Influenza
AVI is applying our leading RNA-based technology platform to the research and development of therapeutic drug candidates against influenza viruses. AVI-7100 is our lead influenza therapeutic drug candidate and was developed using our patented PMOplus™ technology that attaches positionally specific positive charges to its PMO, or phosphorodiamidate morpholino oligomer, backbone to improve selective interaction between the drug and its target. This is the same chemistry used to generate our investigational drug candidates against hemorrhagic fever viruses. We believe AVI-7100 has significant potential as a broad-spectrum influenza therapeutic since its target appears well conserved across various influenza strains, including seasonal flu strains.
The influenza program is supported by contracts with the U.S. Defense Threat Reduction Agency (DTRA) and conducted in cooperation with the U.S. Department of Defense’s Transformational Medical Technologies program (TMT). We have received funding commitments from the U.S. government totaling up to $26 million to advance the development of AVI-7100 into Phase 1 and to evaluate its therapeutic potential against the H5N1 (avian flu), H3N2 (seasonal flu) and Tamiflu™ resistant flu strains.
Please see our Biodefense Programs for more information.
Development Status
In 2009 TMT contracted a rapid response exercise with us against a real-world emerging threat, the pandemic H1N1 virus, or swine flu. The intent of the exercise was to demonstrate our capability to efficiently respond to a real-world emerging viral threat by rapidly designing and producing multiple therapeutic candidates and evaluating their preclinical efficacy.
Initially the exercise involved identifying target sequences against H1N1, designing several drug candidates utilizing proprietary derivatives of our PMO chemistry and then manufacturing the candidates in sufficient quantity for preclinical testing. This was successfully accomplished in approximately one week, demonstrating our ability to rapidly respond to a real-world viral threat utilizing our RNA-based therapeutics platform.
Subsequently, we evaluated our RNA-based drug candidates in preclinical studies using a mouse model of seasonal flu and identified AVI-7100, our lead influenza therapeutic drug candidate that employs our patented PMOplus™ technology. We then conducted two preclinical in vivo studies of AVI-7100 utilizing a fully virulent human pandemic H1N1 virus in a ferret model.
The ferret studies included various treatment groups employing different doses of AVI’s lead drug candidate, a scrambled sequence control, a saline control and a positive control utilizing a standard of care drug, Tamiflu®. In the first ferret study, AVI-7100 showed a statistically significantly greater reduction in viral titer than was seen with the scrambled sequence control, the saline control or the positive control using Tamiflu®.
Clinical symptom scores in ferrets from the first study also exhibited statistically significant improvements versus controls. Improvements were demonstrated in scores measuring respiratory distress, sneezing, nasal discharge, fever, activity level and weight loss/gain, versus saline control and positive scramble and Tamiflu® controls.
Results from the second ferret study have not yet been announced.
In April 2010 (Read Press Release) we received increased funding from DTRA to support continued preclinical development of AVI-7100 against H1N1 as well as its expanded preclinical evaluation against H5N1 (avian flu) and drug resistant H1N1 and H3N2 flu strains. In June 2010, (Read Press Release) we entered into a new contract with DTRA to advance the development of AVI-7100, including studies enabling an Investigational New Drug (IND) application with the U.S. Food and Drug Administration, the study of an intranasal delivery formulation and the funding of a Phase 1 clinical trial to obtain human safety data to support potential use under an Emergency Use Authorization.
About Pandemic H1N1 Influenza
On June 11, 2009 the World Health Organization declared a pandemic of H1N1 influenza. The virus was first detected in people in the U.S. in April 2009 and was referred to as “swine flu” because many of the genes in the virus were very similar to those found in flu viruses that circulate in pigs (swine). Illness with the 2009 H1N1 virus has ranged from mild to severe. Symptoms include fever, cough, runny nose, headache, chills and fatigue. Many people infected with H1N1 also have respiratory symptoms without a fever. Severe illness and deaths have occurred as a result of illness associated with the virus.
The Centers for Disease Control and Prevention (CDC) estimated that between April 2009 and January 16, 2010 there were up to 84 million cases of H1N1 infection in the U.S. The CDC also estimated that there were up to 378,000 H1N1-related hospitalizations in the U.S. during the same time period.
The information set forth above is current only as of the dates noted. While we will make reasonable attempts to keep the information current, there is no guarantee that we will be successful and, except as required under applicable federal and state laws, we disclaim any obligation to do so. Readers are invited to visit the press release and SEC documents sections of this website for more up to date information about the Company and its research, development and clinical programs as well as other aspects of its business.
This page was last updated on July 22, 2010.
