Our Member Services Representatives are unavailable Friday, April 10, due to the holiday.



Resources on COVID-19 and how BCBSND is responding to help protect all North Dakotans

Treatment of Hereditary Amyloidosis

Section: Injections
Effective Date: October 01, 2019
Revised Date: September 30, 2019


Patisiran (OnpattroTM) 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 (TegsediTM) 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.

Treatment with patisiran (Onpattro) or inotersen (Tegsedi) 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 (eg. 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 is covered under the medical benefit (review completed by BCBSND). Tegsedi is a subcutaneous injection and is covered under the pharmacy benefit (review completed by Prime under the hATTR Amyloidosis Neuropathy Prior Authorization Program).


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) 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 2); and
  • Has adequate renal function (Serum Creatinine level less than or equal to 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) is considered experimental/investigational and, therefore, non-covered for all other indications. Scientific literature does not support its use for other indications.

Procedure Code


Tegsedi is a subcutaneous injection and is covered under the pharmacy benefit (review completed by Prime under the hATTR Amyloidosis Neuropathy Prior Authorization Program).

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

Diagnosis Codes