Eplontersen (Wainua™) is a ligand-conjugated antisense oligonucleotide developed by Ionis Pharmaceuticals and AstraZeneca for the treatment of TTR-mediated amyloidosis (ATTR). It is targeted to the liver via a ligand containing three N-acetyl galactosamine residues, which allows it to bind to both wild-type and variant TTR mRNA, thereby reducing circulating TTR protein and amyloid deposition. In a phase III trial, 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). 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 the same indication in the EU, the UK, Switzerland, and Canada. Additionally, eplontersen is in phase III development for ATTR cardiomyopathy. This summary reflects the author's opinions. For a complete list of declarations, including funding and author disclosure statements, and copyright information, please refer to the full text online. © Springer Nature Switzerland AG 2024.Eplontersen (Wainua™) is a ligand-conjugated antisense oligonucleotide developed by Ionis Pharmaceuticals and AstraZeneca for the treatment of TTR-mediated amyloidosis (ATTR). It is targeted to the liver via a ligand containing three N-acetyl galactosamine residues, which allows it to bind to both wild-type and variant TTR mRNA, thereby reducing circulating TTR protein and amyloid deposition. In a phase III trial, 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). 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 the same indication in the EU, the UK, Switzerland, and Canada. Additionally, eplontersen is in phase III development for ATTR cardiomyopathy. This summary reflects the author's opinions. For a complete list of declarations, including funding and author disclosure statements, and copyright information, please refer to the full text online. © Springer Nature Switzerland AG 2024.