Amondys 45
casimersen · DMD exon 45 (PMO)Adult male mouse and cynomolgus monkey; juvenile male rat
Vitravene: which tox species, and why?
fomivirsen · CMV IE2 mRNA (ASO)
Species
Rabbit and monkey
“It appeared that intravitreal injection of ISIS 2922 caused cyclitis in the animals, monkeys and rabbits, and humans. The observed ocular changes were dose-dependent. In the severe cases, retina was involved in the ocular alterations.”
Why that species
No animal model of HCMV infection; antiviral activity shown only in vitro
“Due to lack of animal models for HCMV infection, the anti-CMV activity of fomivirsen has been demonstrated in in vitro tissue culture settings.”
Surrogate molecule
No surrogate; fomivirsen itself was injected intravitreally in rabbits and monkeys
“It appeared that intravitreal injection of ISIS 2922 caused cyclitis in the animals, monkeys and rabbits, and humans. The observed ocular changes were dose-dependent. In the severe cases, retina was involved in the ocular alterations.”
Species: general tox
Monkey and rabbit (intravitreal)
“It appeared that intravitreal injection of ISIS 2922 caused cyclitis in the animals, monkeys and rabbits, and humans.”
Species: DART
Not conducted: no reproductive toxicology information provided
“No information was provided.”
Species: carcinogenicity
Not conducted (waiver requested)
“A waiver from performing carcinogenicity studies was requested by the sponsor.”
Surrogate used in
No surrogate used; fomivirsen itself injected intravitreally in monkeys and rabbits
“It appeared that intravitreal injection of ISIS 2922 caused cyclitis in the animals, monkeys and rabbits, and humans.”
Same question, other oligonucleotides
Amvuttra
vutrisiran · TTR (siRNA)Rat and cynomolgus monkey (monkey only pharmacologically active; rat for off-target/class tox); rabbit EFD
Cyfendus
anthrax vaccine adsorbed, adjuvanted · TLR9 (CpG 7909 adjuvant)Rat only
Dawnzera
donidalorsen · Prekallikrein / KLKB1 (ASO)Mouse (CD-1) and cynomolgus monkey
Defitelio
defibrotide · Fragmented DNA oligonucleotidesRat and dog
Exondys 51
eteplirsen · DMD exon 51 (PMO)Cynomolgus monkey and juvenile rat (eteplirsen); mdx/C57BL mouse incl. mouse surrogate
Givlaari
givosiran · ALAS1 (siRNA)Rat and cynomolgus monkey (both pharmacologically active); rabbit inactive (EFD only)
Heplisav-B
hepatitis B vaccine (recombinant), adjuvanted · TLR9 (CpG 1018 adjuvant)Mouse, rat and cynomolgus monkey (repeat-dose); rabbit and baboon escalation studies
Izervay
avacincaptad pegol · C5 (aptamer)Rabbit and dog (IVT ocular studies); rat and cynomolgus monkey (7-day IV); monkey the only pharmacologically relevant species
Kynamro
mipomersen · APOB (ASO)Mouse, rat and cynomolgus monkey (clinical ASO plus rodent surrogates)
Leqvio
inclisiran · PCSK9 (siRNA)Rat and cynomolgus monkey (both pharmacologically active); rabbit for EFD
Macugen
pegaptanib · VEGF-165 (aptamer)Rabbit and dog (pivotal IVT); rat IV for systemic; supportive monkey, mouse
Onpattro
patisiran · TTR (siRNA)Rat and cynomolgus monkey (monkey pharmacologically active; rat off-target/LNP)
Oxlumo
lumasiran · HAO1 (siRNA)Rat and cynomolgus monkey (both pharmacologically relevant); rabbit for EFD
Qalsody
tofersen · SOD1 (ASO)Cynomolgus monkey (IT, relevant species), CD-1 mouse (SC) and rat single-dose IT
Qfitlia
fitusiran · Antithrombin / SERPINC1 (siRNA)Healthy rat and cynomolgus monkey (GLP); hemophilia A mouse, hemophilia A dog and induced-HA monkey models
Redemplo
plozasiran · APOC3 (siRNA)Rat (off-target toxicity) and cynomolgus monkey (pharmacologically relevant)
Rivfloza
nedosiran · LDHA (siRNA)Cynomolgus monkey (relevant) plus mouse (nedosiran inactive; off-target assessment)
Rytelo
imetelstat · Telomerase (oligo)Mouse and cynomolgus monkey (general tox); mouse and rabbit (EFD)
Spinraza
nusinersen · SMN2 (ASO)Juvenile cynomolgus monkey (IT) and CD-1 mouse (SC, systemic effects)
Tegsedi
inotersen · TTR (ASO)Mouse, rat and cynomolgus monkey; monkey the only pharmacologically relevant species
Tryngolza
olezarsen · APOC3 (ASO)Mouse (with surrogate) and cynomolgus monkey
Viltepso
viltolarsen · DMD exon 53 (PMO)Male CD-1 mouse and male cynomolgus monkey (plus juvenile male mouse)
Vyondys 53
golodirsen · DMD exon 53 (PMO)Mouse, cynomolgus monkey (adult males) and juvenile rat
Wainua
eplontersen · TTR (ASO)Mouse and cynomolgus monkey (monkey the pharmacologically relevant species)
Waylivra
volanesorsen · APOC3 (ASO)Mouse, rat and cynomolgus monkey (rabbit for embryo-fetal); monkey most relevant
Zanvastro
zilganersen · GFAP (ASO)Mouse (SC and ICV, juvenile) and juvenile monkey (intrathecal); mouse surrogate ASO arm