New England Journal publishes fidaxomicin Phase 3 trial results against CDI

Feb 3 2011

Optimer Pharmaceuticals, Inc. announced The New England Journal of Medicine has published results from the North American Phase 3 trial evaluating the safety and efficacy of the Company's novel antibiotic fidaxomicin as a treatment for patients with Clostridium difficile infection (CDI). The Phase 3 trial showed that fidaxomicin significantly reduced recurrence rates and increased global cure rates when compared to vancomycin, the only treatment approved by the U.S. Food and Drug Administration for CDI. The article titled, "Fidaxomicin versus Vancomycin for Clostridium difficile Infection," appears in the February 3, 2011 issue of The New England Journal of Medicine.

A multi-media news release containing video is available at the following link:  http://multivu.prnewswire.com/mnr/optimerpharma/47526/

"C. difficile has surpassed MRSA as a source for hospital acquired infection, and is associated with severe illness and death. More alarming, 20-30% of patients treated with current antibiotics will relapse," said Sherwood L. Gorbach, M.D., co-author and Optimer's Chief Medical Officer. "Data published in The New England Journal of Medicine shows that fidaxomicin not only maintained the high cure rate expected of vancomycin, but also demonstrated a 45% reduction in recurrences. Reduction in the rate of recurrence is a critical advancement for one of the most problematic aspects of CDI.  Fidaxomicin may represent a significant advance for physicians and hospitals to provide an effective treatment for patients with CDI.  At a time when our population is aging --the first of the baby boomers turned 65 in January – we welcome this innovation to treat CDI, in which the elderly are at particular risk."

The results published in The New England Journal of Medicine showed that patients treated with fidaxomicin experienced a significant reduction in rate of recurrence of CDI compared with patients treated with vancomycin (13.3% vs. 24.0%).

"These results showed that recurrence of CDI is significantly less likely to occur following treatment with fidaxomicin versus vancomycin. By lowering recurrences, fidaxomicin would eliminate the costs of treating additional CDI episodes and potentially reduce the spread of the disease, which may result in a lower cost burden to the healthcare system," said lead author, Thomas J. Louie, M.D., Medical Director, Infection Prevention and Control for the Calgary Health Region and professor in the Departments of Medicine and Microbiology-Infectious Diseases, University of Calgary.

"Fidaxomicin is minimally absorbed in the intestinal tract, which means it stays in the gut where C. difficile resides. Fidaxomicin is also a narrow spectrum antibiotic, meaning that it acts selectively on C. difficile with minimal disruption to the healthy, protective bacteria in the gut," said Mark Miller, M.D., FRCPC, a co-author on the paper and Chief of the Department of Microbiology, Head of Infectious Diseases Division and Chair of Infection Prevention and Control Committee, Jewish General Hospital in Montreal. "The ability of this antibiotic to stay in the gut and act primarily on the bacteria inflicting damage may be key reasons why we saw a significant reduction in the rate of CDI recurrences in the clinical trial."

Fidaxomicin Clinical Study Design

The Phase 3 trial was a multi-center, randomized, double-blind clinical trial, which enrolled 629 adult subjects. Subjects with confirmed CDI received either 200 mg fidaxomicin dosed orally twice daily or 125 mg Vancocin® (vancomycin hydrochloride capsules, USP) dosed orally four times daily.  This study was conducted in approximately 100 clinical sites throughout North America.  The objective of the study was to show that a 10-day course of fidaxomicin was at least as efficacious (non-inferior) and safe as a 10-day course of Vancocin for the treatment of CDI.  Non-inferiority in clinical cure (defined as patients requiring no further CDI therapy two days after completion of study medication) compared to Vancocin was the primary endpoint.  If cured, subjects were monitored for a subsequent four-week period to evaluate recurrence, which was a secondary endpoint.  Global cure, an exploratory endpoint, was defined as patients who were cured and did not have a recurrence during this subsequent four-week period.  The modified Intent-to-Treat Population (mITT) is the patient group with CDI confirmed by diarrhea with a positive toxin assay and received at least one dose of study medication.  The per protocol Population is the patient group with CDI confirmed by diarrhea with a positive toxin assay, that met all inclusion and exclusion criteria, and that received at least 3 days of therapy if deemed a failure or at least 8 days of therapy if deemed a cure.