A Phase III study is under way to test tolevamer, Genzyme Corp.'s non-antibiotic therapy for patients with Clostridium difficile-associated diarrhea (CDAD).
"This particular disease is actually caused by antibiotics, and it's currently being treated by antibiotics," said Tim Olson, a project manager at Genzyme in charge of the tolevamer program. "It's part of the family of antibiotic-associated diarrhea, and it's the most common disease within that area."
The investigational polymer is a non-absorbed therapy, and should it eventually enter the market, it would represent the first non-antibiotic treatment approved for CDAD. It would not only serve as a treatment for the infection but also reduce the number of recurrences, resulting in improved quality of life and savings to the health care system, Genzyme said.
Patients are at risk of developing CDAD when they are treated with antibiotics that alter the protective bacteria that normally reside in the colon. Olson said about 20 percent of antibiotic-associated diarrhea in patients is caused by C. difficile, and added that it reoccurs in about 20 percent of those patients because of antibiotic treatment.
Genzyme, of Cambridge, Mass., noted that CDAD's occurrence has increased in recent years.
"They'll initially receive the drug while in a hospital or nursing home," Olson said. "But a good portion of them are released back to their home. They would continue treatment through our proposed 14 days of therapy."
Tolevamer is designed to bind to and remove toxins released by C. difficile that damage the intestine. Its Phase III program will involve more than 1,000 patients at more than 250 sites. Actually comprising two studies - one has North American facilities and the other European and Australian locations - the trials eventually will generate data to support applications to both the FDA and European authorities. Enrollment is expected to take about 18 months.
The primary endpoint will assess its non-inferiority to the standard prescribed oral dose of the antibiotic vancomycin, measured by the percent of patients with resolution of CDAD. The studies also will evaluate tolevamer against metronidazole, another antibiotic for CDAD. Lastly, to test tolevamer's ability to reduce the number of CDAD recurrences, the trials are designed to measure its capability in that regard against both vancomycin and metronidazole.
Phase II data showed that tolevamer was not inferior to vancomycin, and both products were found to be similar in median days to resolution of the infection.
The Phase III study will follow a randomized 2:1:1 ratio in a double-blinded format, and half of those enrolled will receive 9 grams of daily tolevamer in a new liquid formulation.
Genzyme owns all rights to the drug and has internally funded all of its development to date. Olson said other non-antibiotic approaches to treat CDAD include probiotic products, which do not fall under the regulatory oversight of the FDA, and a still-investigational injectable vaccine in development at a state lab in Massachusetts.
Tolevamer stems from the same technology platform that produced the polymer Renagel (sevelamer hydrochloride), a phosphate binder approved for end-stage renal disease. An out-licensed polymer-based therapy also from that technology platform, WelChol (colesevelam hydrochloride, from Sankyo Pharma Inc.), is for cholesterol.
Other late-stage drug development programs of note at Genzyme include Myozyme (alglucosidase alfa), which has been developed for Pompe disease. The company already has filed for its European approval and expects to submit an application to the FDA around the middle of this year. Other ongoing activities include post-marketing studies or trials geared toward label expansions, such as a U.S.-based pivotal trial of Synvisc (hylan G-F 20) to treat pain due to osteoarthritis of the hip. It already is approved to treat pain due to osteoarthritis of the knee.
On Monday, Genzyme's shares (NASDAQ:GENZ) rose 12 cents to close at $56.11.