Intercept Pharmaceuticals Inc. (ICPT)’s much-anticipated experimental liver drug raised bad cholesterol and caused itching in some patients, spurring the need for more safety studies, researchers said. The shares fell after the company said it may need to consider a lower dose.
Patients who received Intercept’s drug, obeticholic acid, for nonalcoholic steatohepatitis, or NASH, had significantly more bad cholesterol than those on a placebo, according to a study of 283 patients published in the journal Lancet.
It also caused itching in about a quarter of patients, some so severely that it interfered with basic activities, the study found. Intercept will consider a lower dose of the drug for its final stage trial because of the itching, Chief Executive Officer Mark Pruzanski said on a conference call today.
The findings may affect the prospects for the company’s leading drug candidate, also known as OCA, against nonalcoholic steatohepatitis, a condition often found in people who are overweight or have diabetes. Marked by a slow, dangerous buildup of fat and inflammation that can damage the liver, NASH is symptomless early on and complicated to diagnose. More than 6 million people in the U.S. are believed to suffer from the disease, according to the National Institutes of Health.
Intercept shares fell 17 percent to $205.01 at 9:38 a.m. New York time. The stock had more than tripled this year.
Safety Questions
The therapy, which was being tested in a mid-stage study, was previously reported to reduce liver damage. Forty-five percent of patients saw improvement compared with 21 percent on placebo, according to the data released yesterday from the study known as Flint. Fibrosis, or liver scarring, improved in 35 percent of patients compared with 19 percent on a placebo.
The researchers said the benefit to the liver from Intercept’s therapy was similar to that from treatment with vitamin E and pioglitazone, a diabetes drug. They concluded that future studies “will need to address the consequences of these changes on cardiovascular outcomes” and the drug’s “long-term safety requires further clarification.”
Intercept’s market value has grown to $5.28 billion since the start of the year on anticipation for the medicine. Shares soared in January after the trial was stopped early and again in August when the New York-based company shared preliminary data showing OCA reversed liver damage.
Cholesterol Effect
Most people who have NASH die from heart disease, not liver disease, which makes cardiovascular effects of the drug more significant, said Nezam Afdhal, director of hepatology at Beth Israel Deaconess Medical Center.
“It’s a sizable LDL change,” Naveed Sattar, a professor of metabolic medicine at the University of Glasgow, said in a telephone interview, referring to bad cholesterol. “It’s enough of a concern that it could increase the patient’s heart disease risk.”
Another concern is that 33 of 141 patients on the drug reported itchiness, 21 who said it was “intense or widespread” and three who found the itchiness so bad it interfered with daily activity. Nine patients on placebo reported itchiness.
“If it’s very severe, it’s debilitating -- you can’t sleep and you can’t function,” said Vijay Shah, chairman of gastroenterology and hepatology at the Mayo Clinic in Rochester, Minnesota. Shah said the improvement in liver damage was “very encouraging,” but the elevated cholesterol and itching were “some reasons to pause and weigh the pros and cons.”
Rising Obesity
Non-alcoholic fatty liver disease, a precursor of NASH, is thought to affect 10 percent to 20 percent of the U.S. population. Two percent to 5 percent of Americans develop NASH, according to the NIH. The population is likely to increase given rising obesity.
The company plans to target the drug first against a rare disease called primary biliary cirrhosis, in which inflammation destroys bile ducts in the liver and leads to scarring. Its next steps with NASH would be to conduct third-phase trials. Three stages of clinical trials generally are required for new drugs to gain approval from U.S. regulators.
“This is a very interesting preliminary study but it will require more safety data,” Beth Israel’s Afdhal said. “It’s still phenomenally early.”