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VIENNA -- Treatment with oral elafibranor was associated with significant decreases in alkaline phosphatase (ALP) and other biochemical markers of primary biliary cholangitis PBC compared with placebo, researchers reported here.

In the phase II study, two different doses of elafibranor significantly decreased mean ALP compared with placebo (P<0.001), with reductions of 48% with the 80 mg/day dose, and 41% with the 120 mg/day dose. There was a increase of 3% in mean ALP with placebo, according to Velimir Luketic, MD, of Virginia Commonwealth University in Richmond, and colleagues.

At week 12, 67% and 79% of participants who received elafibranor of 80 mg/day and 120 mg/day, respectively, had an ALP <1.67 x the upper limit of normal (ULN), a reduction in ALP >15%, and a total bilirubin within normal limits compared with 6.7% of participants who received placebo, they said in a late-breaking presentation at the European Association for the Study of the Liver annual meeting.

Significant improvements in lipid and inflammatory markers and a trend in decreased pruritus were also observed, he reported.

"Twelve weeks of elafibranor treatment was well tolerated, and produced marked improvements [in] alkaline phosphatase and other biochemical markers of primary biliary cholangitis in this phase II study," Luketic said in a . "These results suggest the treatment has substantial anticholestatic efficacy that we hope will translate into long-term benefits for patients."

Elafibranor is an investigational oral treatment that has anti-inflammatory properties and decreases the synthesis and toxicity of bile acids.

The phase II study involved 45 individuals (mean age 59) with PBC without cirrhosis who had not responded adequately to ursodeoxycholic acid (UDCA) treatment, defined as an ALP >1.67 x ULN, and were randomized to receive 12 weeks of add-on oral elafibranor at a dose of 80 mg/day or 120 mg/day or to placebo.

Patients were eligible if they had been on UDCA for at least a year, but had not derived what physicians considered an adequate response to the therapy.

Following a screening period, the patients were assigned to either dose of elafibranor or placebo and underwent clinical and laboratory exams at the start of the trial, and at week 2, week 4, week 8, and week 12. Follow-up was done 2-4 weeks later at the end of the study.

The primary endpoint of the study was the percentage change from baseline in ALP at week 12 relative to placebo.

Luketic also reported that treatment with elafibranor was associated with reductions in gamma-glutamyl transferase; showed improvements in lipid markers including total cholesterol, LDL and triglycerides; reduction of anti-inflammatory markers; and a decrease in C4, an intermediate of bile acid synthesis.

Luketic noted that because patients had similar responses to both doses of elafibranor, it was likely that the phase III study would use the 80-mg dose in hopes of preventing drug-related adverse events.

EASL press conference moderator Francesco Negro, MD, of the University of Geneva, told 木瓜直播, "The effects seen with elafibranor occur very quickly, in about half the time as with other drugs being tested. This is a very promising drug, and I think I would favor it over fibrates. These are very interesting drugs."

"An optimal therapy for PBC has yet to be discovered; however the current study is of major significance, since it opens the path for a new molecule to be used in the clinical setting' commented Marco Marzioni, MD, of the Università Politecnica delle Marche in Ancona, Italy, in a press release.

"Although this is still a phase II study, the results are solid and very promising; a sign of a better future for our patients," he stated.

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