Optimer Announces Presentation of Additional Data From Fidaxomicin Phase 3 Study for the Treatment of Clostridium Difficile Infection (CDI)
Fidaxomicin Significantly Less Likely than Vancomycin to Promote VRE Colonization
SAN DIEGO, Sept. 15 /PRNewswire-FirstCall/ -- Optimer Pharmaceuticals, Inc. (NASDAQ:OPTR) today announced that new data highlighting fidaxomicin's (OPT-80) lower CDI recurrence rates and reduced risk of vancomycin-resistant enterococci (VRE) acquisition from Optimer's North American phase 3 study were presented at the 49th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in San Francisco.
"The additional data highlight fidaxomicin's unique profile as a new antibiotic class with beneficial characteristics for treating CDI," said Michael N. Chang, Ph.D., President and CEO of Optimer Pharmaceuticals. "These analyses describe fidaxomicin's low recurrence rate, safety profile, potent activity against CDI, and minimal disruption to the normal intestinal flora. We think fidaxomicin has the potential to be the treatment of choice for CDI which is a serious unmet medical need with limited treatment options."
Yoav Golan, M.D., an investigator from the Tufts Medical Center in Boston, MA, presented additional analyses around the previously reported recurrence data showing that patients treated with fidaxomicin had a substantially lower recurrence rate (13.3%) than those treated with vancomycin (24.0%). However, the recurrence rate difference between fidaxomicin and vancomycin was even greater, 10.9% versus 24.3%, respectively, in patients who did not receive CDI therapy (either vancomycin or metronidazole) in the 24-hour pre-trial enrollment period. Dr. Golan further noted that CDI recurrence occurred significantly later in patients treated with fidaxomicin with only 3% and 9% recurrence rates respectively, versus 14% and 20% recurrence rates for vancomycin, respectively, at 10 and 20 days post-treatment.
In an oral presentation, Curtis J. Donskey, M.D., an investigator from the Cleveland VA Medical Center in Ohio, concluded that fidaxomicin is less likely than vancomycin to promote acquisition of VRE colonization in patients treated for CDI, likely due to inhibitory activity of fidaxomicin against many VRE strains and fidaxomicin's relative sparing of the intestinal flora including Bacteroides spp. The results showed that only 7% of patients treated with fidaxomicin acquired VRE versus 31% of vancomycin treated patients (p<0.001) from among a subset of 302 CDI patients, 248 of whom had a negative VRE stool sample upon entering the Phase 3 trial. In addition, 63% of the patients treated with fidaxomicin were found to retain greater than 100,000 Bacteroides bacteria per gram of stool versus only 13% of the vancomycin treated patients (p=0.004). These results provide further evidence that unlike vancomycin, fidaxomicin does not suppress Bacteroides bacteria, which is a major component of the intestinal flora and prevents C. difficile overgrowth. The Bacteroides sparing effect of fidaxomicin could be one of the reasons for the lower recurrence rate observed in the Phase 3 trial.
Detailed strain typing results from the phase 3 trial presented by Dale N. Gerding, M.D., from the Hines VA Hospital in Chicago, IL, identified the various strain type groups in the study. These data show that the overall cure rate among patients harboring BI isolates is significantly lower than those with non-BI strains (85.4% vs. 95.5% p=.004). Fidaxomicin and vancomycin had comparable cure rates against both BI and non-BI strains. The recurrence rates in the BI/NAP1/027 group, 36% of the patients analyzed, were similar between fidaxomicin and vancomycin. In the non-BI/NAP1/027 groups, 64% of the patients analyzed, patients treated with fidaxomicin had only a 7.8% (8/103) recurrence rate versus a 25.5% (27/106) recurrence rate for the vancomycin treated patients.
Pam Sears, Ph.D., from Optimer Pharmaceuticals, presented results from the phase 3 study showing that there is minimal systemic absorption of fidaxomicin with all post-dose plasma measurements in the nanogram range. At the same time, the average fecal drug levels were greater than 5,000 times fidaxomicin's MIC(90) against C difficile. These results indicate that fidaxomicin has a favorable pharmacokinetic profile for the treatment of CDI.
Optimer's Chief Medical Officer, Sherwood L. Gorbach, M.D., presented safety results from the first phase 3 study, which show that fidaxomicin has a safety profile comparable to that of vancomycin for the treatment of CDI. Subjects from the two treatment arms had similar adverse events and serious adverse events, as well as cardiologic and clinical laboratory profiles while on study. All-cause mortality was 5.3% for fidaxomicin versus 6.5% for vancomycin.
