DIFICID Demonstrated Early Superiority in the First 12 Days Compared to Vancomycin in New Analysis of Phase 3 Study Results
- Results included in late-breaker session at the IDSA Annual Meeting -
SAN DIEGO, Oct. 20, 2011 /PRNewswire/ -- Optimer Pharmaceuticals, Inc. (Nasdaq: OPTR) announced today that data being presented at the 49th Annual Meeting of the Infectious Diseases Society of America (IDSA) demonstrate that patients treated with DIFICID™ (fidaxomicin) tablets for Clostridium difficile-associated diarrhea (CDAD) experienced faster resolution of diarrhea and lower risk of death during the first 12 days following initiation of treatment compared to patients treated with vancomycin. The retrospective analysis of results from two large, multi-national Phase 3 clinical studies, which assessed the efficacy of DIFICID versus vancomycin for the treatment of CDAD in adults, was completed by researchers from the National Institute for Health Research (NIHR) Biomedical Research Centre, Oxford, a research partnership between the Oxford Radcliffe Hospitals and the University of Oxford.
In the analysis, patients treated with DIFICID experienced a 37% reduction in persistent diarrhea or death through day 12 of the study (95% CI: 2-60%; p=0.037) compared to those treated with vancomycin. These data are among those featured in a late-breaking poster presentation at the IDSA annual meeting being held in Boston from October 20-23.
"We were encouraged by the results of the Phase 3 clinical studies and believed that a more comprehensive look at the patient characteristics of the Phase 3 study participants might yield even greater insights into the use of DIFICID for the treatment of CDAD," said Sarah Walker, PhD, Senior Statistician at the NIHR Biomedical Research Centre, Oxford, and the primary author of the analysis. "In our analysis, we found that DIFICID not only reduced persistent diarrhea and early deaths in patients within the first 12 days following initiation of treatment but also significantly reduced persistent diarrhea, disease recurrence or death through day 40 of the study."
The analysis was independently funded by the NIHR Biomedical Research Centre, Oxford, a research partnership between the Oxford Radcliffe Hospitals and the University of Oxford.
The analysis was performed using data from two prospective, randomized, double-blinded, non-inferiority Phase 3 studies evaluating DIFICID and oral vancomycin in the treatment of CDAD in adults 18 years of age or older. A non-inferiority design was utilized to demonstrate the efficacy of DIFICID (200 mg orally twice daily for 10 days) compared to vancomycin (125 mg orally four times daily for 10 days) in adults with CDAD. The studies enrolled a total of 1,164 adults with confirmed CDAD. The primary objective of both studies was to show that a 10-day course of DIFICID was as effective as oral vancomycin in achieving a clinical cure at the end of therapy. Clinical cure was defined as resolution of diarrhea (no more than 3 unformed stools for 2 consecutive days) maintained for the duration of therapy with no further requirement for therapy assessed two days after the end of the 10 day treatment. Subjects meeting the criteria for clinical cure were followed for 28 days after the end of treatment (36-40 days after randomization) and assessed for the additional efficacy endpoints of recurrence and global cure. Recurrence was defined by the reappearance of more than 3 unformed stools in any 24-hour period with C. difficile toxin A or B or both detected and a need for retreatment. Global cure was defined as clinical cure without recurrence.
To compile the results, researchers conducted a post-hoc exploratory analysis to determine the time-to-event for a composite endpoint of persistent diarrhea, disease recurrence or death of the combined intent-to-treat (ITT) population from the two randomized Phase 3 studies. Researchers used fixed-effects meta-analysis and Cox regression models to complete the analysis, fixing the time of the 8-12 day primary end of therapy assessment utilized in the clinical trials at 12 days.
Additional Study Results
In the two Phase 3 studies, DIFICID achieved clinical cure rates at the end of treatment that were non-inferior to oral vancomycin and lower recurrence rates that were statistically significant. In the ITT analysis, the superior reduction in persistent diarrhea or death seen at day 12 for DIFICID (p=0.037) was driven by 7 deaths among DIFICID-treated patients (1.2%) compared to 17 (2.9%) deaths among patients who received vancomycin (exact p=0.06). The overall analysis demonstrated a 40% reduction in persistent diarrhea, disease recurrence or death (all causes) compared to vancomycin through day 40 of the study (95% CI: 26-51%; p<0.0001).
