Study shows effectiveness of Peramivir in mouse model of H5N1 virus infection

May 4 2007

BioCryst Pharmaceuticals has announced that investigators at St. Jude Children's Research Hospital, Memphis, TN, reported favorable results evaluating peramivir treatment in an animal model of influenza using a highly virulent strain of H5N1 virus (an avian influenza strain that had caused fatal human infection in Viet Nam).

The study, presented on April 30, 2007 by Dr. David Boltz at the 20th International Conference on Antiviral Research, Palm Springs, CA, concluded that peramivir is an effective treatment when administered intramuscularly to control H5N1 infection in mice and that these data support the potential use of this drug to control influenza in the event of a pandemic.

The objective of the study was to achieve complete protection against lethal H5N1 influenza virus infection in the mouse model through the use of intramuscular administration of peramivir, a potent neuraminidase inhibitor with antiviral activity against strains of influenza viruses, including seasonal strains and influenza H5N1 strains from avian origins.

A survival rate of 40% to 60% was observed in mice treated with one or two injections of peramivir; however, 100% survival of mice was achieved by two injections of peramivir on the first day followed by once-daily administration for 7 days. The longer duration of peramivir treatment also prevented viral replication in the tissues of the lungs, brain and spleen of the mice at the 3, 6, and 9 day post-inoculation time points.

W. James Alexander, MD, MPH, BioCryst Senior Vice President for Clinical Operations commented, "The results of this St. Jude study, performed under the careful guidance of Drs. Elena Govorkova and Robert Webster, bolsters our confidence that peramivir may be clearly beneficial in the treatment of severe influenza, including human influenza due to strains of avian origin. We wish to congratulate our colleagues at St. Jude on the successful conduct of an elegant study which not only confirms but significantly extends the observations of the previous animal study reported last year by NIH showing positive effects of peramivir in a similar model of H5N1 influenza virus infection."

BioCryst is advancing the clinical development of peramivir under terms of a contract from the U.S. Department of Health and Human Services (DHHS) which on January 4, 2007 awarded BioCryst a $102.6 million, four-year contract to develop peramivir for the treatment of seasonal and life-threatening influenza. Funding from the contract will support manufacturing of clinical lots, process validation, clinical studies and other product approval requirements needed for U.S. licensure. BioCryst retains 100% development and commercialization rights to peramivir worldwide other than in Japan and Korea where BioCryst recently established strategic partnerships with Shionogi & CO. in Japan, and Green Cross in Korea.

Peramivir is a member of the class of antiviral agents that inhibit influenza viral neuraminidase, an enzyme that is essential for the spread of influenza virus within the host. Peramivir is an inhibitor of influenza A and B neuraminidases and certain strains of influenza viruses that may be resistant to available neuraminidase inhibitors are susceptible to peramivir in laboratory tests. At the 46th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy in September, 2006, data were presented showing that injectable formulations of peramivir were safely administered to healthy subjects at daily doses up to approximately 600 mg. At the same meeting, animal data were presented showing peramivir promoted survival in animals infected with highly pathogenic strains of the H5N1 virus. Peramivir injection has received Fast Track designation from US FDA and the availability of an intravenous neuraminidase inhibitor may be important in treating patients hospitalized with severe and potentially life-threatening influenza. The availability of an intramuscular formulation of peramivir could ensure appropriate dosing which may be a concern with currently available oral or inhaled anti-influenza agents.

The influenza virus causes an acute viral disease of the respiratory tract. Unlike the common cold and some other respiratory infections, seasonal flu can cause severe illness, resulting in life-threatening complications. According to the Centers for Disease Control and Prevention, every year in the United States more than 200,000 people are hospitalized from flu complications, and about 36,000 people die from flu. Most at risk are young children, the elderly, and people with seriously compromised immune systems.

Avian influenza A viruses of H5N1 subtype are circulating among birds worldwide, the virus is considered extremely contagious in fowl. It is believed that all species of birds are susceptible to avian influenza, but domestic poultry, including chickens and turkeys, are among the more susceptible to the highly pathogenic strain. According to the World Health Organization, at least 261 people have contracted H5N1 avian influenza, of which at least 157 have died. Almost all of these infections are believed to have resulted from contact with infected poultry.