Clinical Infectious Diseases Publishes Subgroup Analysis Showing Optimer’s DIFICID(TM) (fidaxomicin) Tablets Exhibited Higher Clinical Cure and Global Cure Rates Than Vancomycin in Patients with Clostridium difficile-Associated Diarrhea (CDAD) Receiving C
SAN DIEGO, Aug. 16, 2011 /PRNewswire/ — Optimer Pharmaceuticals, Inc. (NASDAQ: OPTR) announced today that a subgroup analysis of patients receiving concomitant systemic antibiotics in two Phase 3 clinical trials exploring the use of DIFICID(TM) (fidaxomicin) tablets in the treatment of adult patients with Clostridium difficile-associated diarrhea (CDAD) was published online in the September 1 issue of Clinical Infectious Diseases (CID). The analysis found that in the presence of concomitant systemic antibiotic therapy, which is the use of antibiotics to treat concurrent infections, DIFICID achieved a significantly higher initial clinical cure rate, and higher rate of global cure, compared to oral vancomycin. In the article, approximately 28% of patients in the Phase 3 clinical trials required antibiotic treatment for concurrent infections, primarily lung and urinary tract, and these treatments had an adverse impact on the efficacy of both CDAD therapies.
Patients with CDAD who received DIFICID while taking concomitant antibiotics demonstrated a significantly higher clinical cure rate of CDAD than patients who received oral vancomycin and concomitant antibiotics (90.0% clinical cure rate vs. 79.4%, respectively; p=0.04).Regardless of concomitant antibiotic use, DIFICID was also statistically superior to oral vancomycin in global cure rate. Global cure is defined as clinical cure with no recurrence through the end of study visit 26 to 30 days after completion of CDAD treatment.
“To date, there has been little research demonstrating the impact of concomitant antibiotic use in patients being treated for CDAD,” said Dr. Kathleen Mullane, Associate Professor of Medicine at The University of Chicago Department of Medicine and an author on the study. “Results from this subgroup analysis show that more than one in four patients with CDAD were also taking concomitant antibiotics for other infections and that concomitant antibiotic therapy can significantly compromise CDAD treatment. The results also suggest that DIFICID may help blunt the effect of concomitant antibiotics on response to CDAD treatment and that continued investigation of the impact of concomitant antibiotic use in this patient population is warranted.”
Effect of Concomitant Antibiotic Use on Clinical Outcomes
Among patients analyzed in the study, the use of concomitant antibiotics compromised response to CDAD therapy. For the combined DIFICID and vancomycin treatment groups, CDAD patients who received concomitant antibiotics had clinical cure rates of 84.4%, compared to cure rates of 92.6% among patients who did not (p<0.001), and experienced a median extended time to resolution of diarrhea of 97 hours compared to 54 hours in patients who did not receive additional antibiotics (p<0.001). Global cure was observed in 74.7% of patients who did not receive concomitant antibiotics compared to 65.8% of patients receiving concomitants antibiotics at any time during the study (p= 0.005). Use of concomitant antibiotics tended to increase the rate of recurrence but did not reach significance.
Effect of DIFICID vs. Vancomycin with Concomitant Antibiotics
In the absence of concomitant antibiotic use, DIFICID and vancomycin were similar in achievement of clinical cure by the end of treatment (92.3% vs. 92.8%; p= 0.80). However, when patients received one or more antibiotics concurrently with study drug, DIFICID was superior to vancomycin in achieving clinical cure (90.0% vs. 79.4% p = 0.04). When patients received no additional antibiotics at any time during the study, the global cure rate was 80.8% for DIFICID patients and 69.1% for vancomycin patients(p < 0.001). Global cure rates were substantially reduced in both treatment groups when patients received concomitant antibiotics at any time, but 72.7% of DIFICID patients achieved global cure compared to 59.4% for vancomycin (p = 0.02). Concomitant antibiotic use was associated with higher recurrence rates in both the DIFICID and oral vancomycin treatment groups. However, recurrence was consistently less frequent following DIFICID treatment whether patients received concomitant antibiotics or not. In patients receiving concomitant antibiotics at any time during treatment or follow-up, treatment with DIFICID was associated with a recurrence rate of 16.9% compared to 29.2% with oral vancomycin (p=0.048).
“Medical guidelines recommend discontinuation of concomitant antibiotics at the diagnosis of CDAD if possible. However, that may not always be practical because patients need the antibiotics for serious concurrent infections,” said Dr. Sherwood Gorbach, Chief Scientific Officer at Optimer and an author on the study. “To the extent treatments for CDAD can help mitigate the adverse impact of concomitant antibiotics on response to treatment, they would offer a much needed treatment option for this patient population.”
Additional Study Details
Patients from two prospective, double-blind, randomized, noninferiority Phase 3 studies evaluating DIFICID and oral vancomycin in the treatment of CDAD were pooled for the subgroup analysis.
Of the 999 evaluable patients in the combined prospective studies, 275 patients (27.5%) received concomitant antibiotic therapy at some time during the treatment or follow-up course. Researchers analyzed the effect of concomitant antibiotic use on response rates for clinical cure, recurrence and global cure in CDAD patients, as well as compared the effects of DIFICID and oral vancomycin in the treatment of CDAD patients receiving concomitant antibiotics.
Patients were randomized to receive DIFICID (200 mg twice daily) or oral vancomycin (125 mg four times daily) for 10 days. If patients achieved clinical cure, they were followed for recurrence for 4 weeks. Patients were considered to have taken concomitant antibiotics if they received one or more oral or IV doses of antibiotics during the treatment or follow-up periods. Eligible patients had received a diagnosis of first episode of CDAD or a first recurrence of CDAD within the previous three months and had received no more than 24 hours of pretreatment with vancomycin or metronidazole. Treatment with other therapies potentially effective for CDAD, such as oral bacitracin, fusidic acid and rifaximin were not allowed. Topical antibiotics, treatments for CDAD and antifungal and antiviral agents with no antibacterial activity were not included as concomitant antibiotics. Patients were excluded if diagnosed with immediately life-threatening CDAD.
Clinical cure was defined as resolution of diarrhea (less than or equal to three unformed stools for two consecutive days) maintained until the end of therapy and for two days afterward. Recurrence was defined as the reappearance of symptoms of CDAD within four weeks after completing treatment, the presence of C. difficile toxin A, toxin B, or both in stool, and the need for retreatment. Global cure was defined as clinical cure with no recurrence during the follow-up period.
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.
Current estimates suggest CDAD may affect more than 700,000 people in the U.S. each year, though the incidence may be higher as many cases are believed to be undiagnosed, untreated and underreported. The disease adds significant costs and burden to the U.S. healthcare system with estimates for medical treatment and hospital stays associated with CDAD reaching as much as $3.8 billion every year. Historically, approximately 20% to 30% of CDAD patients who initially respond to treatment experience a clinical recurrence.
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(TM) (fidaxomicin) tablets, an FDA-approved antibacterial drug for the treatment of adult patients 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(TM), a product in the fluoroquinolone class of antibiotics that has completed Phase 3 trials as a treatment for infectious diarrhea. 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 DIFICID’s ability to mitigate the impact of concomitant antibiotics on response to CDAD treatment. 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: Optimer’s ability to commercialize DIFICID, whether healthcare professionals will prescribe DIFICID, whether DIFICID will receive reimbursement coverage from healthcare payors and government agencies, the extent to which DIFICID will be accepted on hospital formularies and other risks detailed in Optimer’s filings with the Securities and Exchange Commission.
Optimer Pharmaceuticals, Inc.
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