Infectious diseaseTwo RNA-based therapeutic candidates for Ebola, Marburg viruses

Published 23 March 2012

Under a contract for up to $291 million from the U.S. Department of Defense, AVI BioPharma has initiated clinical studies for two RNA-based drugs for the treatment of Ebola and Marburg viruses


Bothell, Washington-based AVI BioPharma, Inc., a developer of RNA-based therapeutics, the other day announced that it initiated dosing in two Phase 1 clinical studies for AVI-6002 and AVI-6003, its lead drug candidates being evaluated for the treatment of Ebola virus and Marburg virus, respectively. AVI is developing AVI-6002 and AVI-6003 under a competitively awarded contract for up to $291 million from the U.S. Department of Defense through the Joint Project Manager Transformational Medical Technologies (JPM-TMT) program. Both candidates utilize AVI’s advanced and proprietary PMOplus(tm) chemistry.

These are the first drug candidates employing our PMOplus chemistry to be evaluated in humans, and they are the first AVI programs to enter the clinic based on our prior studies supported by the JPM-TMT program,” said Chris Garabedian, president and CEO of AVI BioPharma. “Additionally, we look forward to new and continued opportunities to earn further government support through JPM-TMT.”

Each Phase 1 study will be randomized, double-blind, placebo-controlled and involve single escalating doses of AVI-6002 or AVI-6003 to assess the safety, tolerability and pharmacokinetics of each drug candidate in healthy adult volunteers. In each study, five volunteers will be enrolled in one of six cohorts for a total of up to 30 volunteers. The cohorts will include four volunteers who receive the therapeutic, and one who will receive a placebo.

Preclinical studies of AVI-6002 and AVI-6003 have been a collaborative effort between AVI and scientists at the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), the U.S. Department of Defense’s (DOD) lead medical research laboratory for biological defense. All preclinical studies were conducted at USAMRIID, which has the DOD’s only Biosafety Level 4 (BSL4), or maximum containment capability, and is essential for studying the Ebola and Marburg viruses.

The company notes that data from preclinical studies published in Nature Medicine demonstrate that AVI-6002 and AVI-6003 provide post-exposure efficacy in non-human primates against Ebola and Marburg viruses, respectively. In multiple studies evaluating treatment of Ebola virus-infected primates with AVI-6002 and treatment of Marburg-infected primates with AVI-6003, USAMRIID scientists have observed up to 80 percent survival and 100 percent survival, respectively, when the viruses were inoculated at 1000 times the lethal dose within the confines of a BSL4 laboratory, compared to control groups where both viruses were universally lethal.

Ebola hemorrhagic fever is a severe and often fatal disease in humans. The disease was first recognized in 1976 and is one of two members of a family of RNA viruses called Filoviridae. The disease is generally understood to be endemic to parts of Africa. Onset of illness from Ebola virus is abrupt with symptoms that include fever, headache, muscle ache, vomiting and stomach pain. Internal and external bleeding may also be observed in some patients. There are currently no treatments for Ebola virus infection beyond supportive care.

Marburg hemorrhagic fever is another severe and potentially fatal disease in humans first recognized in 1967. It is also caused by an RNA virus of the filovirus family and is understood to be endemic to Africa. Onset of the disease is often sudden, and the symptoms include fever, chills, nausea, vomiting, chest pain and diarrhea. Increasingly severe symptoms may also include massive hemorrhaging and multiple organ dysfunctions. There are currently no treatments for Marburg virus infection beyond supportive care.