New Analysis Shows Age has a Significant Effect on Outcomes in Patients Being Treated for Clostridium difficile Infection (CDI)
by PR Newswire
JERSEY CITY, N.J., Feb. 14, 2013 /PRNewswire/ -- Optimer Pharmaceuticals, Inc. (Nasdaq: OPTR) today announced that the February 2013Journal of the American Geriatrics Society published results from a multivariate analysis demonstrating that advancing age is a predictor of deterioration in treatment outcomes in patients with Clostridium difficile infection (CDI). The analysis was performed using data from two large, randomized Phase 3 clinical studies that compared the efficacy of DIFICID® (fidaxomicin) tablets to vancomycin for the treatment of CDI. The new analysis predicts that with each decade increase after the age of 40, rates of clinical cure and sustained clinical response decrease by 17% and 13% with treatment, respectively, per decade (OR=0.83, 95% CI [0.72, 0.95], p=0.008; and OR=0.87, 95% CI [0.79, 0.94], p<0.001), while rates of disease recurrence increase by 17% (OR=1.17, 95% CI [1.04, 1.30], p=0.007).
Results of the analysis showed that DIFICID and vancomycin were comparably effective in attaining clinical cure in all age groups studied; in those younger than 40 years of age, clinical cure was achieved in 97.2% of patients and in those older than 80, clinical cure was achieved in 87.5% to 88.2% of patients. For patients who achieved clinical cure, DIFICID-treated patients were half as likely to have had a recurrence compared to patients treated with vancomycin (OR=0.46, 95% CI [0.32, 0.67], p<0.001). The analysis showed the probability of sustained clinical response nearly doubled among DIFICID-treated patients compared to patients who received vancomycin (OR=1.86, 95% CI [1.40, 2.47], p<0.001). When researchers conducted an analysis adjusting for age and other factors that may impact treatment outcome, including the administration of concomitant antibiotics and C. difficile strain, DIFICID was associated with a 60% lower risk of recurrence (p<0.001) compared to vancomycin.
"This analysis reinforces the serious consequences of CDI for patients as they get older, including significantly increased risk of disease recurrence and treatment failure, " said Sherwood L. Gorbach, M.D., co-author and Optimer's Chief Scientific Officer and Senior Vice President. "Most notably, results showed that the decline in treatment outcomes can begin as early as age 40, which suggests that age is an important risk factor for patients."
About the Analysis
The analysis was based on two multi-center, randomized, double-blind Phase 3 clinical trials, which enrolled 1,164 adult patients throughout Europe and North America. Patients with confirmed CDI, received either 200 mg of DIFICID (fidaxomicin) tablets dosed orally twice daily or 125 mg of vancomycin dosed orally four times daily for 10 days.
CDI was defined by a change in bowel habits, with more than three unformed bowel movements (or >200 mL unformed stool for patients with rectal collection devices) in the 24 hours before randomization, and the presence of either toxin A or B of C. difficile in the stool within 48 hours of randomization. The primary endpoint of the study was non-inferiority in clinical cure, which was defined as resolution of diarrhea (no more than three unformed stools for two consecutive days) maintained until the end of therapy for two days after. Patients who achieved a clinical cure were monitored for a subsequent four-week period to evaluate recurrence, which was a secondary endpoint. Sustained clinical response, an additional endpoint, was defined as patients who achieved clinical cure and did not experience a recurrence of symptomatic CDI by the end-of-study visit. The modified intent-to-treat population (mITT) was comprised of patients with documented CDI who received at least one dose of study medication (n=1,105). The per protocol population was comprised of patients in the mITT group with at least three days of treatment (for failure) or at least eight days of treatment (for cure), documented adherence to protocol, and an end-of-therapy evaluation (n=999).
Researchers used logistic regression models (SAS, Cary, NC) to test the effects of age, study (NCT00314951 or NCT00468728) and treatment group (DIFICID or vancomycin) on clinical cure, sustained clinical response and disease recurrence. Patient data was stratified as inclusive age categories: <40, 41-50, 51-60, 61-70, 71-80 and >80 years. The relationship of age or treatment group to clinical cure, sustained clinical response and disease recurrence was determined using Chi-square tests. Odds ratios, 95% confidence intervals and P values were determined. A P value of <0.05 was considered significant. Multiple regression analysis of all other risk factors found to have a statistically significant association (p< 0.1) to outcomes was performed.
About Clostridium difficile Infection (CDI)
Clostridium difficile infection (CDI) 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. Clostridium difficile-associated diarrhea is the most common symptom of CDI. In recent years, C. difficile has surpassed methicillin-resistant Staphylococcus aureus (MRSA) as the leading cause of healthcare-acquired infections in community hospitals. Patients typically develop CDAD from the use of broad-spectrum antibiotics that disrupt normal gastrointestinal (gut) flora, possibly allowing C. difficile bacteria to flourish.
About DIFICID® (fidaxomicin) Tablets
DIFICID is the first macrolide antibacterial drug indicated for Clostridium difficile-associated diarrhea (CDAD) to be approved in over 25 years in the U.S. It is indicated for the treatment of CDAD in adults 18 years of age or older. DIFICID is administered in 200 milligram tablets given orally twice daily.
Important Safety Information for DIFICID
DIFICID is contraindicated in patients with hypersensitivity to fidaxomicin or to any of the excipients in the formulation. DIFICID should not be used for systemic infections. Only use DIFICID for infection proven or strongly suspected to be caused by C. difficile. Prescribing DIFICID in the absence of a proven or strongly suspected C. difficile infection is unlikely to provide benefit to the patient and increases the risk of the development of drug resistant bacteria. The most common adverse reactions are nausea (11%), vomiting (7%), abdominal pain (6%), gastrointestinal hemorrhage (4%), anemia (2%) and neutropenia (2%).
About Optimer Pharmaceuticals
Optimer Pharmaceuticals, Inc. (NASDAQ: OPTR) is a global biopharmaceutical company focused on developing and commercializing innovative hospital specialty products that have a positive impact on society. Optimer developed DIFICID® (fidaxomicin) tablets, an FDA-approved macrolide antibacterial drug for the treatment of Clostridium difficile-associated diarrhea (CDAD) in adults 18 years of age and older and is commercializing DIFICID in the U.S. and Canada. Optimer also received marketing authorization for fidaxomicin tablets in the European Union where its partner, Astellas Pharma Europe, is commercializing fidaxomicin under the trade name DIFICLIR™. The Company is exploring marketing authorization in other parts of the world where C. difficile has emerged as a serious health problem, including Asia. Additional information can be found at http://www.optimerpharma.com.
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 potential benefits of DIFICID in treating certain patients and the risk, impact and burden 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: the possibility of alternative means of preventing or treating CDAD, whether Optimer will conduct additional clinical trials with respect to DIFICID or whether any such trials will be successful, 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.
Optimer Pharmaceuticals, Inc.
David Walsey, Vice President, Investor Relations and Corporate Communications
Canale Communications, Inc.
Jason I. Spark, Senior Vice President
SOURCE Optimer Pharmaceuticals, Inc.