We reported new clinical data from our ongoing Phase 2 open-label extension (OLE) studies with patisiran and revusiran, investigational RNAi therapeutics targeting transthyretin (TTR) for the treatment of hereditary TTR-mediated amyloidosis (hATTR amyloidosis). These data were presented at the XV International Symposium on Amyloidosis held July 3 – 7, 2016 in Uppsala, Sweden.
Hereditary ATTR Amyloidosis with Cardiomyopathy (hATTR-CM)
ATTR amyloidosis is a progressive, life-threatening disease caused by misfolded transthyretin (TTR) proteins that accumulate as amyloid fibrils in multiple organs, but primarily in the peripheral nerves and heart. ATTR amyloidosis can lead to significant morbidity, disability, and mortality. TTR protein is produced primarily in the liver and is normally a carrier for retinol binding protein – one of the vehicles used to transport vitamin A around the body. Mutations in the TTR gene cause misfolding of the protein and the formation of amyloid fibrils that typically contain both mutant and wild-type TTR that deposit in tissues such as the peripheral nerves and heart, resulting in intractable peripheral sensory neuropathy, autonomic neuropathy, and/or cardiomyopathy.
Hereditary ATTR represents a major unmet medical need based on its significant morbidity and mortality. There are over 100 reported TTR mutations; the particular TTR mutation and the site of amyloid deposition determine the clinical manifestations of the disease, whether it is predominantly symptoms of neuropathy or cardiomyopathy.
Specifically, hereditary ATTR amyloidosis with cardiomyopathy (hATTR-CM), also referred to familial amyloidotic cardiomyopathy (FAC) is an inherited, progressive, life-threatening disease. It is due to a mutation in the transthyretin (TTR) gene, which causes misfolded TTR proteins to accumulate as amyloid fibrils primarily in the heart. Hereditary ATTR amyloidosis with cardiomyopathy can result in heart failure and death.
While the exact numbers are not known, it is estimated hATTR-CM, also known as FAC, affects at least 40,000 people worldwide. hATTR-CM is fatal within 2.5 to 5 years of diagnosis and treatment is currently limited to supportive care. Wild-type ATTR amyloidosis, also known as senile systemic amyloidosis (SSA), is a nonhereditary, progressive, life-threatening disease caused by misfolded transthyretin (TTR) proteins that accumulate as amyloid fibrils in the heart. Wild-type ATTR amyloidosis can cause cardiomyopathy and result in heart failure and death. There are no approved therapies for the treatment of hATTR-CM or SSA hence there is a significant unmet need for novel therapeutics to treat these patients.
Our hereditary ATTR program is the lead effort in our Genetic Medicine Strategic Therapeutic Area (STAr) product development and commercialization strategy, which is focused on advancing innovative RNAi therapeutics toward genetically defined targets for the treatment of rare diseases with high unmet medical need. We are developing revusiran (ALN-TTRsc), a subcutaneously administered RNAi therapeutic for the treatment of hATTR-CM.
Revusiran for the Treatment of hATTR-CM
Please read the latest press releases and data presentations for revusiran here.