Treatment of Hereditary Amyloidosis

Policy ID: I-9201-001

Section: Injections

Effective Date: July 01, 2024

Last Reviewed: May 14, 2024

Applies To: Commercial Only

Description

Patisiran (Onpattro ^TM ) is a RNA interference (RNAi) therapeutic targeting transthyretin for the treatment of hereditary transthyretin amyloidosis (TTR amyloidosis, hATTR or ATTR). RNAi is a cellular process of gene silencing. Patisiran (Onpattro) silences specific messenger RNA, blocking the production of transthyretin protein. This enables the clearance of TTR amyloid deposits from and restores function in peripheral tissues.

Inotersen (Tegsedi ^TM ) is an antisense oligonucleotide (ASO) inhibitor of human transthyretin (TTR) protein synthesis indicated for the treatment of hereditary transthyretin amyloidosis (TTR amyloidosis, hATTR or ATTR). Inotersen (Tegsedi) causes degradation of mutant and wild-type TTR mRNA through binding to the TTR mRNA, which results in a reduction of serum TTR protein and TTR protein deposits in tissues.

Vutrisiran (Amvuttra™) is a transthyretin-directed small interfering RNA for the treatment of heredity transthyretin amyloidosis (TTR amyloidosis, hATTR or ATTR) associated polyneuropathy.

Treatment with patisiran (Onpattro), inotersen (Tegsedi), or vutrisiran (Amvuttra) typically leads to a decrease in serum vitamin A levels. Supplementation at the recommended daily allowance of vitamin A is advised for individuals. Higher doses than the recommended daily allowance should not be given to try to achieve normal serum vitamin A levels during treatment, as serum vitamin A levels do not reflect the total vitamin A in the body. Individuals should be referred to an ophthalmologist if they develop ocular symptoms suggestive of vitamin A deficiency (e.g., night blindness).

Hereditary transthyretin amyloidosis is a slowly progressive condition characterized by the buildup of abnormal deposits of amyloid protein in the body's organs and tissues. It is caused by mutations in the TTR gene. The TTR gene provides instructions for producing a protein called transthyretin, which transports vitamin A and thyroxine throughout the body. Transthyretin is produced primarily in the liver. A small amount is produced in the choroid plexus of the brain and in the retina. In TTR amyloidosis, transthyretin builds up as amyloid fibrils in tissues (primarily liver), interfering with the normal function of these tissues. The ideal setting for evaluation of the individual with hereditary transthyretin amyloidosis is a multi-disciplinary Amyloid Program.

Note: Onpattro is an intravenous infusion and may be covered under the medical benefit. Amvuttra is a healthcare administered subcutaneous injection and may be covered under the medical benefit. Tegsedi is a subcutaneous injection and may be covered under the pharmacy benefit.

Policy Application

All claims submitted for this policy will be processed according to the policy effective date and associated revision effective dates in effect on the date of service.

Criteria

Coverage is subject to the specific terms of the member's benefit plan.

Federal Employee Program members (FEP) should check with their Retail Pharmacy Program to determine if prior approval is required by calling the Retail Pharmacy Program at 1-800-624-5060 (TTY: 1-800-624-5077). FEP members can also obtain the list through the www.fepblue.org website.

Patisiran (Onpattro) or vutrisiran (Amvuttra) may be approved when ALL of the following are met:

The individual has ONE of the following:
- ALL of the following:
  - A diagnosis of polyneuropathy of hereditary transthyretin-mediated amyloidosis confirmed by testing (e.g., genetic testing, biopsy) AND
  - The requested agent is FDA approved for use in polyneuropathy of hereditary transthyretin-mediated amyloidosis AND
  - The individual has clinical manifestations of polyneuropathy (e.g., neuropathic pain, altered sensation, numbness, tingling, impaired balance, motor disability) OR
- The individual has another FDA approved indication for the requested agent and route of administration AND
If the individual has an FDA approved indication, then ONE of the following:
- The individual's age is within FDA labeling for the requested indication for the requested agent OR
- The prescriber has provided information in support of using the requested agent for the individual's age for the requested indication AND
The individual has NOT received a liver transplant AND
The prescriber is a specialist in the area of the individual's diagnosis (e.g., geneticist, neurologist) or the prescriber has consulted with a specialist in the area of the individual's diagnosis AND
The individual will NOT be using the requested agent in combination with another agent targeted in this program OR Vyndaqel (tafamidis meglumine) or Vyndamax (tafamidis) for the requested indication AND
The individual does NOT have any FDA labeled contraindications to the requested agent AND
The requested quantity (dose) is within FDA labeled dosing for the requested indication.

