Salix Pharmaceuticals, Ltd. reported that the Gastrointestinal Drugs Advisory Committee of the FDA has recommended by a vote of 14 to 4 in favour of the approval of Xifaxan (rifaximin) tablets, 550 mg for the maintenance of remission of hepatic encephalopathy (HE).
"We are very pleased with the advisory committee's support for the approval of Xifaxan 550 mg tablets. If approved, Xifaxan 550 mg will be the first new option for the management of hepatic encephalopathy in over 30 years," stated Bill Forbes, Pharm.D., senior vice president research and development and chief development officer, Salix. "We believe the availability of Xifaxan 550 mg has the potential to change the treatment paradigm for HE. Today's independent recommendation from the outside experts comprising the advisory committee reinforces the company's confidence in the potential for Xifaxan 550 mg to provide a solution for patients suffering from this serious condition."
The committee reviewed data from the company's 299-subject, double-blind, placebo-controlled, multinational, phase 3 study. This study demonstrated a statistically significant and clinically meaningful reduction in the risk of recurrent overt HE. The primary endpoint - the risk of experiencing a breakthrough overt HE episode - was reduced by 58 per cent in Xifaxan 550 mg-treated subjects compared with placebo (p<0.0001). The key secondary endpoint - risk of experiencing HE-related hospitalization - was reduced by 50 per cent in Xifaxan 550 mg-treated subjects compared with placebo (p=0.0129). The committee also reviewed supporting evidence from the company's long-term, open-label, Phase 3 study, as well as evidence derived from clinical studies in acute HE, three-month and six-month studies from the published literature and meta-analyses.
The FDA convenes the Gastrointestinal Drugs Advisory Committee to obtain independent expert advice on a broad scope of issues relating to gastrointestinal drug products. The committee provides non-binding recommendations which will be considered by the FDA in its final review; however, the final decision on approval of the drug is made by the FDA.
The FDA has issued an action date of March 24, 2010 under the Prescription Drug User Fee Act for the Xifaxan 550 mg HE NDA. Xifaxan has been granted Orphan Drug designation by the FDA for use in hepatic encephalopathy. Salix believes this designation will provide seven years of marketing exclusivity in the United States if Xifaxan approval from the FDA for HE.
Hepatic encephalopathy occurs frequently in patients with cirrhosis as a result of their end-stage liver disease. Typically the cirrhosis is caused by a number of factors, such as alcohol and/or drug abuse, chronic viral hepatitis and autoimmune disease. There are more than 600,000 cases of cirrhosis in the United States and it is a leading cause of death in the United States. The number of cases of liver disease in the United States and around the world is rapidly increasing, with the estimated prevalence of chronic liver disease in the United States believed to be between 6 and 7 million cases. There are reported to be approximately 200,000 patients in the United States with overt HE.
Rifaximin is a gut-selective antibiotic with negligible systemic absorption (<0.4%) and broad-spectrum activity in vitro against both gram-positive and gram-negative pathogens. Rifaximin has a similar tolerability profile to that of placebo.
Rifaximin tablets 200 mg, which Salix markets in the United States under the trade name Xifaxan (rifaximin) tablets 200 mg, currently is approved for the treatment of patients, 12 years of age or older, with travelers' diarrhea (TD) caused by non-invasive strains of Escherichia coli. Xifaxan (rifaximin) is a gut-selective antibiotic with negligible systemic absorption (<0.4%) and broad-spectrum activity in vitro against both gram-positive and gram-negative pathogens. Rifaximin has a similar tolerability profile to that of placebo and has activity against the most common TD pathogens. Xifaxan should not be used in patients with diarrhea complicated by fever or blood in the stool or diarrhoea due to pathogens other than Escherichia coli. Xifaxan should be discontinued if diarrhoea symptoms get worse or persist more than 24-48 hours and alternative antibiotic therapy should be considered. In clinical trials, Xifaxan was generally well tolerated. The most common side effects (vs. placebo) were flatulence 11.3% (versus 19.7%), headache 9.7% (versus 9.2%), abdominal pain 7.2% (versus 10.1 %) and rectal tenesmus 7.2% (versus 8.8%).
Rifaximin 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 S.p.A. in Bologna, Italy. Alfa Wassermann markets rifaximin in Italy under the trade name Normix.
Salix Pharmaceuticals, Ltd., headquartered in Raleigh, NC, develops and markets prescription pharmaceutical products for the treatment of gastrointestinal diseases.