Humanized Monoclonal Antibodies Improve Survival in an Animal Model of CDAD

Progenics Pharmaceuticals, Inc. today presented pre-clinical findings for its humanized monoclonal antibodies against the disease-causing toxins produced by the bacterium Clostridium difficile (C. difficile). C. difficile is the leading cause of hospital-acquired diarrhea in the United States and represents a serious global public health challenge. In a well-established hamster model of C. difficile-associated disease (CDAD), treatment with Progenics' antitoxin antibodies resulted in 95 percent survival versus 0 percent survival for standard antibiotic treatment. The data are being presented at the 50th annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in Boston.

"Our novel antibodies represent a non-antibiotic treatment strategy that is designed to block the harmful effects of toxins A and B produced by C. difficile," said William C. Olson, PhD, senior vice president of research and development at Progenics. "Our humanized antitoxin monoclonal antibodies provided potent and durable protection against CDAD in the study reported today, and these results were achieved without co-use of antibiotics. This new approach has the potential to treat severe cases of CDAD and to break the cycle of infection in patients with relapsed disease."

In the preclinical efficacy study, two humanized monoclonal antibodies (one against toxin A and the other against toxin B) were tested in combination. Hamsters were infected with C. difficile in the presence or absence of treatment with antitoxin antibodies or vancomycin, a current standard antibiotic therapy. Nineteen of twenty (95 percent) animals treated with antibodies survived until the end of the 40-day study. In contrast, none of the eight vancomycin-treated animals survived more than 22 days, and none of the eight control (untreated) animals survived more than three days. The survival advantage provided by antibody treatment was highly statistically significant (P<0.0001) relative to both the vancomycin and control groups.

The poster, "Mechanistic Studies of Novel Monoclonal Antibodies against Clostridium difficile Toxins," was scheduled for presentation today, Sept. 13, 2010 by Andre J. Marozsan, PhD, associate director of biologics discovery at Progenics Pharmaceuticals, Inc.