By Bill Berkrot
(Reuters) - A drug being developed by Intercept Pharmaceuticals Inc led to significant improvement in signs of a rare liver disease that primarily affects middle-aged women, likely reducing the risk of need for liver transplant and of death, according to results of a late-stage clinical trial presented on Saturday.
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 acid.
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.
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 said.
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 years.
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 six months.
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)