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 may be covered under the medical benefit. Tegsedi is a subcutaneous injection and may be covered under the pharmacy benefit.