Patisiran, an RNAi Therapeutic for the Treatment of Hereditary Transthyretin-Mediated Amyloidosis

Abstract

Hereditary transthyretin-mediated amyloidosis is a rapidly progressive, heterogeneous disease caused by the accumulation of misfolded transthyretin protein as amyloid fibrils at multiple sites, and is characterized by peripheral sensorimotor neuropathy, autonomic neuropathy and/or cardiomyopathy. Current treatment options have limited efficacy and often do not prevent disease progression. Patisiran is a novel RNA interference therapeutic that specifically reduces production of both wild-type and mutant transthyretin protein. In Phase II, III and long-term extension studies in patients with hereditary transthyretin-mediated amyloidosis, patisiran has consistently slowed or improved progression of neuropathy. In addition, the Phase III trial demonstrated significant improvements in quality of life measures and indicators of cardiomyopathy. Here, we highlight efficacy and safety data from the patisiran clinical trial programme.

Keywords: :

• cardiomyopathy
• clinical trials
• disease-modifying therapy
• hATTR amyloidosis
• patisiran
• polyneuropathy

Financial & competing interests disclosure

AV Kristen, S Ajroud-Driss, P Gorevic and T Kyriakides have nothing to disclose. I Conceição has received financial support as a primary investigator, serving on the scientific advisory board for Alnylam Pharmaceuticals, Ionis Pharmaceuticals and Pfizer. She also serves on the THAOS scientific advisory board. L Obici has received speaker fees and participated on scientific advisory boards for Alnylam Pharmaceuticals, Akcea and Pfizer. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

The authors received editorial support from Adelphi Communications Ltd, funded by Alnylam Pharmaceuticals.