Results of the ITT combined analysis also show that randomization to DIFICID in the Phase 3 clinical studies reduced the risk of persistent diarrhea, recurrence or death by 52% (95% CI: 37-63%; p<0.0001), even after adjusting for other factors. Persistent diarrhea or death in the first 12 days following initiation of treatment was most strongly predicted by previous anti-CDAD antibiotic use in the 24 hours prior to randomization (p=0.0001) and low baseline eosinophils (p=0.007) and/or albumin (p<0.0001) at randomization. Patients with CDAD in the three months prior to entering the study had a 68% higher risk of recurrence or death during study days 13-40. Through 40 days, there was no evidence that the benefits of DIFICID over vancomycin varied according to disease severity, prior history of CDAD, previous anti-CDAD antibiotics, inpatient versus outpatient, patient age, baseline albumin or baseline creatinine levels.
Clostridium difficile-associated diarrhea (CDAD) has become a significant medical problem in hospitals, long-term care facilities and in the community. CDAD is a serious illness resulting from infection of the inner lining of the colon by C. difficile bacteria, which produce toxins that cause inflammation of the colon, severe diarrhea and, in the most serious cases, death. Patients typically develop CDAD from the use of broad-spectrum antibiotics that disrupt normal gastrointestinal (gut) flora, possibly allowing C. difficile bacteria to flourish. Older patients in particular are at risk for CDAD, potentially because of a weakened immune system or the presence of underlying disease. Approximately two-thirds of CDAD patients are 65 years of age or older. Historically, approximately 20% to 30% of CDAD patients who initially respond to treatment experience a clinical recurrence.
The 49th Annual Meeting of the Infectious Diseases Society of America (IDSA) brings together physicians, scientists, and other health care professionals involved in research, patient care, public health, disease prevention, and education in the field of infectious diseases. The meeting showcases the latest news in the field of infectious diseases with emphasis on contemporary trends, including emerging infections, new diagnostic and therapeutic advances. IDSA 2011 takes place October 20-23 at the Boston Exhibition and Convention Center in Boston, Massachusetts.
Optimer Pharmaceuticals, Inc. is a biopharmaceutical company focused on discovering, developing and commercializing innovative hospital specialty products that have a positive impact on society. Optimer has developed and commercialized DIFICID™ (fidaxomicin) tablets, an FDA-approved antibacterial drug for the treatment of adults 18 years of age or older with Clostridium difficile-associated diarrhea (CDAD). Optimer has filed a marketing authorization application with the European Medicines Agency for fidaxomicin. Optimer's clinical pipeline includes Pruvel™, a product in the fluoroquinolone class of antibiotics that has completed Phase 3 trials as a treatment for infectious diarrhea.
Forward Looking Statements
Statements included in this press release that are not a description of historical facts are forward-looking statements, including without limitation statements related to the DIFICID's potential as a treatment for CDAD compared to other therapies and the incidence and costs of CDAD. Words such as "believes", "would", "anticipates", "plans", "expects", "may", "intend", "will", and similar expressions are intended to identify forward-looking statements. The inclusion of forward-looking statements should not be regarded as a representation by Optimer that any of its plans will be achieved. These forward-looking statements are based on management's expectations on the date of this release. Actual results may differ materially from those set forth in this release due to the risks and uncertainties inherent in Optimer's business including, without limitation, risks relating to: whether healthcare professionals will prescribe DIFICID, the extent to which DIFICID will be accepted on hospital formularies, the development of alternative means of preventing or treating DIFICID, and other risks detailed in Optimer's filings with the Securities and Exchange Commission. Forward-looking statements speak only as of the date of this release, and Optimer undertakes no obligation to update or revise these statements, except as may be required by law.
Posted: October 2011