Amondys 45
casimersen · DMD exon 45 (PMO)Conducted; negative (Ames, CHO chromosomal aberration, mouse micronucleus)
Vyondys 53: genotox, carcinogenicity and repro: done or skipped?
golodirsen · DMD exon 53 (PMO)
Genotoxicity
Conducted; negative (Ames, CHO chromosomal aberration, mouse micronucleus)
“Golodirsen was negative in an adequately conducted standard battery of in vitro (Ames, chromosomal aberration in CHO cells) and in vivo (mouse bone marrow micronucleus) assays.”
Carcinogenicity
Not conducted pre-approval; dose-ranging done; Tg mouse and 2-year rat as PMRs
“No carcinogenicity studies have been conducted. The sponsor has conducted dose-ranging (DR) studies (reviewed below) to support planned carcinogenicity studies.”
Reproductive & developmental
Not conducted (almost exclusively male population); male reproductive assessments and juvenile rat study
“No developmental and reproductive toxicity studies were conducted with golodirsen because the patient population is almost entirely male.”
Safety pharmacology
Standalone telemetered monkey CV/CNS study (Latin square, up to 320 mg/kg IV) plus hERG; no effects
“In the only in vivo safety pharmacology study, golodirsen (0, 5, 40, or 320 mg/kg IV) had no effects on CNS, cardiovascular, or respiratory parameters in four male cynomolgus monkeys.”
Same question, other oligonucleotides
Amvuttra
vutrisiran · TTR (siRNA)Conducted: Ames, human lymphocyte chromosome aberration, rat micronucleus; all negative
Dawnzera
donidalorsen · Prekallikrein / KLKB1 (ASO)Conducted: in vitro Ames, CHL chromosomal aberration and in vivo mouse bone marrow micronucleus; no genotoxicity
Exondys 51
eteplirsen · DMD exon 51 (PMO)Conducted; negative (Ames, CHO chromosomal aberration, mouse micronucleus)
Givlaari
givosiran · ALAS1 (siRNA)Conducted: Ames, human lymphocyte chromosome aberration, rat micronucleus; all negative
Izervay
avacincaptad pegol · C5 (aptamer)Conducted: Ames, chromosomal aberration in mammalian cells, mouse micronucleus; all negative
Kynamro
mipomersen · APOB (ASO)Conducted; negative (Ames, mouse lymphoma, mouse micronucleus)
Leqvio
inclisiran · PCSK9 (siRNA)Conducted: standard panel, negative
Macugen
pegaptanib · VEGF-165 (aptamer)Conducted (GLP); pegaptanib and 2'-FU/2'-FC nucleosides negative overall
Onpattro
patisiran · TTR (siRNA)Conducted: Ames, human lymphocyte chromosome aberration, mouse micronucleus; all negative
Oxlumo
lumasiran · HAO1 (siRNA)Conducted: Ames, human lymphocyte chromosome aberration, rat micronucleus; all negative
Qalsody
tofersen · SOD1 (ASO)Conducted; negative (Ames, CHL chromosomal aberration, mouse micronucleus)
Qfitlia
fitusiran · Antithrombin / SERPINC1 (siRNA)Conducted: bacterial reverse mutation, in vitro chromosomal aberration (human lymphocytes), rat bone-marrow micronucleus; all negative
Redemplo
plozasiran · APOC3 (siRNA)Conducted: Ames, in vitro chromosomal aberration (TK6), in vivo mouse micronucleus; not genotoxic
Rivfloza
nedosiran · LDHA (siRNA)Conducted; negative (Ames, in vitro micronucleus, in vivo mouse micronucleus)
Rytelo
imetelstat · Telomerase (oligo)Conducted; negative (Ames, in vitro micronucleus, in vivo mouse micronucleus)
Spinraza
nusinersen · SMN2 (ASO)Conducted; negative (Ames, CHO chromosomal aberration, mouse micronucleus)
Tegsedi
inotersen · TTR (ASO)Conducted; negative (Ames, CHL chromosomal aberration, mouse micronucleus)
Tryngolza
olezarsen · APOC3 (ASO)Conducted; negative (Ames, chromosomal aberration, mouse micronucleus)
Viltepso
viltolarsen · DMD exon 53 (PMO)Conducted; negative (Ames, CHL chromosomal aberration, mouse micronucleus)
Wainua
eplontersen · TTR (ASO)Conducted; negative (Ames, chromosomal aberration, mouse micronucleus)
Waylivra
volanesorsen · APOC3 (ASO)Conducted: bacterial reverse mutation, mouse lymphoma TK, mouse bone-marrow micronucleus; all negative
Zanvastro
zilganersen · GFAP (ASO)Conducted: Ames, in vitro chromosomal aberration, mouse micronucleus; all negative