CAMBRIDGE, Mass. -- Genzyme Corporation announced that results from its phase 2 trial of tolevamer, an investigational polymer therapy for patients with Clostridium difficile-associated diarrhea (CDAD), have been published in the August 15 issue of Clinical Infectious Diseases.
Tolevamer is a novel therapy that could be the first non-antibiotic treatment approved for CDAD, a sometimes deadly form of infectious diarrhea caused by the bacterium C. difficile. Tolevamer is designed to bind and remove from the body toxins released by C. difficile that damage the large intestine. In an era of increasing concern about the overuse of antibiotics and the emergence of antibiotic resistance and "superbugs," tolevamer has the potential not only to treat CDAD, but also to reduce its rate of recurrence through a non-antibiotic mechanism of action that does not harm the normal intestinal bacteria that provide protection against C. difficile.
The phase 2 trial enrolled nearly 300 patients at 58 sites throughout the United States, Canada and the United Kingdom in a randomized, double-blind, active-controlled study to determine the safety and efficacy of tolevamer versus the standard prescribed dose of the antibiotic vancomycin. Vancomycin is the only therapy approved in the United States and Europe for treatment of CDAD. In the phase 2 study, tolevamer demonstrated similar treatment outcomes as vancomycin in terms of time to resolution of diarrhea, and a strong trend toward a reduced recurrence rate of CDAD.
C. difficile is estimated to affect approximately one percent of all hospitalized patients, and to result in more than 400,000 cases of diarrhea and colitis, and more than 5,000 deaths annually in the United States.
Patients are at risk of developing CDAD when they are treated with antibiotics that alter the normal, protective bacteria that reside in the colon. Virtually all antibiotics have been implicated in causing CDAD. Several deadly outbreaks of CDAD have occurred in the United States, Canada and Europe in recent years, and a new, more virulent strain of C. difficile recently was identified and tied to these outbreaks.
Phase 3 Studies Ongoing
Tolevamer is currently being studied in two concurrent clinical trials, the largest of their kind ever to be conducted for CDAD. One trial is taking place in North America, and the other in Europe and Australia. These studies, which began in April 2005, will involve more than 1,000 patients at approximately 300 sites.
In these trials, tolevamer is being compared to two antibiotic therapies, vancomycin and metronidazole, which are the most commonly prescribed treatments for CDAD. Because tolevamer is a non-antibiotic and will not harm the normal protective intestinal bacteria that prevent C. difficile proliferation, it is expected to reduce the rate of recurrent CDAD. Aside from testing tolevamer's efficacy, these are also the first large, rigorously designed, multi-center clinical studies comparing the efficacy of the current standards of care.
Genzyme expects to complete the tolevamer trials in 2007 and, pending regulatory review, the first commercial approval is anticipated in 2008. Tolevamer has been given fast-track designation by the U.S. Food and Drug Administration for the treatment of CDAD.
Even after successful treatment with the current standard of care, approximately 20 percent of patients experience a recurrence of CDAD which may require repeat hospitalization. In addition, a subset of patients with CDAD develop multiple recurrences of the disease, with symptoms that may persist for years.
Source: Genzyme Corporation