Eplontersen: First Approval

Abstract

Eplontersen (Wainua™) is a ligand-conjugated antisense oligonucleotide directed to TTR , which is being developed by Ionis Pharmaceuticals and AstraZeneca for the treatment of TTR-mediated amyloidosis (ATTR). Eplontersen, which is targeted to the liver by a ligand containing three N -acetyl galactosamine residues, binds to wild-type and variant TTR mRNA, thus reducing the levels of circulating TTR protein and amyloid deposition. Subcutaneous eplontersen reduced serum TTR levels, inhibited neuropathy progression and improved health-related quality of life in patients with polyneuropathy of hereditary ATTR (ATTRv-PN; v for variant) in a phase III trial. Based on these results, eplontersen was approved in the USA for the treatment of ATTRv-PN on 21 December 2023 and is currently undergoing regulatory review for a similar indication in the EU, the UK, Switzerland and Canada. Eplontersen is also undergoing phase III development for ATTR cardiomyopathy. This article summarizes the milestones in the development of eplontersen leading to this first approval for ATTRv-PN. Supplementary Information The online version contains supplementary material available at 10.1007/s40265-024-02008-5.

A Genome-wide CRISPR screen unveils the endosomal maturation protein WDR91 as a promoter of productive ASO activity in melanoma

“…ASOs are specially taken up by fast growing cells 3 and, among numerous advantages, bypass the current bottleneck regarding the targets that are considered undruggable with traditional small molecule inhibitors 4 . Several ASOs are currently approved by the Food and Drug Administration (FDA) for genetic and rare diseases 5,6 and several phase II and III studies are ongoing in the oncology therapeutic area 7 .…”