Page 56 - ITPS-7-3

INNOSC Theranostics and
Pharmacological Sciences Designing miRNA ONTs for cardiometabolic pandemics

Table 2. Oligonucleotide therapeutics approved by regulatory authorities
Year of Compound Category Chemical changes Coupling agent Route of Indication
approval (Trade name) administration
1998 Fomivirsen 21-mer ASO PS, DNA - Intravitreal CMV retinitis
(VITRAVENE )
®
2004 Pegaptanib 27-mer Aptamer 2’-OH, 2’-F, 2’-OMe, PEG Intravitreal Neovascular AMD
®
(MACUGEN ) DNA
5
2013 Mipomersen 20-gapmer ASO PS, 2’-MOE, m C - Subcutaneous Hypercholesterolemia
(KYNAMRO )
®
2016 Eteplirsen 30-mer SSO 2’MOE, PMO - Intra-venous Duchenne muscular
®
(EXONDYS 51 ) dystrophy
2016 Nusinersen 18-mer SSO PS, 2’-MOE, m C - Intrathecal Spinal muscular atrophy
5
(SPINRAZA )
®
2018 Patisiran 21-mer/21-mer siRNA 2’-OH, 2’-OMe Liposomal Intravenous Hereditary transthyretin
(ONPATTRO ) amyloidosis (ATTR
®
amyloidosis)
2018 Inotersen 20-gapmer ASO PS, 2’-MOE, m C - Subcutaneous Hereditary ATTR
5
®
(TEGSEDI ) amyloidosis
2019 Givosiran 21-mer/23-mer siRNA PS, 2’-OMe, 2’-F 3 GalNAc residues Intravenous Acute hepatic porphyria
(GIVLAARI )
®
2019 Golodirsen 25-mer SSO 2’-MOE, PMO - Intravenous Duchenne muscular
(VYONDUS 53 ) dystrophy
®
2019 Volanesorsen 20-gapmer ASO PS, 2’-MOE m C - Subcutaneous Familial
5
(WAYLIVRA ) chylomicronemia
®
syndrome
2020 Lumasiran 21-mer/23-mer siRNA PS, 2’-OMe, 2’-F 3 GalNAc residues Subcutaneous Primary hyperoxaluria
(OXLUMO )
®
2020 Inclisiran 21-mer/23-mer siRNA PS, 2’-OMe, 2’-F 3 GalNAc residues Subcutaneous Hyper cholesterolemia
(LEQVIO )
®
2020 Viltolarsen 21-mer SSO 2’-OMe, PMO - Intravenous Duchenne muscular
(VILTEPSO ) dystrophy
®
2021 Casimersen 22-mer SSO PMO - Intravenous Duchenne muscular
(AMONDYS 45 ) dystrophy
®
2022 Vultrisiran 21-mer/23-mer siRNA PS, 2’-F, 2’-OMe 3 GalNAc residues Subcutaneous Hereditary ATTR
(AMVUTTRA ) amyloidosis
®
5
2023 Eplontersen 20-gapmer ASO PS, 2’-MOE, m C 1 trivalent Subcutaneous Transthyretin-mediated
(WAINUA ) GalNAc residue amyloidosis
®
2023 Nedosiran 22-mer/36-mer siRNA PS, 2’-F, 2’-OMe 4 GalNAc residues Subcutaneous Primary hyperoxaluria
®
(RIVFLOZA )
2023 Tofersen 20-gapmer ASO PS, 2’-MOE, m C - Intrathecal Amyotrophic lateral
5
(QALSODY ) sclerosis with
®
superoxide dismutase
(SOD1) gene
mutation
2023 Avacincaptad pegol 39-mer RNA Aptamer 2’-OMe, 2 PEG chains Intravitreal Age-related macular
(IZERVAY ) 2’-F, inverted degeneration
®
thymidine to cap
3’ end
Abbreviations: ASO: Antisense oligonucleotide; AMD: Age-related macular degeneration; CMV: Cytomegalovirus; GalNAc: N-acetyl-D-galactosamine;
m C: Cytosine methylated at position 5; PEG: Polyethylene glycol; PMO: Phosphorodiamidate morpholino oligomers; PS: Phosphorothioate;
5
siRNA: Small interfering RNA; SSO: Single stranded oligonucleotide; 2’-F: 2’-Fluoro; 2’-MOE: 2’-methoxyethyl; 2’-OH: 2’-hydroxyl;
2’-OMe: 2’-O-methyl; 2’-MOE: 2’-Methoxyethyl.
Volume 7 Issue 3 (2024) 3 doi: 10.36922/itps.3025