Table 1.

siRNA-based drugs in advanced clinical trials

S. no.	SiRNA drugs	Chemical modification	Delivery system/ targeting ligand	Targeting gene	Disease	Company	Phases
1	ONPATTRO (Patisiran)	2′-O-Me, dT	LNP-siRNA	TTR	TTR-mediated amyloidosis	Alnylam	Approved (2018)
2	GIVLAARI (Givosiran)	PS, 2′-O-Me, 2′-F	GalNAc-siRNA	ALAS1	Acute hepatic porphyria	Alnylam	Approved (2019)
3	OXLUMO (Lumasiran)	PS, 2′-O-Me, 2′-F	GalNAc-siRNA	HAO1	Primary hyperoxaluria type 1	Alnylam	Approved (2020)
4	LEQVIO (Inclisiran)	PS, 2′-F, 2′-O-Me, dT	GalNAc-siRNA	PCSK9	Hypercholesterolemia	Alnylam Novartis	Approved (2021)
5	Vutrisiran (ALN-TTRSC02)	PS, 2′-O-Me, 2′-F	GalNAc-siRNA	TTR	TTR-mediated amyloidosis	Alnylam	Phase III
6	Fitusiran (ALN-AT3SC)	PS, 2′-O-Me, 2′-F	GalNAc-siRNA	AT	Haemophilia A and B and rare blood disorders	Alnylam Sanofi Genzyme	Phase III
7	Nedosiran (DCR-PHXC)	PS, 2′-O-Me, 2′-F	GalNAc-siRNA	LDHA	Primary hyperoxaluria	Alnylam Dicerna	Phase III
8	Teprasiran (QPI-1002)	2′-O-Me	None	p53	Acute kidney injury	Quark Novartis	Phase III
9	Cosdosiran (QPI-1007)	2′-O-Me	None	Caspase 2	NAION and glaucoma	Quark	Phase III
10	Tivanisiran (SYL1001)	None	None	TRPV1	Ocular pain and dry eye disease	Sylentis	Phase III

abbreviations 2′-F, 2′-fluoro; 2′-O-Me, 2′-methoxy; 2′-O-MOE, 2’-methoxyethyl; dT, 2’-deoxythymidine; TTR, transthyretin; PS, phosphorothioate linkage; GalNAc, N-acetyl-D-galactosamine; TTR, Transthyretin; LNP, lipid nanoparticle; ALAS1, delta-aminolevulinate synthase 1; LDHA, lactate dehydrogenase A; HAO1, hydroxy acid oxidase 1; EU, European Union; PCSK9, proprotein convertase subtilisin/Kexin type 9; AT, antithrombin; TRPV1, transient receptor potential vanilloid 1; NAION, non-arteritic ischemic optic neuropathy; p53, tumor protein p53