Date: 2015-07-22
Type of information: Publication of results in a medical journal
phase: 1
Announcement: publication of results in The New English Journal of Medicine
Company: Sarepta Therapeutics (USA - MA)
Product: AVI-7288
Action
mechanism: antisense oligonucleotide. AVI-7288 is a phosphorodiamidate morpholino oligomer with positive charges that targets the viral messenger RNA that encodes Marburg virus (MARV) nucleoprotein. Its is designed to bind to viral RNA and inhibit the synthesis of the nucleocapsid protein (NP). NP supports the replication of the viral genetic material in an infected cell, and is also involved in the assembly of mature viruses. Inhibition of NP is intended to interrupt the viral lifecycle and stop or slow the spread of the disease to other cells in the body. AVI-7288 utilizes Sarepta’s advanced and proprietary PMOplus® technology. This mechanism of AVI-7288 is fundamentally distinct from other RNA-based anti-infective therapies that utilize a gene editing or degradation pathway.
Disease: Marburg Virus (MARV) infection
Therapeutic area: Infectious diseases
Country: USA
Trial
details: The Phase I clinical study was a randomized, double-blind, placebo-controlled trial designed to characterize the safety, tolerability and pharmacokinetics of AVI-7288 after daily repeat dosing. Over 14 days, 40 healthy human volunteers (8 per dose group) were dosed with up to 16 mg/kg/day, representing the highest continuous dosing of any PMOplus® or any other antisense oligonucleotide. This dosing also exceeded the predicted human efficacious dose for AVI-7288 estimated by three different models based upon nonhuman primate studies demonstrating up to 100% animal survival, including in a delayed time to treat setting. (NCT01566877)
Latest
news: * On July 22, 2015, Sarepta Therapeutics announced the publication of results from a multiple ascending dose study to determine the safety of AVI-7288, a PMOplus® antisense oligonucleotide, in healthy adult volunteers, in the July 23, 2015 issue of the New England Jounal of Medicine. The results of the study, conducted in collaboration with the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), demonstrated no clinical or toxicologic safety concerns with AVI-7288, an investigational treatment for Marburg Virus (MARV) infection. These results add to the continued documentation of safety data for Sarepta’s PMO-based technology. In healthy human volunteers, no significant safety concerns or dose-dependent adverse side effects of AVI-7288 were reported with respect to any safety end point evaluated, nor were any gross abnormalities in renal function or biomarkers of renal dysfunction observed. The maximum dose of AVI-7288 that could be administered without raising significant safety concerns was not reached. This work was conducted under contract with the Department of Defense Medical Countermeasures Systems/Joint Product Management Office of BioDefense Therapeutics (BD-Tx).
