RNA therapeutics on the rise
TABLE 1 | SELECTED RNA THERAPEUTICS APPROVED AND IN DEVELOPMENT
| Drug | Company | Indication | Status |
| ASO | |||
| Eteplirsen (Exondys 51) | Sarepta | DMD | Approved (2016)a |
| Nusinersen (Spinraza) | Ionis/Biogen | SMA | Approved (2016)a |
| Inotersen (Tegsedi) | Ionis/Akcea/PTC | hATTR | Approved (2018)a |
| Volanesorsen (Waylivra) | Ionis/Akcea/PTC | FCS | Approved (2019)b |
| Golodirsen (Vyondys 53) | Sarepta | DMD | Approved (2019)a |
| Viltolarsen | NS Pharma | DMD | NDA |
| Casimersen (SRP-4045) | Sarepta | DMD | NDA |
| TQJ230 (AKCEA-APO(a)-LRx) | Ionis/Akcea/Novartis | Hyperlipoproteinaemia with cardiovascular risk | Phase III |
| Tofersen | Ionis/Biogen | SOD1-driven ALS | Phase III |
| IONIS-HTTRx | Ionis/Roche | Huntington disease | Phase III |
| Trabedersen (OT-101) | Mateon (Oncotelic) | Brain cancer | Phase III |
| Volanesorsen | Ionis/Akcea | FPL | Phase III |
| siRNA | |||
| Patisiran (Onpattro) | Alnylam | hATTR | Approved (2018)a |
| Givosiran (Givlaari) | Alnylam | AHP | Approved (2019)a |
| Lumasiran | Alnylam | Hyperoxaluria | NDA |
| Inclisiran | Alnylam/Novartis (The Medicines Company) | Dyslipidaemia / hypercholesterolaemia | NDA |
| QR-110 | ProQR | Leber’s congenital amaurosis | Phase III |
| Vutrisiran | Alnylam | ATTR/hATTR | Phase III |
| QP-1002 | Quark | Renal disease/failure, Delayed graft function | Phase III |
| Tivanisiran (SYL1001) | Sylentis | Dry eye | Phase III |
| Fitusiran | Alnylam /Sanofi Genzyme | Haemophilia A and B | Phase III |
“RNA therapeutics have demonstrated most success in the treatment of rare diseases, especially neurological and hepatic diseases. Of the 21 late-stage RNA therapeutics, 18 have orphan status (Table 1). The most commercially successful drug to date has been nusinersen, which has $4.7 billion in sales up to the end of 2019 . The two currently approved siRNA drugs — patisiran (Onpattro; Alnylam) and givosiran (Givlaari; Alnylam) — target liver mRNAs for the treatment of hereditary transthyretin amyloidosis and acute hepatic porphyria, respectively. Patisiran achieved sales of more than $150 million in its first full year on the market in 2019, which are forecast to approximately double in 2020.”
Reference: RNA therapeutics on the rise, Nature review drug discovery, 27 APRIL 2020