Amondys 45
casimersen · DMD exon 45 (PMO)Adult male mouse and cynomolgus monkey; juvenile male rat
Rytelo: which tox species, and why?
imetelstat · Telomerase (oligo)
Species
Mouse and cynomolgus monkey (general tox); mouse and rabbit (EFD)
“The mouse and monkey were used for the single- and repeat-dose toxicity studies, and mouse and rabbit were used for the EFD toxicity studies.”
Why that species
Sequence homology to hTR template region; 100% complementary in monkey, 9/13 mouse, 11/13 rat/rabbit
“These species were selected based on sequence homology to the template region of the RNA component of human telomerase and expected relevant pharmacologic action of imetelstat across species, from human to monkey to rabbit to rodent, as well as species-specific sensitivities to known ODN class effects.”
Surrogate molecule
No surrogate; clinical molecule tested in mouse, monkey and rabbit despite rodent mismatches
“Despite the mismatches, IC50 values are similar in tumour cell lines from all tested species, supporting their relevance for toxicology studies.”
Species: general tox
Mouse and monkey
“The mouse and monkey were used for the single- and repeat-dose toxicity studies, and mouse and rabbit were used for the EFD toxicity studies.”
Species: DART
Mouse and rabbit (EFD)
“The mouse and monkey were used for the single- and repeat-dose toxicity studies, and mouse and rabbit were used for the EFD toxicity studies.”
Species: carcinogenicity
Not conducted; mouse and rat carcinogenicity studies required as PMRs
“To address the carcinogenicity risk assessment of imetelstat, there will be separate Post Marketing Requirements (PMRs) for carcinogenicity assessments in the mouse and rat species.”
Surrogate used in
No surrogate used; clinical molecule active across tested species
“Despite the mismatches, IC50 values are similar in tumour cell lines from all tested species, supporting their relevance for toxicology studies.”
Same question, other oligonucleotides
Amvuttra
vutrisiran · TTR (siRNA)Rat and cynomolgus monkey (monkey only pharmacologically active; rat for off-target/class tox); rabbit EFD
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)
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)
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