Reauthorization Criteria

Patisiran (Onpattro) or vutrisiran (Amvuttra) may be approved when ALL of the following are met:

The individual has been previously approved for the requested agent through Blue Cross Blue Shield of North Dakota's Medical Drug Review process AND
The individual has had clinical benefit with the requested agent AND
The prescriber is a specialist in the area of the individual's diagnosis (e.g., geneticist, neurologist) or the prescriber has consulted with a specialist in the area of the individual's diagnosis AND
The individual has NOT received a liver transplant AND
The individual will NOT be using the requested agent in combination with another agent targeted in this program OR Vyndaqel (tafamidis meglumine) or Vyndamax (tafamidis) for the requested indication AND
The individual does NOT have any FDA labeled contraindications to the requested agent AND
The requested quantity (dose) is within FDA labeled dosing for the requested indication.

The use of patisiran (Onpattro) and vutrisiran (Amvuttra) for all other indications not listed in this policy is considered experimental/investigational and therefore non-covered because the safety and/or effectiveness cannot be established by the available published peer-reviewed literature.

Procedure Codes

J0222

J0225

NOTE: In addition to the above criteria, product specific dosage and/or frequency limits may apply in accordance with the United States Food and Drug Administration (U.S. FDA)-approved product prescribing information, national compendia, Centers for Medicare and Medicaid Services (CMS) and other peer reviewed resources or evidence-based guidelines.

Diagnosis Code

E85.1

Professional Statements and Societal Positions Guidelines

Not Applicable

ND Committee Review

Internal Medical Policy Committee 5-14-2024 Effective July 01, 2024

Adopted precertification policy replacing I-201 same title effective 7/1/2024

Links

References (PDF)

Disclaimer

Current medical policy is to be used in determining a Member's contract benefits on the date that services are rendered. Contract language, including definitions and specific inclusions/exclusions, as well as state and federal law, must be considered in determining eligibility for coverage. Members must consult their applicable benefit plans or contact a Member Services representative for specific coverage information. Likewise, medical policy, which addresses the issue(s) in any specific case, should be considered before utilizing medical opinion in adjudication. Medical technology is constantly evolving, and the Company reserves the right to review and update medical policy periodically.

Policy ID: I-201-010

Section: Injections

Effective Date: July 15, 2019

Revised Date: May 08, 2024

Revision Effective Date: June 30, 2024

Last Reviewed: May 14, 2024

Archived Date: June 30, 2024

Applies To: Commercial Only

Description

Patisiran (Onpattro^TM) is a RNA interference (RNAi) therapeutic targeting transthyretin for the treatment of hereditary transthyretin amyloidosis (TTR amyloidosis, hATTR or ATTR). RNAi is a cellular process of gene silencing. Patisiran (Onpattro) silences specific messenger RNA, blocking the production of transthyretin protein. This enables the clearance of TTR amyloid deposits from and restores function in peripheral tissues.

Inotersen (Tegsedi^TM) is an antisense oligonucleotide (ASO) inhibitor of human transthyretin (TTR) protein synthesis indicated for the treatment of hereditary transthyretin amyloidosis (TTR amyloidosis, hATTR or ATTR). Inotersen (Tegsedi) causes degradation of mutant and wild-type TTR mRNA through binding to the TTR mRNA, which results in a reduction of serum TTR protein and TTR protein deposits in tissues.

Vutrisiran (Amvuttra™) is a transthyretin-directed small interfering RNA for the treatment of heredity transthyretin amyloidosis (TTR amyloidosis, hATTR or ATTR) associated polyneuropathy.

Criteria

Coverage is subject to the specific terms of the member's benefit plan.

