From rxpgnews.com
A Non-Antibiotic Approach to Deal with Clostridium difficile associated diarrhea
By Genzyme Corporation
Apr 4, 2005, 21:43
Genzyme Corporation (Nasdaq: GENZ) announced today that physicians have treated the first patients in a Phase 3 clinical study to test the safety and efficacy of tolevamer, an investigational polymer therapy for patients with Clostridium difficile associated diarrhea (CDAD), a form of infectious diarrhea caused by the bacterium C. difficile.
Tolevamer is being developed as a new, non-absorbed therapy that could be the first non-antibiotic treatment approved for CDAD. Tolevamer is designed to bind and remove from the body toxins released by C. difficile that damage the intestine.
A non-antibiotic approach has the potential to treat CDAD and reduce the number of disease recurrences, resulting in improved quality of life for the patient and significant savings to the healthcare system.
C. difficile is a spore-forming bacterium that is found widely in the environment and is known to survive for months in hospitals and long-term care facilities. 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 and the
number of reported cases of CDAD infections has increased in recent years.
"C. difficile represents a significant risk to many hospital and long-term care patients, especially among the elderly," said Georges Gemayel, executive vice president of Genzyme Corp."Tolevamer is being developed as a much-
needed alternative to antibiotics to treat this devastating and sometimes fatal infection that now affects thousands of people each year. We are encouraged by data that indicate that tolevamer may be particularly valuable in reducing recurrence and repeat hospitalization for these patients."
The Phase 3 study will be conducted at more than 250 clinical sites in North America, Europe and Australia, and involve more than 1,000 patients. Enrollment is expected to take approximately eighteen months to complete.
The randomized, double-blinded study will include three arms and have a primary endpoint of non-inferiority to the standard prescribed oral dose of the antibiotic vancomycin, measured by the percent of patients with resolution
of CDAD. Half of the patients enrolled in the study will receive tolevamer in a new liquid formulation designed for ease of use.
The study also will evaluate tolevamer against metronidazole, the most commonly prescribed antibiotic treatment for CDAD. In addition, 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. The study is also designed to measure the
superiority of tolevamer based on the number of CDAD recurrences against both vancomycin and metronidazole.
Tolevamer has been evaluated in five clinical studies to date, including a large Phase 2 efficacy study, two open-label clinical trials in CDAD patients, a Phase 1 trial in healthy volunteers and an additional Phase 1 tolerability
study evaluating the new liquid formulation. Data from this last study show the new liquid formulation of tolevamer to be well-tolerated at all dosing levels tested up to a maximum of 15 grams. The daily dose of tolevamer in the Phase 3 study is 9 grams. The results from the Phase 1 study are being presented this week at the European Congress of Clinical Microbiology and Infectious Diseases in Copenhagen.
Genzyme has become a worldwide leader in developing polymer-based therapies for serious diseases, including Renagel(R) (sevelamer hydrochloride) and WelChol(R) (colesevelam hydrochloride). In each case, the polymers are designed to provide clinical benefit by binding and removing unwanted
substances from the body.
Clostridium difficile is the most common cause of infectious, hospital-based diarrhea and, although incidence is not officially tracked, may result in more than 400,000 cases of diarrhea and colitis annually in the United States, leading to death in about 5,000 cases.
C. difficile proliferates in the setting of altered normal colonic bacterial flora, most commonly due to the administration of broad-spectrum antibiotics. Once established in the colon, C. difficile produces toxins that
disrupt the intestinal lining, causing cell death and inflammation that result in diarrhea and colitis.
Vancomycin is currently the only therapy approved by the U.S. Food and Drug Administration for 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.
All rights reserved by www.rxpgnews.com