Data Shows Rifaximin Provided Significant Protective Effect in
Preventing HE Breakthrough and HE-Related Hospitalization
Salix Pharmaceuticals, Ltd. (NASDAQ:SLXP) today announced the
presentation of new data from its Phase III pivotal clinical trial
evaluating the efficacy, safety and tolerability of rifaximin - a
non-absorbed (<0.4%), gut selective antibiotic - in adult patients with
hepatic encephalopathy (HE). These data, presented during two oral
sessions at the annual meeting of Digestive Disease Week (DDW) being
held this week in Chicago (May 30-June 4, 2009), demonstrated that
rifaximin significantly reduced the risk of HE-related hospitalizations
in patients with previous episodes of HE and showed a highly significant
reduction in the risk of breakthrough HE during the six month study.
The new data come from two additional analyses of the pivotal Phase III,
multinational, randomized, double-blind, placebo-controlled study of 299
patients with a history of HE. The data showed that patients who
received rifaximin (1100 mg / day, dosed at 550 mg twice daily) for six
months experienced a highly statistically significant reduction in the
risk of breakthrough HE compared to those who received placebo (58% risk
reduction, p<0.0001) in the intent to treat (ITT) population. One
analysis presented today showed that rifaximin significantly reduced the
risk of HE-related hospitalizations compared to placebo (50% risk
reduction, p=0.01) during the six month treatment period. The other data
analysis presented showed that rifaximin treatment after adjusting for
significant prognostic factors (such as geographic location, age, sex,
race, model for end-stage liver disease [MELD], and Conn score – that
can contribute to breakthrough HE) resulted in a 60% risk reduction
demonstrating a highly significant protective effect (p<0.0001) in
preventing HE breakthrough.
"The findings in this study that rifaximin use decreases the
hospitalization rate by 50 percent for those with frequent episodes of
HE within only six months is quite impressive,” said Samuel H. Sigal,
MD, Assistant Professor of Medicine, Weill Cornell Medical College, New
York. "This represents a major advance for a condition that until now
had limited options.”
The 299 patients were randomized to either rifaximin (n=140) 550 mg /
bid, or placebo (n=159). Patients with cirrhosis who had ≥2 episodes of
HE (defined as Conn score ≥2) within six months prior to screening and
were currently in remission (defined as a Conn score = 0 or 1) were
enrolled in the study. The primary endpoint was time to first
breakthrough HE episode (increase of Conn score to ≥2; or a Conn score
and asterixis grade increase of 1 each, if baseline Conn score = 0).
O144. The Effect of Prognostic Factors on the Maintenance of
Remission in Hepatic Encephalopathy Patients Treated with Rifaximin
(Oral Presentation, Sunday, May 31, 2009, 10:30 - 10:45 AM CT, #
144)
In an oral presentation, Dr. Sigal and colleagues presented the results
of an additional analysis of the Phase III study that demonstrated
rifaximin significantly reduced the risk of breakthrough HE by 60%
versus placebo (HR, 0.403; 95% confidence interval (CI), 0.264-0.617;
p<0.0001) during the six month treatment period. The most influential
prognostic factors for maintenance of remission in this covariate
analysis were age (p=0.03) and MELD score (p=0.0003).
O66. Rifaximin Reduces Hospitalizations in Patients with Previous
Episodes of Hepatic Encephalopathy: Results from a Phase 3
Placebo-Controlled Trial
(Oral Presentation: Sunday, May 31, 2009, 9:30 - 9:45 AM CT, #66)
In another oral presentation earlier today, Dr. Neff and colleagues
presented the results of an additional analysis that showed rifaximin
provided significant reduction in the risk of HE-related
hospitalizations by 50% compared to placebo (hazard ratio=0.500; 95% CI,
0.287-0.873; p=0.01). The data also indicated on average that for every
nine patients treated with rifaximin one fewer patient was hospitalized
due to HE.
“This new data solidly supports the clinical efficacy of rifaximin in
reducing the risk of HE-related hospitalization,” said Guy Neff, MD,
MBA, Medical Director of Transplant and Associate Professor of Clinical
Medicine, Hepatology and Transplant at the University of Cincinnati,
College of Medicine. “As demonstrated in previously published
pharmacoeconomic data, reducing recurrent HE events may reduce the need
for HE-related hospitalization, thereby potentially decreasing the costs
of care.”
Other Rifaximin Presentations at DDW
In addition to the presentations by Dr. Sigal and Dr.
