ModifiedAnthemPolicy CC-0084

Medical Drug Clinical Criteria - Tegsedi (inotersen)

Clinical criteria for medical-benefit coverage and prior authorization of Tegsedi (inotersen) for treatment of polyneuropathy of hereditary transthyretin-mediated (hATTR) amyloidosis in adults, including initial and continuation criteria, exclusions, quantity limits, coding guidance, and safety monitoring references.

Policy Summary

PayerAnthem

PolicyMedical Drug Clinical Criteria - Tegsedi (inotersen)

Policy CodePolicy CC-0084

Change TypeRevised (clinical & coding updates)

Effective DateOct 1, 2025

Next Review Date

Key ActionPrior authorization requests must include diagnosis, genotyping-confirmed TTR mutation, polyneuropathy status, baseline and recent platelet and UPCR labs, and for continuation evidence of clinical improvement or stabilization.

SourceLink

POLICY UPDATE CHANGES

8/15/2025 - Annual Review: Add diagnosis criteria to continuation criteria; remove renal and hepatic exclusions; add Attruby to may not be used in combination criteria; administrative update to add documentation; coding reviewed: removed ICD-10-CM E85.2-E85.9, G62.9; updated HCPCS descriptions.

8/16/2024 - Annual Review: Add Wainua to may not be used in combination criteria.

8/21/2020 - Annual Review: Add continuation criteria to Tegsedi clinical criteria and add quantity limit.

2Therapy stages with criteria (initial, continuation)

6Explicit exclusion criteria listed

4Monitoring lab thresholds specified

4Prohibited concomitant amyloidosis agents listed

Coverage Summary

Coverage: covered_with_criteria for Tegsedi (inotersen) for treatment of polyneuropathy of hereditary transthyretin-mediated (hATTR) amyloidosis in adults per clinical criteria. Effective date: 2025-10-01. Last review: 2025-08-15. The policy includes initial and continuation criteria (diagnosis, TTR genotyping, documentation of mild-to-moderate polyneuropathy, baseline and ongoing laboratory thresholds for platelets and UPCR), quantity limit (4 syringes per 28 days), coding guidance, and required REMS enrollment. The manufacturer has discontinued Tegsedi but the clinical criteria remain active to allow adjudication of claims through September 2026.

Initial therapy - Medical necessity

Initial requests for Tegsedi (inotersen) may be approved if the following criteria are met:

ALL of the following

Individual has a diagnosis of hereditary transthyretin (hATTR) amyloidosis or familial amyloid polyneuropathy (FAP)
Documentation is provided that individual has a TTR mutation verified by genotyping (Benson, 2018)
Documentation is provided that individual has associated mild to moderate polyneuropathy (Benson, 2018)
Individual has a baseline platelet count greater than or equal to 100 x 10^9 /L>= 100 x 10^9 /L
Contraindicated if platelet count < 100 x 10^9 /L per black box warning
Individual has a urinary protein to creatinine ratio (UPCR) less than 1000 mg/gUPCR < 1000 mg/g
Do not initiate if UPCR >= 1000 mg/g

Continuation therapy - Medical necessity

Continuation requests for Tegsedi (inotersen) may be approved if the following criteria are met:

ALL of the following

Individual has a diagnosis of polyneuropathy of hereditary transthyretin (hATTR) amyloidosis
Documentation is provided that individual has a TTR mutation verified by genotyping (Benson 2018)
Documentation is provided to show clinically significant improvement or stabilization in clinical signs and symptoms of disease (including but not limited to improved ambulation, improvement in neurologic symptom burden, improvement in activities of daily living)
Individual's most recent platelet count was within the past month and was greater than or equal to 100 x 10^9 /L>= 100 x 10^9 /L
Platelet count must be within past month

Not approved / Exclusions

Requests for Tegsedi (inotersen) may not be approved for the following:

ANY of the following

Individual has a history of liver transplantation
Individual has a history of acute glomerulonephritis caused by Tegsedi
Individual has New York Heart Association (NYHA) class III or IV heart failure (Benson, 2018)
Individual has sensorimotor or autonomic neuropathy not related to hATTR amyloidosis (monoclonal gammopathy, autoimmune disease, etc.) (Benson, 2018)
Individual is using in combination with Amvuttra, Attruby, Onpattro, Vyndaqel, Vyndamax, or Wainua

Applicable Codes

HCPCS for TegsediHCPCS

C9399	Unclassified drugs or biologicals [when specified as Tegsedi]
J3490	Unclassified drugs [when specified as Tegsedi (inotersen)]

ICD-10 Diagnosis (primary indication)ICD-10Covered

E85.1

Neuropathic heredofamilial amyloidosis [transthyretin-related (ATTR) familial amyloid polyneuropathy]

Provider Actions and Billing

Prior Authorization

Prior authorization required with clinical documentation

Initial and continuation requests require prior authorization with clinical documentation including diagnosis of hATTR amyloidosis, genotyping-confirmed TTR mutation, polyneuropathy status, baseline and recent laboratory results (platelet count and UPCR), and for continuation requests evidence of clinical improvement or stabilization.

