Table 1.
FDA- and/or European Medicines Agency-approved RNA therapies.
| Treatment | Type | Amendment & Product Delivery | Mode of Delivery | Destination Site | Disease | Target Gene and Route | FDA and/or EMA Approval Year |
|---|---|---|---|---|---|---|---|
| Lumasiran (Oxlumo, ALN-GO1) | 21 nt ds-siRNA | 2nd gen; 2′-F/2′-O-Me; GalNAc-conjugated. | Subcutaneous | Liver | Primary hyperoxaluria type 1 | Hydroxyacid oxidase-1 (HAO1) mRNA | 2020 (EMA), 2020 (FDA) |
| Inclisiran (Leqvio, ALN-PCSsc) | 21 nt ds-siRNA | 2nd gen; 2′-F/2′-O-Me; GalNAc-conjugated. | Subcutaneous | Liver | Atherosclerotic cardiovascular disease, elevated cholesterol, homozygous/heterozygous familial hypercholesterolaemia | Proprotein convertase subtilisin/kexin type 9 (PCSK9) mRNA | 2020 (EMA) |
| Volanesorsen (Waylivra) | 20-mer ASO | 2nd gen; 2′-MOE gapme | Subcutaneous | Liver | Familial chylomicronaemia syndrome | Apolipoprotein CIII (APOC3) mRNA | 2019 (EMA) |
| Viltolarsen (Viltepso, NS-065, NCNP-01) | 21-mer ASO | 3rd gen; 2′-MOE PMO | Intravenous | Muscle | Duchenne muscular dystrophy | DMD pre-mRNA splicing (exon 53 skipping) | 2020 (FDA) |
| Givosiran (Givlaari) | 21 nt ds-siRNA | 2nd gen; 2′-F/2′-O-Me; GalNAc-conjugated | Subcutaneous | Liver | Acute hepatic porphyria | Delta aminolevulinic acid synthase 1 (ALAS1) mRNA | 2020 (EMA), 2019 (FDA) |
| Golodirsen (Vyondys 53, SRP-4053) | 25-mer ASO | 3rd gen; 2′-MOE PMO | Intravenous | Muscle | Duchenne muscular dystrophy | DMD pre-mRNA splicing (exon 53 skipping) | 2019 (FDA) |
| Patisiran (Onpattro) | 21 nt ds-siRNA | 2nd gen; 2′-F/2′-O-Me; liposomal | Intravenous | Liver | Hereditary transthyretin amyloidosis | Transthyretin (TTR) mRNA | 2018 (EMA), 2019 (FDA) |
| Inotersen (Tegsedi, AKCEA-TTR-LRx) | 20-mer ASO | 2nd gen; 2′-MOE; GalNAc-conjugated | Subcutaneous | Liver | Hereditary transthyretin amyloidosis | Transthyretin (TTR) mRNA | 2018 (EMA), 2018 (FDA) |
| Eteplirsen (Exondys 51) | 30-mer ASO | 3rd gen; 2′-MOE PMO | Intravenous | Muscle | Duchenne muscular dystrophy | Dystrophin (DMD) pre-mRNA splicing (exon 51 skipping) | 2016 (FDA) |
| Nusinersen (Spinraza, ASO-10-27) | 18-mer ASO | 2nd gen; 2′-MOE | Intrathecal | Central nervous system | Spinal muscular atrophy | Survival of motor neuron 2 (SMN2) pre-mRNA splicing (exon 7 inclusion) | 2017 (EMA), 2016 (FDA) |
| Mipomersen (Kynamro) | 20-mer ASO | 2nd gen; 2′-MOE gapmer | Subcutaneous | Liver | Homozygous familial hypercholesterolaemia | Apolipoprotein B mRNA | 2012 (EMA), 2013 (FDA) |
| Fomivirsen (Vitravene) | 21-mer ASO | 1st gen; PT | Intravitreal | Eye | Cytomegalovirus (CMV) retinitis in immunocompromised patients | CMV IE-2 mRNA | 1998 (FDA), 1999 (EMA) * |
This document lists RNA therapeutics that have been approved by the FDA and/or the European Medicines Agency. Drugs are listed from the most recent approval. ASO, antisense oligonucleotide; ds, double-stranded; GalNAc, N-acetylgalactosamine; gen, generation; PMO, phosphoroamidate morpholino oligomer; PT, phosphothiorate; siRNA, small interfering RNA. * Due to the development of effective antiretroviral therapies, marketing was discontinued in 2002.