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IMAGO: LUM001 fails to reduce bile acids, pruritus in pediatric patients with ALGS

VIENNA — Serum bile acids and pruritus remained unchanged in pediatric patients with allagile syndrome after treatment with LUM001, according to a late breaker presentation at the 2015 International Liver Congress.

“Alagille syndrome is a genetic disorder that often involves cholestasis,” Alastair Baker, MB ChB, FRCP, FRCPCH, pediatric liver consultant, King’s College Hospital, London, said in his presentation. “Accumulation of bile acids may lead to progressive liver disease and severe pruritus may be an indication for liver transplant.”

Baker and colleagues randomly assigned pediatric patients from three different pediatric centers in the United Kingdom with alagille syndrome (ALGS) to receive either LUM001 (Lumena Pharmaceuticals) or placebo for 28 days.

“The safety profile of this compound is well-established in over 1,400 adult humans,” Baker said. LUM001 dosing started at 14 µg/kg/day and increased weekly for 5 weeks to reach the target dose in each group, according to the research. All patients were screened for 4 weeks then randomized to different cohorts: cohort one included six patients who received 140 µg/kg; in cohort two, eight patients received 280 µ/kg and six patients received placebo.

The primary endpoint was change in fasting serum bile acid level from baseline to 13 weeks. Secondary endpoints were change in pruritus, assessed twice daily with a novel reported outcome measure (the ItchRO) using a hand-held electronic diary, according to Baker’s presentation.

Results indicated that the fasting serum bile acids in patients who received LUM001 compared with patients who received placebo were not different statistically from baseline or between the groups, according to Baker.

“We then performed a post-hoc analysis of the correlation between the percentage change in fasting serum bile acids and the vitro daily score,” Baker said.

A positive correlation between changes in bile acid and pruritus in patients treated with LUM001 was observed from the post-hoc analysis. Three patients responded well with respect to improvements in pruritus (between 32% and 82%) and had a 75% reduction in serum bile acids.

“The safety and tolerability was good, no severe adverse events were reported,” Baker said. “There were more diarrhea and abdominal pain in the LUM001 group compared to placebo, but not severe and the only patient who withdrew from the study was in the placebo group.”

Overall, the primary and secondary endpoints were not met in this study, according to Baker.

“This variable response is being assessed by additional complex analyses but overall the compound was tolerated,” Baker said. – by Melinda Stevens

For More Information:

Baker A. L04. Presented at: International Liver Congress; April 22-26, 2015; Vienna.

Disclosure: Baker reports no relevant financial disclosures. Please see the study for a full list of other authors’ relevant financial disclosures.