Trabedersen

Trabedersen (1.4-50 nmol; intrathecal administration; single bolus dose; 5 nmol/h; intracerebral administration; continuous infusion; 1 week) is well tolerated in rabbits and cynomolgus monkeys at single intrathecal bolus doses up to 50 nmol, whereas continuous intracerebral infusion at a rate of 5 nmol/h for 1 week induces mild to moderate local leukocyte infiltration in rabbits^[1].
Trabedersen (30-1000 mg/kg; intravenous injection; single bolus dose) is well tolerated in mice and rats at single intravenous bolus doses up to 100 mg/kg, with an LD₅₀ value of 706 mg/kg in mice and 1175 mg/kg in rats^[1].
Continuous intravenous infusion of Trabedersen at a dose of 1 mg/kg/day is well tolerated in rats and monkeys, whereas continuous infusion at higher doses induces reversible inflammation and tissue damage; intravenous infusion at a dose of 8 mg/kg every other day for 4 weeks is also well tolerated in monkeys^[1].
In cynomolgus monkeys, trabedersen sodium (5-160 mg/kg; intravenous infusion; 2 h duration; single dose) is well tolerated at intravenous doses up to 20 mg/kg over a 2-hour infusion with respect to cardiovascular and complement activation endpoints; it is well tolerated at doses below 5 mg/kg with respect to hematological indices^[1].
Trabedersen (0.25-50 mg/kg; i.p.; three times per week; approximately 32-35 days) sodium exhibits potent dose-dependent antitumor activity in orthotopic xenograft melanoma mouse models, reduces lung metastasis, and shows evidence of immunomodulatory effects as well as cellular/nuclear uptake; among these, the 50/16 mg/kg dosing regimen significantly reduces the average tumor weight to 0.395 g^[2].
Trabedersen significantly reduces the tumor weight, tumor cell proliferation level, tumor vascularization degree, and incidence of lymph node metastasis of primary pancreatic cancer in orthotopic xenograft mouse models^[3].