Actoxumab/Bezlotoxumab

PRINCETON, N.J., and JAMAICA PLAIN, Mass., Sept. 6 /PRNewswire-FirstCall/ -- Medarex, Inc. (Nasdaq: MEDX - News) and The Massachusetts Biologic Laboratories (MBL) of the University of Massachusetts Medical School (UMMS) today announced the commencement of a randomized, double-blind, placebo-controlled Phase II clinical trial of CDA-1 (also referred to as MDX-066) and MDX-1388, two novel fully human monoclonal antibodies developed to Clostridium difficile (C. difficile) Toxin A and Toxin B, respectively, for the treatment of C. difficile associated diarrhea (CDAD). The single-dose Phase II clinical trial is expected to enroll up to 200 patients with CDAD and is designed to assess the efficacy of the combination of CDA-1 and MDX-1388 against placebo as an addition to standard of care antibiotics to resolve CDAD more quickly and to prevent subsequent relapse of disease. "CDAD is a growing and potentially serious epidemic, particularly in the twenty to fifty percent of hospitalized patients who relapse after receiving antibiotic treatment," said Donna Ambrosino, MD, Director of the MBL and a professor of pediatrics at UMMS. "We believe that the development of antibodies against the toxins could address this significant and costly public health problem." A newly identified epidemic strain of C. difficile has been implicated in severe outbreaks of CDAD in the United States, Canada and the United Kingdom, and has affected otherwise healthy individuals in the community. The virulence of the new strain has been attributed, at least in part, to a markedly increased efficiency of production of Toxins A and B. The epidemic strain appears to cause more severe illness initially and to subsequently result in a higher rate of relapse. As previously announced, data presented at the 2005 Infectious Disease Society of America (IDSA) showed that the CDA-1 and MDX- 1388 antibodies effectively neutralized the toxins from the newly identified epidemic strain of C. difficile in a preclinical study. Dr. Ambrosino noted, "We have conducted studies in a stringent animal model of acute CDAD that showed that the combination of both CDA-1 and MDX- 1388 increased survival when compared to either antibody alone, with an efficacy comparable to antibiotic treatment. Additionally, in an animal model to study the relapse of CDAD after withdrawal of antibiotics, the combination of the antibodies was highly effective in preventing relapse, and clearly superior to each antibody alone." MBL and Medarex have now completed Phase I studies in healthy volunteers with CDA-1 and MDX-1388 alone and in combination, which demonstrated good tolerability and expected pharmacokinetic parameters. An ongoing Phase II study to examine the efficacy of CDA-1 alone against placebo in combination with standard of care in patients with CDAD has now been stopped early in favor of collecting clinical efficacy data on what is expected to be the more potent combination of CDA-1 and MDX-1388. "We have seen very encouraging preclinical data indicating that the combination of the two antibodies is potentially more effective than either antibody alone in treating and preventing recurrence of CDAD," said Dr. Israel Lowy, Medarex's Senior Director of Clinical Science and Infectious Disease. "Now that we have Phase I data indicating the safety of MDX-1388 and its combination with CDA-1, we are taking the earliest opportunity to start a Phase II trial with the combination which was so clearly most effective in pre-clinical efficacy studies in CDAD." About CDA-1 (MDX-066) and MDX-1388 CDA-1 (MDX-066) and MDX-1388 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 Clostridium difficile (C. difficile) and which are associated with a serious and sometimes deadly form of diarrhea called C. difficile associated diarrhea (CDAD). Published epidemiologic studies of hospitalized patients at risk for CDAD have shown a positive correlation between detectable levels of antibody in the blood to toxin A and protection from disease or relapse. Public health officials estimate that there are approximately 300,000 cases of CDAD among hospitalized patients each year in the United States with approximately two percent deaths. CDAD is typically treated with antibiotics; however, prolonged illness can occur, and between 20-25 percent of those affected by CDAD suffer a relapse of the disease. About MBL The Massachusetts Biologic Laboratories is the only non-profit FDA- licensed manufacturer of vaccines and other biologic products in the United States. 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 UMass Medical School since 1997. About UMass Medical School The University of Massachusetts Medical School 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 $174 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 for additional information. About Medarex 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® 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. Thirty-three of these therapeutic product candidates derived from Medarex technology are in human clinical testing or have had INDs submitted for such trials, with five of the most advanced product candidates currently in Phase III clinical trials. 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 Medarex Statement on Cautionary Factors Except for the historical information presented herein, matters discussed herein may constitute forward-looking statements 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 "potential"; "believe"; "anticipate"; "intend"; "plan"; "expect"; "estimate"; "could"; "may"; or similar statements are forward-looking statements. Medarex disclaims, however, any intent or obligation to update these forward-looking statements. Risks and uncertainties include risks associated with product discovery and development, uncertainties related to the outcome of clinical trials, slower than expected rates of patient recruitment, unforeseen safety issues resulting from the administration of antibody products in patients, uncertainties related to product manufacturing 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, 2005 and subsequent Quarterly Reports on Form 10-Q. There can be no assurance that such development efforts will succeed or that other 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. 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