What is the role of RNA-based therapies in the treatment of amyloidosis?

Updated: May 09, 2019
  • Author: Robert O Holmes, Jr, DO; Chief Editor: Herbert S Diamond, MD  more...
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Patisiran (Onpattro) was the first drug approved by the US Food and Drug Administration (FDA), in August 2018, for treatment of polyneuropathy caused by hereditary transthyretin-mediated amyloidosis (hATTR) in adults. The first of a new class of targeted RNA-based therapies, patisiran acts by using RNA to interfere with the production of mutant transthyretin (TTR) protein, thereby reducing serum TTR protein levels and TTR protein deposits in tissues. It is administered by intravenous (IV) infusion every 3 weeks.

Approval was based on the APOLLO clinical trial, in which patients taking patisiran (n=148) showed significantly improved scores on the Neuropathy Impairment Score+7 and Norfolk Quality of Life Questionnaire–Diabetic Neuropathy (QOL-DN) at 18 months, compared with those taking placebo (n=77) (P <  0.001). [100]


Inotersen (Tegsedi) was approved by the FDA in October 2018. Like patisiran, it is indicated for polyneuropathy of hATTR in adults; unlike patisiran, inotersen is given as a once-weekly subcutaneous injection that the patient or caregiver can administer. It is an antisense oligonucleotide that causes degradation of mutant and wild-type transthyretin mRNA by binding TTR mRNA. This action results in reduced TTR protein levels in serum and tissue.

Approval was based on a placebo-controlled trial in which.patients (n=172) were randomly assigned in a 2:1 ratio to receive weekly inotersen or placebo. Scores on the mNIS+7 and the QOL-DN showed improvement in those receiving inotersen (P <  0.001). [101]


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