Viltepso: which tox species, and why?

“Repeat-dose studies in adult male CD1 mice, and single and repeat-dose studies in adult male cynomolgus monkeys were conducted to evaluate the general toxicology of vitolarsen.”

“In vivo assessment of exon 53 skipping was included in the 12- and 39-week toxicity studies in monkey; viltolarsen is not pharmacologically active in rodents.”

“In male mdx52 mice, IV administration of a mouse surrogate (NDK-73) as well as an additional morpholine oligonucleotide (NDK-33), which targets the Exon 53 3’ end of the mouse dystrophin gene”

“The pivotal IV toxicity studies were conducted in male CD-1 mouse (13 and 26 weeks) and male cynomolgus monkey (12 and 39 weeks).”

“Embryofetal development and pre- and postnatal development studies were not conducted, as agreed to by the Division, because of the intended patient population, which is almost exclusively male. A fertility and early embryonic development study was conducted in male CD-1 mice, which were mated with untreated females.”

“If the application is approved, a 26-week carcinogenicity study in Tg.rasH2 mouse and a 2-year carcinogenicity study in rat should be conducted as PMRs.”

“In male mdx52 mice, IV administration of a mouse surrogate (NDK-73) as well as an additional morpholine oligonucleotide (NDK-33), which targets the Exon 53 3’ end of the mouse dystrophin gene, resulted in 4.8% skipping efficiency in the gastrocnemius muscle 2 weeks after administration of 1280 mg/kg combination (640 mg/kg of each oligonucleotide).”