Salix Pharmaceuticals, Ltd. (NASDAQ:SLXP) today announced the presentation of two analyses of data from its Phase 3 pivotal clinical trials, TARGET 1 and 2, demonstrating a 14-day course of XIFAXAN 550 mg (rifaximin) taken three times daily achieved adequate relief of symptoms of non-constipation irritable bowel syndrome (non-C IBS) in a significantly greater proportion of patients compared with placebo. The data are being presented at the 2010 American College of Gastroenterology (ACG) Annual Scientific Meeting, being held this week in San Antonio, Texas.
“The Responsiveness and Validity of a Binary Weekly Recall Question and the Proposed FDA Composite Endpoint as Measures of Daily Symptom Severity in Non-Constipation Irritable Bowel Syndrome: Results of TARGET 1 and TARGET 2.”
Analysis of the daily assessment of symptom severity data substantiate the primary and key secondary endpoints, which were evaluated using a weekly assessment of adequate relief of global IBS symptoms and IBS-related bloating data - in TARGET 1 and 2 -- both independently and combined. Presentation of these findings was enhanced by a separate analysis of the data, presented during a poster session, which demonstrates alignment between the initial results (weekly adequate relief endpoints) and the results obtained when analyzed according to a composite endpoint proposed earlier this year by the U.S. Food and Drug Administration (FDA) to assist in the development of IBS treatments. The proposed composite endpoint is comprised of a daily assessment of abdominal pain and stool consistency.
"When daily symptom severity assessments were analyzed according to the proposed FDA composite endpoint, the results independently substantiated findings from the weekly adequate relief endpoints. A significantly higher percentage of XIFAXAN 550 mg-treated patients responded favorably for each endpoint, compared with placebo, within each study," said Mark Pimentel, M.D., Gastrointestinal Motility Program director at Cedars-Sinai Medical Center and principal investigator of the TARGET trials. "This analysis reinforces the potential of XIFAXAN 550 mg to address the needs of non-C IBS patients, many of whom suffer from symptoms daily."
In a separate analysis, the validity of binary "adequate relief," or global symptom improvement, as key efficacy endpoints historically used in IBS trials was compared to that of the proposed FDA composite endpoint. For each study and for the combined analysis, the weekly responder endpoints of adequate relief of global IBS symptoms and adequate relief of IBS-related bloating correlated consistently with the daily symptom severity scores assessed by the proposed FDA draft guidance using a composite endpoint of abdominal pain and stool consistency.2
"The complexity of irritable bowel syndrome creates a challenge in developing optimal endpoints and trial design for evaluating the efficacy of IBS treatments. It is exciting to report that in our analysis of TARGET 1 and 2 data, XIFAXAN 550 mg proved effective for a significantly greater proportion of non-constipated IBS sufferers than placebo, regardless of how the data were analyzed - both by the binary "adequate relief" weekly endpoints and by the proposed FDA composite endpoint of daily measures of symptom severity," said William Chey, M.D., professor of medicine in the Division of Gastroenterology and director of the Gastrointestinal Physiology Laboratory at the University of Michigan Health System. "There has also been discussion as to whether it is best to measure symptom response in IBS patients on a weekly or daily basis. Our analysis indicates clinical outcomes in terms of symptom response are very similar, regardless of whether assessments are conducted weekly or daily."
XIFAXAN 550 mg is Salix's minimally absorbed, gut selective, broad spectrum antibiotic currently under priority review by the FDA for the proposed indication of the treatment of non-C IBS and IBS-related bloating. The data presented at the ACG annual meeting were included in the package submitted to the FDA as part of the supplemental new drug application (sNDA) filing. The FDA is expected to rule on the sNDA filing by March 7, 2011.
"Salix is extremely pleased with the strength of the data generated from the TARGET 1 and 2 trials - including the additional confirmation of rifaximin's potential as analyzed by the proposed FDA composite endpoint," stated Bill Forbes, Pharm.D., Executive Vice President, Research and Development and Chief Development Officer, Salix. "We will continue to work closely with the FDA in anticipation of the completion of their review by March 7, 2011."