First-in-Class Therapy Approved for Polyneuropathy Caused by hATTR

Onpattro contains a transthyretin-directed small interfering RNA
Onpattro contains a transthyretin-directed small interfering RNA

The Food and Drug Administration (FDA) has approved Onpattro (patisiran; Alnylam) infusion for the treatment of polyneuropathy caused by hereditary transthyretin-mediated amyloidosis (hATTR) in adults.

Onpattro is a first-of-its-kind treatment in a class of drugs called small interfering ribonucleic acid (siRNA). This is the first FDA-approved therapy for this rare genetic disease. Polyneuropathy caused by hATTR results in the buildup of abnormal amyloid protein in peripheral nerves, the heart, and other organs. 

“This approval is part of a broader wave of advances that allow us to treat disease by actually targeting the root cause, enabling us to arrest or reverse a condition, rather than only being able to slow its progression or treat its symptoms. In this case, the effects of the disease cause a degeneration of the nerves, which can manifest in pain, weakness and loss of mobility,” said FDA Commissioner Scott Gottlieb, MD.

The mechanism of siRNAs consists of silencing a portion of RNA involved in causing the disease. Onpattro specifically encases the siRNA into a lipid nanoparticle to deliver the drug directly into the liver via an infusion; this changes or stops the production of disease-causing proteins. By preventing TTR production, Onpattro can help lower the accumulation of amyloid deposits in peripheral nerves, improving symptoms and disease management. 

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Onpattro was evaluated in a trial (N=225) where patients were randomized to receive Onpattro infusion once every 3 weeks for 18 months or placebo infusion. Patients in the Onpattro arm demonstrated better outcomes on measures of polyneuropathy, including muscle strength, sensation, reflexes, and autonomic symptoms vs patients in the placebo arm. In addition, Onpattro-treated patients performed better on assessments of walking, nutritional status, and ability to perform activities of daily living. 

Infusion-related reactions such as flushing, back pain, nausea, abdominal pain, dyspnea, and headache were the most common adverse effects reported. 

Onpattro will be available as a 10mg/5mL (2mg/mL) strength lipid complex injection in single-dose vials. 

For more information call (877) 265-9526 or visit FDA.gov.