Rare Disease Report

Sarepta's Ebola Drug Safe and Well Tolerated in Phase I Study

OCTOBER 17, 2014
James Radke

In the November issue of Antimicrobial Agents and Chemotherapy, Heald et al report on the safety and pharmacokinetic properties of combination phosphorodiamidate morpholino oligomers (PMOs) with activity against Ebola virus and Marburg virus in healthy volunteers. AVI-6002 and AVI-6003 are two combination drugs under evaluation for post-exposure prophylaxis of Ebola virus and Marburg virus, respectively.

Sarepta Therapeutics is developing both drugs and this study was conducted under contract with the Joint Product Management Office of BioDefense Therapeutics.

AVI-6602 is a combination of PMOs AVI-7537 and AVI-7639 while AVI-6603 is a combination of PMOs AVI-7287 and AVI-7288.  The 4 PMOs have a positive charge on them (“PMOplus”) that target specific mRNA sequences of viral proteins.  Animal studies have shown AVI-6002 to improve survival following Ebola exposure and AVI-6003 to improve survival following Marburg exposure. Heard et al tested the safety, tolerability, and pharmacokinetic properties of the two drugs in two identically designed randomized, double-blind, placebo-controlled studies in healthy volunteers.

Study Design and Results

In each of the two studies, 30 healthy male and female subjects between 18 and 50 years of age were enrolled in 6-dose escalation cohorts of 5 subjects each and received a single i.v. infusion of active study drug (0.005, 0.05, 0.5, 1.5, 3, and 4.5 mg/kg per component) or placebo in a 4:1 ratio.

The studies found that both AVI-6002 and AVI-6003 were safe and well tolerated at the doses studied and a maximum tolerated dose was not observed in either study. Pharmacokinetic properties were similar with the two drugs with estimated plasma half lives of 2 to 5 hours.

In a press release, Michael Wong, senior medical director, infectious diseases at Sarepta Therapeutics said:

“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.”

“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% of the non-human primates to Ebola and Marburg virus challenge infections, respectively.”

While AVI-6002 appears to be safe in humans and effective in animal models, it has yet to be tested in humans infected with Ebola.


Heald AE, Iversen PL, Jay B. Saoud JB, et al.  Safety and Pharmacokinetic Profiles of Phosphorodiamidate Morpholino Oligomers with Activity against Ebola Virus and Marburg Virus: Results of Two Single-Ascending-Dose Studies. Antimicrob. Agents Chemother. 2014;58:6639-47. doi:10.1128/AAC.03442-14

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