Table 1.
List of Approved Oligonucleotide therapeutics
| Generic name | Type | Modification | Approval | Target | Indication | RoA |
|---|---|---|---|---|---|---|
| Fomivirsen | Antisense | PS | US 1998 EU 1999 |
CMV IE2 mRNA |
CMV retinitis | IVT |
| Pegaptanib | Aptamer (PEG) | 2′-F 2′-OMe |
US 2004 EU 2006 JP 2008 |
VEGF165 (protein) |
Neovascular ARMD | IVT |
| Mipomersen | Antisense (gapmer) | PS 2′-MOE |
US 2013 | ApoB-100 mRNA |
HoFH | SC |
| Eteplirsen | Antisense (SSO) | PMO | US 2016 | Dystrophin pre-mRNA |
DMD | IV |
| Nusinersen | Antisense (SSO) | PS 2′-MOE |
US 2016 EU 2017 JP 2017 |
SMN2 pre-mRNA |
Spinal muscular atrophy | IT |
| (CpG1018)1) | CpG oligomer | PS | US 2017 EU 2021 |
TLR9 (protein) |
HBV infection | IM |
| Inotersen | Antisense (gapmer) | PS 2′-MOE |
US 2018 EU 2018 |
TTR mRNA |
hATTR | SC |
| Patisiran | siRNA (LNP) | 2′-OMe | US 2018 EU 2018 JP 2019 |
TTR mRNA |
hATTR | IV |
| Volanesorsen | Antisense (gapmer) | PS 2′-MOE |
EU 2019 | ApoCIII mRNA |
FCS | SC |
| Givosiran | siRNA (GalNAc) | PS (partial) 2′-OMe; 2′-F |
US 2019 EU 2020 JP 2021 |
ALAS1 mRNA |
Acute hepatic porphyria | SC |
| Golodirsen | Antisense (SSO) | PMO | US 2019 | Dystrophin pre-mRNA |
DMD | IV |
| Viltolarsen | Antisense (SSO) | PMO | US 2020 JP 2020 |
Dystrophin pre-mRNA |
DMD | IV |
| Lumasiran | siRNA (GalNAc) | PS (partial) 2′-OMe; 2′-F |
US 2020 EU 2020 |
HAO1 mRNA |
PH1 | SC |
| Inclisiran | siRNA (GalNAc) | PS (partial) 2′-OMe; 2′-F |
EU 2020 US 2021 |
PCSK9 mRNA |
HeFH | SC |
| Casimersen | Antisense (SSO) | PMO | US 2021 | Dystrophin pre-mRNA |
DMD | IV |
| Vutrisiran | siRNA (GalNAc) | PS (partial) 2′-OMe; 2′-F |
US 2022 | TTR mRNA |
hATTR | SC |
1) CpG1018 is an oligonucleotide added as an adjuvant to the hepatitis B virus vaccine and is listed here as one type of oligonucleotide therapeutics.
ALAS1, delta-aminolevulinate synthase 1; ApoB, apolipoprotein B; ApoCIII, apolipoprotein CIII; ARMD, age-related macular degeneration; CMV, cytomegalovirus; DMD, Duchenne muscular dystrophy; EU, European Union; FCS, familial chylomicronemia syndrome; GalNAc, N-Acetylgalactosamine; hATTR, hereditary transthyretin amyloidosis; HAO1, hydroxyacid oxidase 1; HBV, hepatitis B virus; HeFH, heterozygous familial hypercholesterolemia; HoFH, homozygous familial hypercholesterolemia; IE2, immediate-early 2; IM, intramuscular; IT, intrathecal; IV, intravenous; IVT, intravitreal; JP, Japan; LNP, lipid nanoparticle; PCSK9, proprotein convertase subtilisin kexin 9; PEG, polyethylene glycol; PH1, primary hyperoxaluria type 1; RoA, route of administration; SC, subcutaneous; SMN2, survival motor neuron 2; TLR9, Toll-like receptor 9; TTR, transthyretin; US, United States; VEGF, vascular endothelial growth factor.