Rifaximin/Xifaxan - FDA Questions Impact Of Salix Drug On Hepatic Encephalopathy

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Rifaximin/Xifaxan - FDA Questions Impact Of Salix Drug On Hepatic Encephalopathy

WASHINGTON (Dow )--The Food and Drug Administration Friday questioned the impact of a proposed Salix Pharmaceuticals Ltd. (SLXP) drug that would treat a condition caused by the build-up of toxic substances in the body that impairs brain function known as hepatic encephalopathy.

The drug, rifaximin, is currently being sold at a different strength under the brand name Xifaxan, and is used to treat travelers & apos; diarrhea caused by E. coli.

Now the company is seeking approval to market the product for use in preventing additional flareups of hepatic encephalopathy, which is a worsening of brain function that occurs when the liver is no longer able to remove toxic substances in the blood, usually because of liver disease. Rifaximin is an antibiotic designed to treat disorders of the gut.

Rifaximin faces a review Tuesday by an outside panel of medical experts who serve on the FDA & apos;s gastrointestinal advisory committee. The FDA posted a review of the product to its Web site Friday.

The FDA panel is being asked to make recommendations about whether it thinks rifaximin should be approved to treat hepatic encephalopathy. The FDA isn & apos;t required to follows its panels & apos; advice, but it usually does.

The agency said the primary issue facing the agency was "whether the totality of the submitted data constitutes sufficient evidence that permits a conclusion that a clinically meaningful effect of Xifaxan in the reduction in recurrence of HE events...has been established."

However, the agency said the observed outcome seen in the main clinical study submitted by Salix was, "on its face persuasive."

The drug was studied in 299 patients with cirrhosis, or a type of liver damage, who had had two episodes of hepatic encephalopathy but were currently in remission.

The main study goal looked at the time to the first episode of hepatic encephalopathy during a six-month study. One hundred forty patients received 550 milligrams of rifaximin twice daily while 159 patients received a placebo, or fake drug.

At six months, so-called "breakthrough" episodes of hepatic encephalopathy were experienced by 22% of patients in the rifaximin group compared to 46% of patients in the placebo group. The difference translates into a 58% reduction in the risk of having another episode of hepatic encephalopathy among patients who received rifaximin.

But the FDA said the primary endpoint in the study was based on a so-called Conn score "which requires a subjective assessment and depends on clinician judgment." The FDA panel will be asked to discuss whether the endpoint was clinically meaningful.

Salix, in a document also posted to FDA & apos;s Web site summary, said rifaximin was effective and safe in the patient population studied.

"Rifaximin represents the first significant therapeutic advancement in the treatment of HE in over 30 years for patients in the U.S.," the company said.

http://online.wsj.com/article/BT-CO-20100219-706698.html?mod=WSJ_latestheadlines