Vyondys 53: which tox species, and why?

“The toxicity of golodirsen was assessed in adult male C57BL/6NCrl mouse and cynomolgus monkey and in male juvenile Sprague Dawley rat.”

“No in vivo nonclinical studies were conducted to assess the extent of exon 53 skipping by golodirsen.”

“These in vivo studies were conducted using a murine surrogate PMO, AVI-4225, in the mdx mouse, an animal model of DMD.”

“The toxicity of golodirsen was assessed in adult male C57BL/6NCrl mouse and cynomolgus monkey and in male juvenile Sprague Dawley rat.”

“No developmental and reproductive toxicity studies were conducted with golodirsen because the patient population is almost entirely male. Potential effects on male fertility were assessed by histopathological evaluation of male reproductive organs and sperm assessment in toxicity studies.”

“Administration of golodirsen to male transgenic (Tg.rasH2) mice (0, 100, 300, or 1000 mg/kg) weekly for 26 weeks by subcutaneous injection and to male rats (0, 30, 100, or 300 mg/kg) weekly for up to 102 weeks by intravenous injection resulted in no increase in neoplasms.”

“Proof of concept for the exon-skipping mechanism was demonstrated in studies originally submitted and reviewed under IND 77429 and NDA 206488 (EXONDYS). These in vivo studies were conducted using a murine surrogate PMO, AVI-4225, in the mdx mouse, an animal model of DMD.”