First Phase 3 Study Of Tolevamer In Patients With C. Difficile Associated Diarrhea

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C. Difficile Associated Diarrhea

Clinical studies to assess the safety and efficacy of tolevamer liquid, an investigational, non-antibiotic, polymer therapy for patients with Clostridium difficile associated diarrhea.

The second Phase 3 study of tolevamer liquid is fully enrolled and results are expected later this year.

In this first Phase 3 study known as the Polymer Alternative for CDAD Treatment (PACT) study, tolevamer liquid did not meet its primary endpoint of non-inferiority to the standard prescribed oral dose of the antibiotic vancomycin, as measured by the percent of patients with resolution of CDAD. This result contrasts with the findings from Genzyme's earlier Phase 2 study of a solid oral dosage formulation of tolevamer that met its primary endpoint of non-inferiority compared to vancomycin.

Consistent with recent published studies, high rates of CDAD recurrences were observed in patients treated with either vancomycin or metronidazole. High CDAD recurrence rates were not observed in patients treated with tolevamer liquid. Tolevamer liquid was generally well tolerated with no unanticipated safety concerns. Data from this first Phase 3 study is expected to be presented at a future medical conference.

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"These are disappointing results that alter our expectations about the potential for commercializing tolevamer in the near future," stated Henri A. Termeer, chairman and chief executive officer of Genzyme Corp. "The results of our second Phase 3 study will be available later this year and will help us determine what contribution tolevamer might be able to make in addressing this serious unmet medical need."

C. difficile has become one of the most significant infection control concerns in healthcare today. Physicians worldwide are confronting a worsening epidemic, with an alarming rise in the incidence of disease, higher numbers of patients with complications and more frequent failures of standard antibiotic therapy.

Tolevamer is designed to bind and neutralize the 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.

The PACT study, which involved more than 1,100 patients at approximately 300 sites in North America, Europe, and Australia, is the largest of its kind ever to be conducted for CDAD. In this trial, tolevamer was compared to metronidazole and vancomycin. Aside from testing tolevamer's efficacy, this was also the first large, rigorously designed, multi-center clinical study that will compare the efficacy of the current standards of care.

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.

Earlier studies have shown that even after successful treatment with the current standard of care, approximately 20 percent of patients experience a recurrence of CDAD potentially requiring repeat hospitalization. In addition, a subset of patients with CDAD develop multiple recurrences of the disease, with symptoms that may persist for years.

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