Patisiran (Onpattro) may be considered medically necessary for the treatment of individuals 18 years of age and older with a diagnosis of hereditary TTR amyloidosis when ALL of the following criteria are met:

Prescribed by or in consultation with a neurologist or physician who specializes in the treatment of amyloidosis; and
Diagnosis of polyneuropathy associate with hereditary TTR amyloidosis; and
Documented mutation in TTR gene as confirmed by genetic testing; and
A complete neurologic examination has been performed, showing clinical signs and symptoms of the disease (e.g., peripheral/autonomic neuropathy, motor disability, carpel tunnel, etc.) ; and
Patisiran (Onpattro) is not being used for sensorimotor or autonomic neuropathy unrelated to hATTR amyloidosis; and
Documentation of baseline functional ambulation performance (FAP) stage of 1 or 2; and
Has documentation of ANY of the following:
- Peripheral neuropathy impairment score (NIS) of five (5) or greater; or
- Polyneuropathy disability (PND) score of IIIb or lower; and
Has not had a prior liver transplant or scheduled liver transplant; and
Has adequate liver function (AST and ALT less than or equal to 2.5 times upper limit of normal, total bilirubin within normal limits and INR less than or equal to two (2)); and
Has adequate renal function (Serum Creatinine level less than or equal to two (2) times upper limit of normal or creatinine clearance greater than 30 mls/min); and
Individual is not simultaneously utilizing other gene targeted therapy for polyneuropathy of hATTR.

Reauthorization Criteria

Individual meets the above criteria; and
Individual has documentation of a positive clinical response to patisiran (Onpattro) (e.g., improved or stabilized neurologic impairment, motor function, quality of life assessment, serum TTR levels, etc.) as demonstrated by an improvement or stabilization in ANY of the following:
- NIS; or
- PND score; or
- FAP stage.

The use of patisiran (Onpattro) for all other indications not listed in this policy is considered experimental/investigational and therefore non-covered because the safety and/or effectiveness cannot be established by the available published peer-reviewed literature.

Procedure Code

J0222

Vutrisiran (Amvuttra) may be considered medically necessary for the treatment of individuals 18 years of age and older with a diagnosis of hereditary TTR amyloidosis when ALL of the following criteria are met:

Prescribed by or in consultation with a neurologist or physician who specializes in the treatment of amyloidosis; and
Diagnosis of polyneuropathy associate with hereditary TTR amyloidosis; and
Documented mutation in TTR gene as confirmed by genetic testing; and
A complete neurologic examination has been performed, showing clinical signs and symptoms of the disease (e.g., peripheral/autonomic neuropathy, motor disability, carpel tunnel, etc.) ; and
Vutrisiran (Amvuttra) is not being used for sensorimotor or autonomic neuropathy unrelated to hATTR amyloidosis; and
Documentation of baseline functional ambulation performance (FAP) stage of 1 or 2; and
Has documentation of ANY of the following:
- Peripheral neuropathy impairment score (NIS) of five (5) or greater; or
- Polyneuropathy disability (PND) score of IIIb or lower; and
Has not had a prior liver transplant or scheduled liver transplant; and
Individual has normal liver function tests; and
Individual is not simultaneously utilizing other gene targeted therapy for polyneuropathy of hATTR.

Reauthorization Criteria

Individual meets the above criteria; and
Individual has documentation of a positive clinical response to vutrisiran (Amvuttra) (e.g., improved or stabilized neurologic impairment, motor function, quality of life assessment, serum TTR levels, etc.) as demonstrated by an improvement or stabilization in ANY of the following:
- NIS; or
- PND score; or
- FAP stage.

The use of vutrisiran (Amvuttra) for all other indications not listed in this policy is considered experimental/investigational and therefore non-covered because the safety and/or effectiveness cannot be established by the available published peer-reviewed literature.

Procedure Code

J0225

Tegsedi (inotersen) is a subcutaneous injection and may be covered under the pharmacy benefit.

Diagnosis Code

E85.1

Professional Statements and Societal Positions Guidelines

Not Applicable

ND Committee Review

Internal Medical Policy Committee 7-16-2019 Onpattro and Tegsedi changed to precertification drugs

Internal Medical Policy Committee 5-19-2020 Annual review, no content change

Internal Medical Policy Committee 11-19-2020 Annual review, no content change

Internal Medical Policy Committee 11-23-2021 Annual review, no clinical content change

Internal Medical Policy Committee 5-24-2022 Updated the experimental/investigational statement

Internal Medical Policy Committee 9-28-2022 - Effective October 01, 2022

Added new drug, vutrisiran (Amvuttra), to the policy

Internal Medical Policy Committee 9-28-2022 - Effective January 01, 2023

Added new code, J0225, for vutrisiran (Amvuttra) to the policy
Updated experimental/investigational statement

Internal Medical Policy Committee 11-15-2023 Annual review, no clinical content change

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