MGAWN1 and West Nile Virus

MacroGenics is developing the drug, MGAWN1, a humanized monoclonal antibody, for the treatment of individuals with West Nile Fever shown by laboratory tests or suspected central nervous system infection due to West Nile Virus (WNV).  In July 2009, MacroGenics announced the start of the PARADIGM trial, a Phase 2 clinical study evaluating MGAWN1 resumed for the 2010 season in May.  Before this Phase 2 trial began, MacroGenics completed a Phase 1 study of MGAWN1 in healthy volunteers.  This randomized, double-blind, dose-escalation cohort study was designed to evaluate the safety, tolerability, and pharmacokinetics of a single infusion of MGAWN1 in healthy adults. The study demonstrated adequate safety and was tolerated well at all doses tested. 

Currently, there are no approved treatments for people with severe West Nile Virus infection.  Such patients are hospitalized and receive supportive care.  Therefore, a therapy that neutralizes the virus and could possibly reduce or prevent complications associated with West Nile Neuroinvasive Disease would represent a significant advancement for these patients.  Also, recent data show long-term complications of fever associated with West Nile infection.  For this reason, we are also expanding the trial to include patients with West Nile Fever.

MacroGenics’ MGAWN1 program is funded through a $50 million contract with the National Institutes of Health, National Institute of Allergy and Infectious Diseases (NIAID). 

About MGAWN1 

MGAWN1 is a humanized monoclonal antibody (IgG1 kappa) that specifically recognizes the envelope (E) protein of WNV.  MGAWN1 exhibits potent neutralizing and fusion-inhibitory activity against WNV in laboratory studies conducted in vitro and in vivo.  in laboratory studies, MGAWN1 has a specific activity that is much higher than that of an intravenous immune globulin (IVIG) product.

Paradigm Clinical Trial
 
The Paradigm trial is a randomized, double-blind, multicenter, placebo-controlled Phase 2 clinical study that is designed to evaluate the safety and efficacy of MGAWN1 in patients > 18 years of age with signs and symptoms of acute West Nile Neuroinvasive Disease as well as West Nile Virus Fever patients with laboratory evidence of infection with the virus.  Approximately 25 clinical sites in North America will take part in the Paradigm trial.  A map of the anticipated study sites is provided below (green pushpins represent active sites, yellow pushpins represent further anticipated sites).

Disease Background: West Nile Virus 

West Nile virus cases have occurred throughout the United States and other parts of North America. About 20% of humans infected with WNV experience West Nile Fever with symptoms that include fever, headache, body aches, skin rash and swollen lymph glands. In about 1% of human infections, WNV enters the brain and spinal cord causes severe, life-threatening neuroinvasive disease in the form of encephalitis (inflammation of the brain), meningitis (inflammation of the coverings of the brain and spinal cord) or acute flaccid paralysis. West Nile Neuroinvasive Disease (WNND) is associated with significant illness, and long-term effects on the nervous system are common among survivors . 

Since 1999, there have been more than 29,000 cases of confirmed symptomatic WNV infection in the United States, which include more than 12,000 WNND cases and more than 1,100 deaths. In 2009, 722 cases of WNV infection were reported to the Centers for Disease Control and Prevention (CDC) for the year with 33 of these cases resulting in death. WNV is now the most common cause of epidemic viral encephalitis in the U.S., and it will likely remain an important cause of neurological disease for the foreseeable future. Since 2002, more than 4,500 cases of clinical WNV infection have been reported in Canada. No effective therapy or vaccine is available for humans .

Final 2009 West Nile Virus Activity in the United States

The map below reflects surveillance findings occurring between January 1, 2009 through December 31, 2009 as reported to CDC's ArboNET system for public distribution by state and local health departments (source: CDC & West Nile Virus website).

Learn More:

• Paradigm Study (www.clinicaltrials.gov)
• Contact us regarding the Paradigm Study 
• Relevant Publications