MGAWN1 (West Nile Virus)

MacroGenics is developing MGAWN1, a humanized monoclonal antibody, for the treatment of individuals with suspected central nervous system infection due to West Nile Virus (WNV). In July 2009, MacroGenics announced the initiation of the PARADIGM trial, a Phase 2 clinical study evaluating MGAWN1. 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 the drug to be safe and well tolerated at all doses tested. 

Currently, there are no approved treatments for individuals with severe West Nile Virus infection. These 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. 

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.  MGAWN1 has a specific activity that is orders of magnitude higher than that of an intravenous immune globulin (IVIG) product when tested in laboratory studies.

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. Approximately 20 sites in North America will be utilized for the conduct of 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 has widespread prevalence throughout the United States and other parts of North America. Approximately 20% of humans infected with WNV experience West Nile Fever with clinical symptoms that include fever, headache, body aches, skin rash and swollen lymph glands. In approximately 1% of human infections, WNV enters the brain and causes severe, life-threatening neuroinvasive disease in the form of encephalitis, meningitis or acute flaccid paralysis. West Nile Neuroinvasive Disease (WNND) is associated with significant morbidity, and long-term neurological effects are common among survivors. 

Since 1999, there have been more than 28,000 cases of confirmed symptomatic WNV infection in the United States, which include more than 11,000 WNND cases and more than 1,100 deaths. In 2008, 1,356 cases of WNV infection were reported to the Centers for Disease Control and Prevention (CDC) for the year with 44 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 2008 West Nile Virus Activity in the United States

The map below reflects surveillance findings occurring between January 1, 2008 through December 31, 2008 as reported to CDC's ArboNET system for public distribution by state and local health departments (source: CDC&rsquos West Nile Virus website).

Learn More:

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