Salix Pharmaceuticals reported additional positive data from its Phase III studies of bowel drug candidate Xifaxan (rifaximin) showing that the drug provided acute and sustained relief of nonconstipation irritable bowel syndrome (non-C IBS) symptoms.
Compared to the placebo group, a significantly greater portion of patients who were given a 14-day course of Xifaxan 550 mg, three times daily, achieved adequate relief of IBS symptoms during the first four weeks, as well as over three months. "Two weeks of treatment gives three months worth of relief from IBS," Bill Forbes, executive vice president of research and development at Salix, said in summing up the results.
The data, presented at the Digestive Disease Week meeting in New Orleans, also showed that rifaximin provided adequate relief from bloating for two or more weeks, following the 14-day treatment period. In addition, the compound showed improvement of stool consistency and abdominal pain and discomfort.
The results are in line with earlier Xifaxan data from the two Phase III trials, which showed statistically significant reductions in IBS symptoms. (See BioWorld Today, Sept. 15, 2009.)
IBS is a condition characterized by abdominal pain, bloating and alternating bouts of diarrhea and constipation. Raleigh, N.C.-based Salix is working to submit a U.S. regulatory filing for rifaximin in non-C IBS by the end of June.
Rifaximin, an antibiotic, has been U.S.-approved to treat traveler's diarrhea since 2004 and was recently approved for overt hepatic encephalopathy, a brain disorder caused by chronic liver failure. (See BioWorld Today, Mar. 26, 2010.)
Rifaximin is designed to treat the cause of the disease - the overgrowth of organisms in the gut. The disease typically affects patients in their late 40s who are otherwise often healthy. It has been used in Italy for 24 years and is approved in 33 countries. Salix acquired rights to market rifaximin in North America from Alfa Wassermann SpA in Bologna, Italy. Alfa Wassermann markets rifaximin in Italy under the trade name Normix.
David Amsellem, senior research analyst at Piper Jaffray, stated in a research note that "Xifaxan is one of the most exciting product opportunities in specialty pharma and over time is likely to have well north of $1B in peak sales (combined sales in IBS and hepatic encephalopathy)."
Currently, Lotronex is approved for diarrhea-predominant IBS but due to safety reasons it is restricted to females with severe diarrhea. Salix's product is aimed at both males and females and could be used in mild-to-moderate cases of nonconstipation IBS, Forbes explained.
Some 10 percent to 15 percent of Americans have IBS, and includes altered bowel habits with abdominal pain and discomfort.
Forbes pointed out that a late-stage IBS drug being developed by Ironwood Pharmaceuticals Inc. is aimed at the smaller IBS population with constipation, while rifaximin is aimed at the larger population with nonconstipation IBS.
San Diego-based Tioga recently reached an agreement with the FDA on a special protocol assessment for its Phase III trials of asimadoline in diarrhea-predominant IBS. Asimadoline, a small-molecule kappa opioid agonist, originally was discovered by Merck KGaA, of Darmstadt, Germany.
Ironwood, of Cambridge, Mass., and New York-based Forest Laboratories Inc., have an investigational bowel drug, linaclotide, in development for chronic constipation and irritable bowel syndrome with constipation.
Salix shares (NASDAQ:SLXP) rose $1.51 to close at $42.57 Tuesday.
In other news from Digestive Disease Week:
• Alvine Pharmaceuticals Inc., of San Carlos, Calif., reported scientific data on lead compound ALV003 in a gastric simulation model. Alvine scientists developed a simple gastric digestion model to study the ability of ALV003 to degrade gluten in the context of a complex meal. The data from the simulation model were consistent with in vivo data from a Phase I study, with comparable degrees of gluten degradation observed. The current Phase IIa study is being conducted in well-controlled celiac disease patients receiving a daily gluten challenge for six weeks.
• Ironwood Pharmaceuticals Inc., Cambridge, Mass., and Forest Laboratories Inc., of New York, presented Phase III results assessing the efficacy and safety of the investigational drug linaclotide in patients with chronic constipation (CC). The data presented demonstrated that statistical significance vs. placebo was achieved for the primary endpoint of 12-week complete spontaneous bowel movement overall responder for each of the two doses studied in each trial. Treatment responses occurred within one week and were sustained over the 12-week treatment period. Linaclotide is a guanylate cyclase type C (GC-C) agonist in Phase III development for the treatment of irritable bowel syndrome with constipation and CC.
• Optimer Pharmaceuticals Inc., of San Diego, presented new data from its second fidaxomicin Phase III study in patients with clostridium difficile infection indicating that it significantly improved the recurrence rate and global cure rate in CDI patients requiring concomitant antibiotics, compared to vancomycin. New data from analyses of the study showed that subjects who were receiving concomitant antibiotics, treatment with fidaxomicin resulted in a significantly lower recurrence rate compared to treatment with vancomycin (17.6 percent vs. 29.5 percent, p = 0.027) and an improved global cure rate compared to treatment with vancomycin (67.5 percent vs. 53.4 percent, p = 0.020). The results confirmed findings from the first fidaxomicin Phase III study and suggested that, even when concomitant antibiotics are administered, fidaxomicin may be more effective than vancomycin in the treatment of CDI, the company said.
• Raptor Pharmaceutical Corp., of Novato, Calif., reported positive Phase IIa trial results from its pilot study of delayed-release cysteamine bitartrate in 11 adolescent patients with nonalcoholic steatohepatitis (NASH), a progressive form of liver disease believed to affect 5 percent to 11 percent of the U.S. population. Patients showed a marked decline in enzymes alanine transaminase levels during the treatment period with seven of 11 patients achieving a greater than 50 percent reduction and six of 11 reduced to within normal range.
• Sucampo Pharmaceuticals Inc., of Bethesda, Md., presented results of a Phase II trial of cobiprostone for the prevention of gastric ulcers and other gastrointestinal injuries in patients treated with non-teroidal anti-inflammatory drugs (NSAIDs). Data showed use of high-dose cobiprostone was associated with a 50 percent reduction in gastroduodenal ulcers when compared to placebo, and time to onset of all ulcer and erosion development was statistically significantly delayed in the cobiprostone groups across the 12-week treatment period.