There are two types of ATTR amyloidosis: hereditary ATTR (hATTR) amyloidosis and wild-type ATTR (wtATTR) amyloidosis.
Hereditary ATTR amyloidosis is an under-recognized, debilitating, and progressive disease. Hereditary ATTR amyloidosis is caused by the buildup of TTR proteins that misfold due to inherited mutations. It is the buildup of misfolded TTR protein that leads to amyloid fibril deposition in tissues and multiple organs throughout the body, including in peripheral nerves, heart, intestinal tract, eyes, kidneys, central nervous system, thyroid, and bone marrow. Patients with hereditary ATTR amyloidosis often present with symptoms of polyneuropathy or cardiomyopathy, or a mixed phenotype of both. The progressive accumulation of TTR amyloid deposits in tissues and organs leads to sensory, motor, and autonomic dysfunction, often having debilitating effects on multiple aspects of a patient’s life.
Unfortunately, hereditary ATTR amyloidosis is often overlooked in the differential diagnosis, and accurate identification is unnecessarily delayed for years. Ultimately, hereditary ATTR 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 hereditary ATTR 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 ATTR amyloidosis are limited.
TEGSEDI® (inotersen) is approved in the United States, Canada, and Europe for the treatment of polyneuropathy of hereditary ATTR amyloidosis. AKCEA-TTR-LRx is currently in clinical development for the treatment of ATTR.
- Prior to 2018 there were no approved treatments for this hereditary, progressive, and debilitating disease.
- Akcea initiated a phase 1/2 study of AKCEA-TTR-LRx to treat the broad population of patients with both hereditary and wild-type forms of ATTR amyloidosis.