麻豆传媒

WASHINGTON -- A drug approved for one form of cholangitis is showing promise in another, a researcher said here.

In a placebo-controlled phase II trial, obeticholic acid (Ocaliva) led to significant reductions in alkaline phosphatase, a marker of liver injury, in patients with primary sclerosing cholangitis (PSC), according to Kris Kowdley, MD, of Swedish Medical Center in Seattle.

At the same time, it was safe and well tolerated although it was associated with dose-dependent increases in pruritus, Kowdley told a late-breaker session at the Liver Meeting, the annual conference of the

Obeticholic acid, also known as OCA, was approved last year to treat patients with primary biliary cholangitis (PBC) with an inadequate response to, or intolerant of, the standard of care medication, ursodeoxycholic acid (UDCA).

There are currently no approved therapies for PSC, a rare cholestatic liver disease, which can lead to cirrhosis, cholangiocarcinoma, and early death. OCA is a selective farnesoid X receptor agonist that lowers bile acid synthesis and uptake, and raises bile secretion.

The study showed "certainly encouraging reductions in alkaline phosphatase," commented Raymond Chung, MD, of Massachusetts General Hospital in Boston, who was not part of the study but who co-moderated the session at which it was presented.

"It's certainly a step forward and potentially a basis for additional studies," he told 麻豆传媒. But he cautioned that researchers will need to be very careful in cholestatic diseases given that there have been some recent for treatment with the drug in PBC, especially in patients with hepatic impairment.

"We need to make sure there is nice therapeutic safety window," he said.

He added that the use of alkaline phosphatase as a prognostic marker is not as well established in PSC as it is in PBC.

In the so-called , Kowdley and colleagues randomly assigned 77 patients with PSC to get a placebo or one of two doses of OCA -- 1.5 or 5.0 mg for 12 weeks. At the end of 12 weeks, patients in each active arm could have their dose doubled. The investigators plan a two-year safety extension study.

The primary endpoints of the 24-week double-blind part of the study were changes in alkaline phosphatase and safety, Kowdley said.

Patients all had baseline alkaline phosphatase levels of at least double the upper limit of normal. Interestingly, although there are no approved therapies for PSC, just under half of the patients in the study were taking UDCA, he noted.

At the end of 12 weeks, Kowdley said, the average level of alkaline phosphatase had dropped 9% among placebo patients, 11% among those on 1.5 mg of OCA, and 27% among those on the 5.0-mg dose.

Most patients in the active arms opted to increase their OCA dose, he said, and at the end of the subsequent 12 weeks, average changes in alkaline phosphatase were +1% for placebo and -22% for both active arms.

The use of UDCA did not affect changes in the enzyme, he reported.

The most common adverse event was pruritus, affecting 46% of placebo patients, 60% of those on the lower doses, and 67% of those getting the higher doses, Kowdley said. The symptom was manageable and only four patients stopped therapy because of it, all in the active arms.

On the other hand, the severity of the pruritus was increased with increasing doses of the drug, he reported.

Serious adverse events were infrequent and similar across all three arms, he said.

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