Required documentation: diagnosis of hATTR amyloidosis (E85.1)
TTR mutation confirmed by genotyping
Documentation of polyneuropathy status (mild to moderate polyneuropathy)
Baseline and recent platelet count and UPCR
For continuation: evidence of clinical improvement or stabilization

Documentation Required

Clinical Evidence

-19.7mNIS+7 difference vs placebo at week 66 (95% CI -26.4 to -13.0)

-11.7Norfolk QOL‑DN difference vs placebo at week 66 (95% CI -18.3 to -5.1)

Safety summary: Tegsedi carries boxed warnings for thrombocytopenia and glomerulonephritis, and causes reductions in serum vitamin A (vitamin A supplementation recommended). Pivotal trials enrolled ambulatory adults with stage 1–2 disease (NIS 10–130) and required TTR genotyping plus biopsy-confirmed amyloid as entry criteria.

Background & Definitions

Background: Tegsedi (inotersen) is an FDA-approved antisense oligonucleotide for polyneuropathy in hATTR amyloidosis. Clinical trials demonstrated benefit in ambulatory patients with stage 1–2 disease (NIS 10–130) and required TTR genotyping and biopsy-proven amyloid. Major safety warnings include boxed thrombocytopenia and glomerulonephritis, monitoring requirements for platelets, UPCR, serum creatinine and eGFR, and recommendation for REMS enrollment. The manufacturer has discontinued Tegsedi; criteria will remain active until September 2026 to allow claims adjudication.

Definitions

hATTR amyloidosisHereditary transthyretin-mediated amyloidosis, formerly familial amyloid polyneuropathy (FAP); a progressive multisystem disease caused by extracellular deposition of misfolded transthyretin (TTR) amyloid fibrils leading to polyneuropathy, cardiomyopathy and multisystem involvement.

UPCRUrinary protein to creatinine ratio; used to screen for renal safety on Tegsedi. Tegsedi should not be initiated if UPCR is greater than or equal to 1000 mg/g and UPCR should be monitored at baseline and every two weeks during treatment.

NISNeuropathy Impairment Score; a clinical assessment used to quantify neuropathy burden (trial entry example: NIS 10–130 on a scale of 0–244).

Revision History

08/15/2025revisedLatest

Annual Review (material): Clinical and coding changes to continuation criteria and combination-exclusion list; removed renal and hepatic exclusions; added Attruby to may-not-use-in-combination criteria; administrative update to add documentation; coding reviewed — removed ICD-10-CM E85.2-E85.9 and G62.9 and updated HCPCS C9399 and J3490 descriptions. (is_material)

08/16/2024revised

Annual Review (material): Added Wainua to may-not-use-in-combination criteria; coding reviewed with no changes. (is_material)

08/21/2020added

Policy Summary

PayerAnthem

PolicyMedical Drug Clinical Criteria - Tegsedi (inotersen)

Policy CodePolicy CC-0084

Change TypeRevised (clinical & coding updates)

Effective DateOct 1, 2025

Next Review Date

SourceLink

On This Page

Individual's most recent urinary protein to creatinine ratio (UPCR) was within the past month and was less than 1000 mg/gUPCR < 1000 mg/g

UPCR must be within past month

May not be approved when the above criteria are not met and for all other indications

Laboratory monitoring and documentation

Obtain and document baseline platelet count and UPCR prior to initiation. During treatment, monitor platelet counts weekly if values are ≥ 75 x 10^9/L and more frequently if values are < 75 x 10^9/L. Monitor serum creatinine, eGFR and UPCR at baseline and every two weeks during treatment. Following discontinuation, monitor platelet counts for at least 8 weeks.

Baseline: platelet count and UPCR prior to initiation
Platelet monitoring cadence: weekly if ≥ 75 x 10^9/L; more frequently if < 75 x 10^9/L
Serum creatinine, eGFR and UPCR: baseline and every two weeks during treatment
Post-discontinuation: monitor platelets for at least 8 weeks

Billing Rule

Quantity limit

Tegsedi (inotersen) 284 mg/1.5 mL prefilled syringe has a quantity limit of 4 syringes per 28 days.

Tegsedi 284 mg/1.5 mL prefilled syringe quantity limit = 4 syringes per 28 days; HCPCS: C9399, J3490

Denial Risk

Contraindication and denial conditions

Requests may be denied for specified contraindications and conditions.

Baseline platelet count < 100 x 10^9/L (contraindicated)
UPCR ≥ 1000 mg/g
History of liver transplantation
Prior Tegsedi-induced acute glomerulonephritis
New York Heart Association (NYHA) class III or IV heart failure
Sensorimotor or autonomic neuropathy not related to hATTR amyloidosis (non-hATTR neuropathy)
Concomitant use with Amvuttra, Attruby, Onpattro, Vyndaqel, Vyndamax, or Wainua

Documentation Required

REMS enrollment

Prescribers must enroll in the Tegsedi REMS Program and follow required risk management procedures per the manufacturer and FDA.

Annual Review (material): Introduced continuation criteria to Tegsedi clinical criteria and added drug-specific quantity limit (Tegsedi 284 mg/1.5 mL prefilled syringe limit = 4 syringes per 28 days). (is_material)