Nearly half the patients suffering from primary
biliary cirrhosis who received the drug, obeticholic acid, achieved
the primary goals of the study, compared with 10 percent for those
who received a placebo, researchers said.
The composite main goal of the study was to achieve at least a 15
percent reduction in levels of alkaline phosphatase, a biomarker for
severity of the liver disease, serum alkaline phosphatase activity
of less than 1.67 times the upper limit of normal and bilirubin
within normal limits.
"Reduction in alkaline phosphatase is really the best prognostic
factor for survival," Dr. Frederik Nevens, the study's lead
investigator and chairman of the department of hepatology at the
University of Leuven, in Belgium, said in a telephone interview.
He called results "highly, highly significant."
Results of the 217-patient Phase III study, called Poise, were
presented at the annual meeting of the European Association for the
Study of the Liver (EASL) in London.
Primary biliary cirrhosis (PBC) is caused by autoimmune destruction
of the ducts that transport bile acids out of the liver, resulting
in toxic buildup of bile acids. The disease causes progressive liver
damage and often leads to need for a liver transplant or to death.
Obeticholic acid, a first-in-class drug, is being studied for those
who have an inadequate response to, or cannot tolerate, standard
treatment with an older generic medicine called ursodeoxycholic
Intercept said it plans to apply for approval later this year in the
United States and Europe for the medicine, which has received orphan
drug designation. In the United States orphan drug status, given to
drugs that treat rare diseases, comes with seven years of marketing
exclusivity if approved.
Obeticholic acid is also being tested to treat a much more common
fatty liver disease called nonalcoholic steatohepatitis. When a
Phase II study of the drug for that condition was stopped early
because the medicine was clearly effective, Intercept's stock price
nearly quadrupled to about $300 a share.
[to top of second column]
Nevens said he expects the convenient once-a-day pill to change
medical practice for primary biliary cirrhosis.
"Patients are dying and needing liver transplants. If this drug
comes on the market, I see no reason why we wouldn't use it," he
Patients in the year-long study had a moderate form of the disease,
and most on average had been taking the older medicine for about 10
They received either 5 milligrams or 10 mg of obeticholic acid or a
placebo. Those in the 5 mg group who had not had an adequate
response after six months were increased up to 10 mg for the final
Forty-six percent in the 5 mg group and those who switched to the
higher dose and 47 percent in the original 10 mg group achieved the
primary goal of the study, researchers said.
Liver tests on those who achieved the primary goal fell to levels
that correlate to improvement in the outcome of these patients, said
Nevens. In contrast, "there was a tendency of worsening of liver
disease in the placebo group," he said.
The most common side effect with the drug was severe itching, which
is also a symptom of the disease. The itching tends to be less
severe with lower doses and had been much worse in earlier trials
testing far higher doses, Nevens said.
Ten percent of those in the 10 mg group dropped out of the trial due
to itching, but only one patient who started on 5 mgs and later
switched to 10 mg discontinued treatment.
"Overall the drug is safe," Nevens said.
(Reporting by Bill Berkrot; editing by Leslie Adler)
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