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.

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.

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

·         Has documentation of ANY of the following:

o    Electrophysiologic test results indicative of polyneuropathy [eg nerve conduction study (NCS) and/or electromyography (EMG)]; or

o    Biopsy results indicative of polyneuropathy of hereditary TTR amyloidosis (eg. Amyloid deposits or large fiber involvement etc.); and

·         Documentation of baseline functional ambulation performance (FAP) stage of 1 or 2; and

·         Has documentation of ANY of the following:

o    Peripheral neuropathy impairment score (NIS) of five (5) greater; or

o    Polyneuropathy disability score of IIIb or lower; and

·         Has not had a prior 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.

Renewal 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 improvment or stabilization in ANY of the following:

o    Peripheral neuropathy impairment score (NIS); or

o    Polyneuropathy disability score; or

o    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.

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.