Amondys 45
casimersen · DMD exon 45 (PMO)Adult male mouse and cynomolgus monkey; juvenile male rat
Dawnzera: which tox species, and why?
donidalorsen · Prekallikrein / KLKB1 (ASO)
Species
Mouse (CD-1) and cynomolgus monkey
“Mice and cynomolgus monkeys were considered suitable species for the pharmacology assessment because PKK is expressed in both species.”
Why that species
Donidalorsen inactive in mouse (no complementarity to mouse PKK transcript); monkey is pharmacologically relevant, mouse used with surrogate ASO
“Donidalorsen is not pharmacologically active in the mouse due to its lack of complementarity to the mouse PKK gene transcript.”
Surrogate molecule
Yes: mouse-specific surrogate ASO ISIS 482584 for pharmacology; ISIS 722059 mouse-active surrogate in 26-week mouse and repro studies
“ISIS 722059 (mouse-active surrogate) at 4 mg/kg/q2w was included in the 26-week mouse study.”
Species: general tox
CD-1 mouse and cynomolgus monkey
“repeat dose studies in CD-1 mice and cynomolgus monkeys of up to 26- and 39-week duration, respectively”
Species: DART
CD-1 mouse only (combined fertility/EFD and pre-/postnatal studies); no rabbit study
“Reproductive and developmental toxicity studies were conducted in one species only, namely CD-1 mice”
Species: carcinogenicity
Tg.rasH2 mouse (27-week, completed) and SD rat (2-year, ongoing)
“The carcinogenicity assessment for donidalorsen includes a completed 27-week study in Tg.rasH2 mice and a 2-year study in SD rats that is ongoing with the final report due in Q4 2025.”
Surrogate used in
Yes: mouse surrogate ISIS 722059 in mouse toxicity studies to assess on-target effects
“Donidalorsen does not align perfectly to the mouse PKK gene sequence, so the mouse toxicity studies also evaluated mouse surrogate ISIS 722059 to assess on-target effects.”
Same question, other oligonucleotides
Amvuttra
vutrisiran · TTR (siRNA)Rat and cynomolgus monkey (monkey only pharmacologically active; rat for off-target/class tox); rabbit EFD
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)
Hibsago
bepirovirsen · HBV RNA (ASO)Mouse and rabbit in labeled studies (carcinogenicity, reproduction); general-toxicity species not stated
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)
Vitravene
fomivirsen · CMV IE2 mRNA (ASO)Rabbit and monkey
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