There are two types of ATTR amyloidosis: hereditary ATTR (hATTR) amyloidosis and wild-type ATTR (wtATTR) amyloidosis.
hATTR amyloidosis is a progressive, systemic, and fatal genetic disorder caused by the inappropriate formation and aggregation of TTR amyloid deposits in various tissues and organs throughout the body, including in peripheral nerves, heart, intestinal tract, eyes, kidneys, central nervous system, thyroid and bone marrow. Patients with hATTR amyloidosis often present with a mixed phenotype and experience overlapping symptoms of polyneuropathy and cardiomyopathy. The progressive accumulation of TTR amyloid deposits in these tissues and organs leads to sensory, motor and autonomic dysfunction often having debilitating effects on multiple aspects of a patient’s life.
Unfortunately, hATTR amyloidosis is often overlooked in the differential diagnosis, and accurate identification is unnecessarily delayed for years. Ultimately, hATTR amyloidosis results in death within three to fifteen years of symptom onset. Although the exact prevalence is difficult to determine, there are an estimated 50,000 patients with hATTR amyloidosis worldwide.
ATTR amyloidosis can also occur as a result of wild-type TTR protein misfolding and accumulating throughout the body, called wild-type ATTR (wtATTR) amyloidosis. There are an estimated 240,000 patients with wtATTR amyloidosis worldwide.
Therapeutic options for the treatment of patients with both forms of ATTR amyloidosis – hATTR and wtATTR – are limited, and there are currently no disease-modifying drugs approved in the U.S. for either form of the disease.
Akcea is developing two therapies for ATTR amyloidosis: inotersen and AKCEA-TTR-LRx. Inotersen is currently under regulatory review for marketing authorization in the U.S. and EU. AKCEA-TTR-LRx is planned to enter the clinic in 2018.