First-in-Class RNAi Treatment for Hereditary Transthyretin-Mediated Amyloidosis

Wednesday, August 15, 2018


The US Food and Drug Administration (FDA) has approved patisiran (Onpattro; Alnylam Pharmaceuticals, Cambridge, MA) for treatment of polyneuropathy in adults with hereditary transthyretin-mediated amyloidosis (hATTR). In this rare disease, abnormal amyloid deposits in the peripheral nerves result in polyneuropathy; cardiac function and ambulation are also affected and there is diminished quality of life.

Patisiran is the first interference-RNA based treatment to be approved by the FDA and represents another novel way of treating neurologic disease by affecting RNA transcription of a protein carrying a nonfunctional mutation. This is also the first treatment approved for patients with hATTR Patiseran is administered as an infusion of patisiran-filled lipid nanoparticles, delivering the iRNA directly to the liver. 

Approval was based upon a clinical trial that enrolled 225 patients, 148 of whom were randomly recived infusion of patisiran every 3 weeks over an 18-month period, and 77 of whom received placebo infusions at the same intervals. Those who received pattiseran had better outcomes on measures of polyneuropathy including muscle strength, sensation (pain, temperature, numbness), reflexes and autonomic symptoms (blood pressure, heart rate, digestion) compared to those receiving placebo. Patients treated with patisiran also scored better on assessments of walking, nutritional status and the ability to perform activities of daily living.

 "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. 

"There has been a long-standing need for a treatment for hereditary transthyretin-mediated amyloidosis polyneuropathy. This unique targeted therapy offers these patients an innovative treatment for their symptoms that directly affects the underlying basis of this disease," said Billy Dunn, MD, director of the Division of Neurology Products in the FDA's Center for Drug Evaluation and Research.

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