass index); Cardiac parameters (Holter monitoring, echocardiography, electrocardiogram, plasma BNP or NT-proBNP, serum troponin); Renal parameters (creatinine clearance, urine albumin); Ophthalmic parameters (eye exam)

Member has not had a prior liver transplant

Tegsedi is not prescribed concurrently with Amvuttra, Onpattro, or Wainua

If request is for a dose increase, new dose does not exceed 284 mg (1 syringe) per week<= 284 mg/week

Documentation Required

Platelet monitoring requirement

Provide a recent platelet count dated within the last month showing a platelet count ≥ 100 x 10^9 /L for both initial and continued approvals.

Documentation Required

Demonstrate clinical response for continuation

For continuation requests, document positive clinical response to therapy with improvement in neuropathy, nutritional, cardiac, renal, or ophthalmic parameters.

Neuropathy: motor function, sensation, reflexes, walking ability
Nutrition: body mass index
Cardiac: Holter, echocardiography, ECG, BNP/NT-proBNP, troponin
Renal: creatinine clearance, urine albumin
Ophthalmic: eye exam

Billing Rule

Dose limit enforcement

Dose requests and any dose increases must not exceed 284 mg (one prefilled syringe) per week.

Denial Risk

Contraindication checks

Claims may be denied if the member has a platelet count below 100 x 10^9 /L, a history of acute glomerulonephritis caused by Tegsedi, or a history of hypersensitivity to Tegsedi.

Documentation Required

REMS program requirement

Tegsedi is available only through the Tegsedi REMS Program; providers must adhere to REMS requirements and the restricted distribution program.

2Q 2025removedLatest

Removed criterion that a member has not received prior treatment with Amvuttra, Onpattro, or Wainua (per competitor analysis).