Date: 2014-10-16
Type of information: Results
phase: 1
Announcement: results
Company: Sarepta Therapeutics (USA - MA)
Product: AVI-6003
Action
mechanism: AVI-6003 for the treatment of Marburg is a combination therapy of two PMOs, (AVI-7287 and AVI-7288), which target the viral proteins VP24 and NP, respectively.Results from previous viral challenge studies of AVI-6003 in non-human primates demonstrated prevention of disease development and death following exposure to Marburg virus. Subsequent animal studies demonstrated that only one oligomer contributed to efficacy, and therefore, the lead drug candidates for Marburg have since become the single compounds AVI-7288. PMOplus® chemistry is an advanced generation of Sarepta\'s phosphorodiamidate morpholino oligomer, or PMO, technology pioneered by Sarepta. The PMO platform is designed to provide a stable chemistry backbone with drug-like characteristics for Sarepta\'s advanced RNA-based therapeutics. PMOplus® chemistry includes specific molecular charges positionally inserted into the PMO\'s inherent charge-neutral backbone.
Disease: Marburg fever
Therapeutic area: Infectious diseases
Country:
Trial
details: The Phase I clinical study was a randomized, double-blind, placebo-controlled trial designed to characterize the safety, tolerability and pharmacokinetics of single doses of intravenous formulations of AVI-6003 in healthy adult volunteers. 30 subjects were enrolled in six cohorts receiving up to 9 mg/kg of the combination drug candidates (4 active:1 placebo per cohort) for a total of 60 subjects.
Latest
news: * On October 16, 2014, Sarepta Therapeutics, a developer of innovative RNA-based therapeutics, announced the publication of results from two single ascending-dose studies that demonstrated no clinical or toxicologic safety concerns with the company’s drug candidates for the treatment of Ebola and Marburg virus, respectively. AVI-6003 for the treatment of Marburg is a combination therapy of two PMOs, (AVI-7287 and AVI-7288), which target the viral proteins VP24 and NP, respectively. Subsequent animal studies demonstrated that only one oligomer contributed to efficacy, and therefore, the lead drug candidates for Ebola and Marburg have since become the single compounds AVI-7288. Results of the Phase I clinical study showed the compound to be well-tolerated with no dose limiting level demonstrated. No clinically significant or dose-dependent effects were observed at any of the safety endpoints evaluated. A previously reported Phase I MAD study of AVI-7288 for the treatment of Marburg found no clinically significant or dose-dependent effects on any of the safety endpoints evaluated when tested at up to 16 mg/kg/day for 14 days in healthy adult volunteers. The results of these clinical studies add to a growing body of evidence supporting the safety of Sarepta’s PMO-based chemistry platform across a broad range of disease targets. This work was conducted under contract with the Joint Product Management Office of BioDefense Therapeutics (BD-Tx). The study results are to be published in the November issue of the American Society for Microbiology’s journal, Antimicrobial Agents and Chemotherapy and are available online at dx.doi.org/10.1128/AAC.03442-14.