Ellie J. Goldstein, M.D., from the R.M. Alden Research Laboratory in Santa Monica, CA, presented the antimicrobial susceptibilities of fidaxomicin, vancomycin, metronidazole, and rifaximin to C. difficile cultured from fecal specimens collected from patients at study entry and at failure/recurrence. The data showed that the susceptibility (MIC(90)) of baseline isolates did not predict clinical cure, failure, or recurrence for either fidaxomicin or vancomycin. No resistance to either fidaxomicin or vancomycin developed during the phase 3 study. Furthermore, two of the C. difficile strain typing groups, the BI and K group strains had lower susceptibilities than other groups to rifaximin and metronidazole with resistance to rifaximin occurring in 14% of the BI group and 18% of the K group.
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Fidaxomicin Clinical Study Design
629 adult subjects were enrolled in this multi-center, randomized, double-blind phase 3 clinical trial, which was the largest such trial for the treatment of CDI. Subjects with confirmed CDI received either 200 mg fidaxomicin dosed orally twice daily or 125 mg Vancocin dosed orally four times daily. This study was conducted in more than 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 (vancomycin hydrochloride capsules, USP) for the treatment of CDI.
The primary endpoint of the study was clinical cure defined as patients requiring no further CDI therapy two days after completion of study medication, as determined by the investigator. The secondary endpoint evaluated CDI recurrence up to four weeks post therapy with recurrence defined as the return of diarrhea associated with CDI confirmed by a positive toxin test. Global cure was defined as patients who were cured and did not have a recurrence.
About Clostridium Difficile Infection
CDI has become a growing problem in hospitals, long-term care facilities and in the community. It is a serious illness caused by 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. CDI typically develops from the use of broad-spectrum antibiotics that disrupt normal gastrointestinal (gut) flora, allowing C. difficile bacteria to flourish.
Current therapeutic options for CDI include metronidazole and oral vancomycin. However, approximately 20% to 30% of CDI patients who initially respond to these treatments experience a clinical recurrence following cessation of antibiotic administration.
Primary risk factors for CDI include broad-spectrum antibiotic use, advanced age (over 65), emerging hyper-virulent strains (BI /NAP1/027, 078, 001) of C. difficile, and previous exposure to CDI that lead to recurrence. Higher incidence, increased treatment failures, and recurrence with standard therapies have resulted in greater awareness and concern of CDI among medical professionals and public health officials.
About Fidaxomicin (OPT-80)
Fidaxomicin is the first in a new class of antibiotics called macrocyclics, which inhibit the bacterial enzyme RNA polymerase, resulting in the death of Clostridium difficile. The narrow spectrum profile of fidaxomicin may eradicate Clostridium difficile selectively with minimal disruption to the normal intestinal flora. This may facilitate the return of the normal physiological conditions in the colon and reduce the probability of CDI recurrence.
About Optimer Pharmaceuticals
Optimer Pharmaceuticals, Inc. is a biopharmaceutical company focused on discovering, developing and commercializing innovative anti-infective products to treat serious infections and address unmet medical needs. Optimer has two late-stage anti-infective product candidates under development. Fidaxomicin, formerly known as OPT-80, is the only antibiotic therapy currently in phase 3 worldwide clinical development for Clostridium difficile infection. Prulifloxacin is an antibiotic which has completed two phase 3 clinical trials for the treatment of travelers' diarrhea, a form of infectious diarrhea. Additional information can be found at http://www.optimerpharma.com/.
Statements included in this press release that are not a description of historical facts are forward-looking statements, including without limitation all statements related to the ability of fidaxomicin to treat CDI and address current treatment limitations. Words such as "believes," "anticipates," "plans," "expects," "intend," "will," "goal" 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. 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 timing, progress and likelihood of success of its product research and development programs, the timing and status of its preclinical and clinical development of potential drugs and other risks detailed in Optimer's filings with the Securities and Exchange Commission.
Contacts Optimer Pharmaceuticals, Inc. John Prunty, CFO & VP, Finance Christina Donaghy, Corporate Communications Manager 858-909-0736 Porter Novelli Life Sciences Jason I. Spark, Vice President 619-849-6005
Source: Optimer Pharmaceuticals, Inc.
CONTACT: John Prunty, CFO & VP, Finance, or Christina
Communications Manager, both of Optimer Pharmaceuticals, Inc.,
+1-858-909-0736; or Jason I. Spark, Vice President of Porter Novelli Life
Sciences, +1-619-849-6005, for Optimer Pharmaceuticals, Inc.
Web Site: http://www.optimerpharma.com/
Posted: September 2009