Medarex and Massachusetts Biologic Laboratories Announce Primary Objective Achieved in Phase 2 Trial of Monoclonal Antibody Combination for the Treatment of Clostridium difficile Associated Diarrhea (CDAD)
Top-line data from randomized, double-blind, placebo controlled Phase 2 clinical trial indicate statistically significant reduction in recurrences of CDAD
PRINCETON, N.J. and JAMAICA PLAIN, Mass., November 03, 2008 /PRNewswire-FirstCall/ -- Medarex, Inc. and The Massachusetts Biologic Laboratories (MBL) of the (UMMS) today announced that a Phase 2 trial of an anti-C. difficile antibody combination treatment in patients with C. difficile Associated Diarrhea (CDAD) successfully met its primary objective. The top-line results from the recently completed multi- center, randomized, double-blind, placebo-controlled Phase 2 trial indicated a statistically significant reduction in recurrences of CDAD when compared with placebo. In the study, 200 patients symptomatic with CDAD receiving standard of care antibiotics (metronidazole or vancomycin) were randomized to receive either intravenous placebo or intravenous administration of a combination of MDX-066 (CDA-1) and MDX-1388 (CDB-1), two fully human antibodies that neutralize C. difficile toxins A and B, respectively.
Consistent with the published literature, the recurrence rate in the placebo-treated group exceeded 20 percent for patients following successful treatment with standard of care antibiotics. In comparison with placebo, MDX- 066/MDX-1388 treatment reduced recurrence rates by approximately 70 percent (p=0.0004 on the intent-to-treat population). The antibody combination treatment was generally safe and well-tolerated. Full results from this Phase 2 trial are planned to be presented at a future scientific meeting.
The incidence and mortality associated with CDAD has been increasing(1), with estimates of over 500,000 cases in the United States, and approximately 15,000 deaths caused or contributed by C. difficile.(2) The emergence of a highly virulent epidemic strain that produces much higher levels of toxins A and B has also been associated with morbidity and mortality in younger, healthier, and non-hospitalized patients.(3)
"We are delighted with these dramatic results. CDAD is a growing and serious epidemic, with twenty to fifty percent of hospitalized patients relapsing after receiving antibiotic treatment," said Donna Ambrosino, MD, Executive Director of the MBL and Professor of Pediatrics at UMMS. "The demonstration of significant protection from relapse indicates that treatment with monoclonal antibodies against the toxins could reduce this significant and costly public health problem."
"These results highlight the exquisite specificity of monoclonal antibodies and their important role to save lives," said Howard H. Pien, President and CEO of Medarex. "We believe that the strength of our antibody technology platform for generating potentially important treatment options, such as the C. difficile program antibodies, will continue to shape the future of medicine. Furthermore, Medarex's strategy of proving the utility of potentially promising candidates for development by well-designed and well- executed studies is amply demonstrated."
About Clostridium difficile Acquired Diarrhea (CDAD)
C. difficile is a spore forming bacterium that is common in the environment and can colonize the gastrointestinal (GI) tract. It can be easily spread among hospitalized patients and residents of long term care facilities, but also can be found in otherwise healthy individuals in the community. The origin of disease is believed to develop in the presence of antibiotics administered for other infections, in which the complex microbial make up of the GI tract is altered, and C. difficile spores may germinate, grow, and produce toxins A and B. The toxins cause damage to the GI tract lining in the colon, resulting in severe diarrhea, and may lead to perforations of the colon and/or death. Treatment of severe disease requires administration of additional antibiotics to kill the C. difficile bacteria, but because of the persistence of spores, as well as the difficulty for the intestinal flora to re-normalize in the setting of antibiotics, relapse/recurrence of CDAD is common, and is estimated to occur in 20 percent of cases, with post-therapy recurrence rates as high as 60 percent.(4) Recurrence can be difficult to manage and is a challenging complication of CDAD; however, the use of non- antibiotic based approaches to neutralization of C. difficile toxins may be important options needed to facilitate recovery of the GI flora.(5)
More information on CDAD can be accessed through the following websites:
Centers for Disease Control and Prevention website at www.cdc.gov/ncidod/dhqp/id_Cdiff.html
ICAAC/IDSA 2008 website for abstracts at www.icaacidsa2008.org/
About MDX-066 (CDA-1) and MDX-1388 (CDB-1)
MDX-066 (CDA-1) and MDX-1388 (CDB-1) are novel, fully human antibodies that were developed by MBL and Medarex to target and neutralize the effects of toxin A and toxin B, respectively, the toxins produced by the bacterium C. difficile and which are associated with a serious and sometimes deadly form of diarrhea called C. difficile associated diarrhea. Published epidemiologic studies of hospitalized patients at risk for CDAD have shown a positive correlation between detectable levels of antibody in the blood to both toxins A and B and protection from disease or relapse.
