Livmarli helps clear fatty skin growths in Alagille kids, study finds
Trial data also show treatment reduces cholesterol
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Treatment with Livmarli (maralixibat) can reduce cholesterol levels and help clear fatty skin growths called xanthomas in children with Alagille syndrome, according to a new analysis of data from two clinical trials.
“Although [itch] relief remains [Livmarli’s] primary approved indication, our findings suggest a broader therapeutic potential, specifically in improving disfiguring xanthomas and associated [high cholesterol levels],” the researchers wrote.
The study, “Maralixibat Improves Xanthomas and Hypercholesterolemia in Children with Alagille Syndrome: A Post Hoc Integrated Analysis From Two Clinical Trials,” was published in The Journal of Pediatrics. The work was funded by Livmarli’s developer Mirum Pharmaceuticals, and several co-authors are employees of the company.
Alagille is a rare genetic disorder that often leads to cholestasis (slow or stalled flow of the digestive substance bile from the liver to the intestines). This can cause bile acids (the main component of bile) to accumulate to toxic levels in the liver and to leak out into the bloodstream, resulting in itching and other Alagille symptoms.
Cholesterol is a fatty substance that’s excreted from the liver into bile. In people with Alagille syndrome, impaired bile flow can result in cholesterol accumulating to abnormally high levels in the blood and tissues. This can lead to xanthomas, which are cholesterol-rich deposits in the skin that can cause pain and limit mobility.
Livmarli benefits
Livmarli is approved to help ease itching in people with Alagille. The oral therapy works by suppressing bile recycling from the intestines back to the liver, thereby promoting bile excretion in stools and reducing its buildup in the liver and blood.
Clinical trials have demonstrated that Livmarli can sustainably reduce blood bile acid levels and cholestasis-related itching in Alagille patients. However, there isn’t much published data on how the therapy affects cholesterol levels and xanthomas in children with the disease.
To fill this gap, the team of scientists conducted a post hoc analysis of clinical trial data, or an analysis designed and carried out once the study is over and all the data are available.
They integrated data from two placebo-controlled Phase 2 clinical trials that tested Livmarli in kids with Alagille, ICONIC (NCT02160782) and ITCH (NCT02057692), as well as ITCH’s long-term extension study, IMAGINE-II (NCT02117713).
Sixty-three Livmarli-treated children who had completed the Clinician Xanthoma Scale (CXS) at the start of the trial were included in the final analysis. CXS rates the severity of xanthomas on a scale from zero (no lesions) to four (severe lesions that substantially hinder daily activities).
At the start of the clinical trials, 43% of the children had a CXS score of at least 1, reflecting the presence of xanthomas. CXS scores were significantly higher (worse) in younger children, “suggesting that more severe and earlier-onset disease may predispose to xanthoma formation,” the researchers wrote.
Higher CXS scores were also significantly associated with higher blood levels of cholesterol, bile acids, and liver damage markers, as well as poorer scores on quality-of-life measures.
“These findings emphasize the relationship between xanthomas and [body-wide] disease severity,” the scientists wrote.
Mean CXS scores were significantly reduced after 96 weeks (about two years) of treatment, indicating a reduction in xanthoma severity. Of the 14 children with xanthomas at enrollment who had available data at 96 weeks, nine (64%) experienced a decrease in CXS score.
“The proportion of participants with no visible xanthomas (CXS 0) increased from 60% at [the trial’s start] to … 86% at week 96,” the team wrote.
Livmarli was also associated with decreases in blood cholesterol and bile acid levels. And patients who experienced reductions in xanthoma severity with the therapy were generally more likely than those who didn’t to see reductions in itching and improvements in quality of life.
Overall, the data suggest that Livmarli may help eliminate xanthomas in kids with Alagille, the researchers concluded.
They noted, however, that because the analysis was limited to a small number of patients and the CXS is a somewhat subjective assessment, the findings should be interpreted cautiously.
“Future studies should investigate predictive markers of xanthoma development and evaluate whether earlier or more targeted treatment can prevent or reverse this burdensome complication of [Alagille syndrome],” the team wrote.
