Table 2.
FDA-approved oligonucleotides from 1998–2020.
| # | Active Ingredient (Trade Name) |
Company | Structure | Indication | Target | FDA Approval |
|---|---|---|---|---|---|---|
| 1 | Fomivirsen (VitraveneTM) |
Ionis Pharma (Carlsbad, CA, USA) Novartis (Basel, Switzerland) |
Antisense PS-ON a | Cytomegalovirus retinitis | CMV UL123 | August 1998 |
| 2 | Pegaptanib (MacugenTM) |
NeXstar Pharma (Boulder, CO, USA) Eyetech Pharma (Knolls, NJ, USA) |
Polynucleotide aptamer | Neovascular age-related macular degeneration | VEGF-165 | December 2004 |
| 3 | Mipomersen (KynamroTM) |
Ionis Pharma (Carlsbad, CA, USA) Genzyme (Cambridge, MA, USA) Kastle Tx (Housten, TX, USA) |
Antisense PS-ON a | Homozygous familial hypercholesterolaemia | APOB | January 2013 |
| 4 | Defibrotide (DefitelioTM) |
Jazz Pharma (Dublin, Ireland) |
Mixed single strands of DNA | Hepatic veno-occlusive disease | NA b | March 2016 |
| 5 | Eteplirsen (Exondys 51TM) |
Sarepta Tx (De Berry, TX, USA) |
Antisense PS-ON a/(PMO c) | Duchenne muscular dystrophy | DMD exon 51 | September 2016 |
| 6 | Nusinersen (SpinrazaTM) |
Ionis Pharma (Carlsbad, CA, USA) Biogen (Cambridge, MA, USA) |
Antisense PS-ON a/(PMO c) | Spinal muscular atrophy | SMN2 exon 7 | December 2016 |
| 7 | Patisiran (OnpattroTM) |
Alnylam Pharma (Cambridge, MA, USA) |
siRNA d | Hereditary transthyretin amyloidosis polyneuropathy | TTR | August 2018 |
| 8 | Inotersen (TegsediTM) |
Ionis Pharma (Carlsbad, CA, USA) Akcea Pharma (Boston, MA, USA) |
Antisense PS-ON a | Hereditary transthyretin; Amyloidosis polyneuropathy | TTR | October 2018 |
| 9 | Givosiran (GivlaariTM) |
Alnylam Pharma (Cambridge, MA, USA) |
siRNA d | Acute hepatic porphyria | Aminolevulinate synthase 1 (ALAS1) mRNA e | November 2019 (Enhanced) |
| 10 | Golodirsen (Vyondys 53TM) |
Sarepta Tx (De Berry, TX, USA) |
Antisense PMO c | Duchenne muscular dystrophy | DMD exon 53 | December 2019 |
| 11 | Viltolarsen (ViltepsoTM) | Nippon Shinyaku (Kisshoin, Minami-ku Kyoto) with (NCNP) f (Kodaira, Tokyo) |
Antisense PMO c | Duchenne muscular dystrophy | DMD exon 53 | August 2020 |
| 12 | Lumasiran (OxlumoTM) |
Alnylam Pharma (Cambridge, MA, USA) |
siRNA d | Primary hyperoxaluria type 1 (PH1) | HOA1 mRNA e | November 2020 |
a PS-ON: phosphorothioate oligonucleotide; b NA: not applicable, the mechanism of action is not well understood [3]; c PMO: phosphorodiamidate morpholino oligonucleotide; d siRNA: small interfering RNA; e mRNA: messenger RNA; f National Center of Neurology and Psychiatry.