In a presentation at the recent joint meeting of the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) and the Infectious Diseases Society of America (IDSA) in Washington, DC, MBL and Medarex presented clinical data that demonstrated the requirement for anti-C. difficile toxin B antibody in addition to anti-C. difficile toxin A antibody for protection in patients with CDAD. These results suggest that the use of antibodies to both toxins may optimally protect against occurrence and are consistent with animal studies conducted by the two companies.
The Massachusetts Biologic Laboratories is the only non-profit FDA- licensed manufacturer of vaccines and other biologic products in the United States. MBL produces 30 percent of the U.S. Td vaccine supply. In addition to the C. difficile program, MBL has discovered and developed human monoclonal antibodies for rabies and Hepatitis C, which are expected to enter clinical trials in 2009. The laboratory was established in 1894 and since then the MBL's mission has been to improve public health through applied research, development and production of biologic products. MBL has been a part of the since 1997.
The is one of the fastest growing academic health centers in the country and has built a reputation as a world-class research institution, consistently producing noteworthy advances in clinical and basic research. The Medical School attracts more than $193 million in extramural research funding annually. Research dollars enable UMMS scientists to explore human disease from the molecular level to large-scale clinical trials. Basic and clinical research has led to new approaches for diagnosis, treatment and prevention of disease. Visit www.umassmed.edu for additional information.
Medarex is a biopharmaceutical company focused on the discovery, development and potential commercialization of fully human antibody-based therapeutics to treat life-threatening and debilitating diseases, including cancer, inflammation, autoimmune disorders and infectious diseases. Medarex applies its UltiMAb(R) technology and product development and clinical manufacturing experience to generate, support and potentially commercialize a broad range of fully human antibody product candidates for itself and its partners. Over forty of these therapeutic product candidates derived from Medarex technology are in human clinical testing or have had INDs submitted for such trials, with the most advanced product candidates currently in Phase 3 clinical trials or the subject of regulatory applications for marketing authorization. Medarex is committed to building value by developing a diverse pipeline of antibody products to address the world's unmet healthcare needs. For more information about Medarex, visit its website at www.medarex.com.
Medarex Statement on Cautionary Factors
Except for the historical information presented herein, the statements in this press release may constitute forward-looking statements, as defined in the Private Securities Litigation Reform Act of 1995, that are subject to certain risks and uncertainties that could cause actual results to differ materially from any future results, performance or achievements expressed or implied by such statements. Statements that are not historical facts, including statements preceded by, followed by, or that include the words "may"; "potential"; "preliminary"; "could"; "believe"; or similar statements are forward-looking statements. Medarex disclaims any intent or obligation to update these forward-looking statements. Risks and uncertainties include risks associated with the development of MDX-066 and MDX-1388, unforeseen safety issues resulting from the administration of antibody products in patients, as well as risks detailed from time to time in Medarex's public disclosure filings with the U.S. Securities and Exchange Commission (SEC), including its Annual Report on Form 10-K for the fiscal year ended December 31, 2007 and its quarterly reports on Form 10-Q. There can be no assurance that such development efforts will succeed or that developed products will receive required regulatory clearance or that, even if such regulatory clearance were received, such products would ultimately achieve commercial success. Copies of Medarex's public disclosure filings are available from its investor relations department.
Medarex(R), the Medarex logo, UltiMAb(R) and HuMAb(TM) are trademarks of Medarex, Inc. All rights are reserved.
(1) Redelings MD et al. "Increase in Clostridium difficile-related mortality rates, United States, 1999-2004." Emerging Infectious Diseases. 2007; 13(9):1417-1419.
(2) "Current Trends: Is the Epidemic Ongoing?" presentation (#3635) by LC McDonald at 2008 ICAAC/IDSA.
(3) McDonald, LC et al. "An epidemic, toxin gene-variant strain of Clostridium difficile." The New England Journal of Medicine. 2005; 353(23):2433-2441.
(4) Kelly CP et al. "Clostridium difficile: more difficult than ever." The New England Journal of Medicine. 2008; 3359(18):1932-1940.
(5) Sunenshine RH et al. "Clostridium difficile-associated disease: new challenges form an established pathogen." Cleveland Clinic Journal of Medicine. 2006; 73(2):187-197.
CONTACT: Laura S. Choi, Investor Relations, +1-609-430-2880, ext. 2216, orNichol Ochsner, Corporate Communications, +1-609-430-2880, ext. 2214, bothof Medarex, Inc.; or Michael Cohen, +1-508-856-2000, or +1-508-868-4778(cell), , for UMMS/MBL Michael.Cohen@umassmed.edu
Web site: http://www.medarex.com/
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Posted: November 2008