Sarepta Therapeutics, Inc. today 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.
The studies were supported with funding by the DoD’s Joint Product Management Office of BioDefense Therapeutics (BD-Tx).
AVI-6002 for the treatment of Ebola is a combination therapy of two phosphorodiamidate morpholino oligomers (PMOs AVI-7537 and AVI-7539), which target the viral matrix proteins VP24 and VP35, 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.
The two Phase I clinical studies were randomized, double-blind, placebo-controlled trials designed to characterize the safety, tolerability and pharmacokinetics of single doses of intravenous formulations of AVI-6002 or AVI-6003 in healthy adult volunteers.
In each study, 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. Results showed the compounds 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. The safety and pharmacokinetics of the four compounds comprising the two combination therapies were similar, regardless of the target RNA sequence.
These drug candidates use Sarepta’s advanced and proprietary PMOplus® chemistry, which is also the basis of the company’s clinical-stage influenza drug candidate, AVI-7100. Results from previous viral challenge studies of AVI-6002 and AVI-6003 in non-human primates demonstrated prevention of disease development and death following exposure to Ebola or Marburg virus.
Subsequent animal studies demonstrated that for each combination therapy, only one oligomer contributed to efficacy, and therefore, the lead drug candidates for Ebola and Marburg have since become the single compounds AVI-7537 and AVI-7288.
“We believe these promising early clinical safety results, coupled with the strong safety and efficacy data generated from animal studies for all four PMO compounds, reinforce the use of our PMOplus chemistry platform to pursue potential treatments for deadly infectious diseases such as Ebola and Marburg,” said Michael Wong, senior medical director, infectious diseases at Sarepta Therapeutics. “We are particularly encouraged to see results such as these in the healthy human volunteers to what we have learned to be the effective agents, AVI-7537 and AVI-7288. These compounds have protected up to 80-100 percent of the non-human primates to Ebola and Marburg virus challenge infections, respectively.”
Read more on the study results at Antimicrobial Agents and Chemotherapy: Safety and Pharmacokinetic Profiles of Phosphorodiamidate Morpholino Oligomers with Activity against Ebola Virus and Marburg Virus: Results of Two Single-Ascending-Dose Studies.
Source: Sarepta press release, adapted.