- Maralixibat data highlights the relationship between the reduction of serum bile acids and pruritus intensity, improved growth, and other quality of life measures.
- Analysis of the natural variability of pruritus in children with Alagille syndrome demonstrates persistent severity.
- Volixibat data shows highly active dose levels selected for Phase 2 studies.
Mirum Pharmaceuticals, Inc. (NASDAQ:MIRM), a biopharmaceutical company focused on the development and commercialization of novel therapies for debilitating liver diseases, today announced new analyses from its maralixibat and volixibat clinical programs, as featured at the Annual Meeting of the American Association for the Study of Liver Diseases – The Liver Meeting Digital Experience™.
A summary of findings from each of the poster presentations is below. To view the data in full, please visit the AASLD section within the Events page on our corporate website.
"Data generated from six years of clinical evaluation of maralixibat in Alagille syndrome has offered key understandings in the severe burden of pruritus and related markers of cholestasis, helping to elucidate the potential benefit of maralixibat in this treatment setting," said Dr. Pam Vig, chief scientific officer at Mirum. "We are also excited to begin Phase 2 studies of volixibat in adult patients with cholestatic liver disease, which will evaluate dose levels shown to be effective in increasing bile acid excretion, suggesting the potential to reduce the burden of cholestasis in these settings."
Abstract #341: Pruritus intensity is associated with cholestasis biomarkers and quality of life measures after maralixibat treatment in children with Alagille syndrome
Alagille syndrome (ALGS)-associated pruritus is often extremely debilitating, resulting in bleeding, scarring, sleep disturbance, fatigue, and decreased quality of life, with significant impact on the patient and their family. This analysis, which utilized data from the maralixibat Phase 2b ICONIC study in pediatric patients with cholestatic pruritus associated with ALGS, evaluated how change in pruritus intensity is related to change in cholestasis markers and other clinical parameters. The study evaluated 31 patients, of which 27 were evaluated for this analysis over a 48-week period. Overall, the positive treatment effects of maralixibat in patients with ALGS demonstrate important correlations with multiple clinically relevant parameters. Pruritus, as measured by the fully validated Itch Reported Outcome Observer (ItchRO[Obs]) tool, was correlated with several parameters including the Clinician Scratch Scale, serum bile acids (sBA) and sBA subspecies, autotaxin, growth and quality of life measures, including fatigue.
Abstract #1792: Natural variability of pruritus in Alagille syndrome; an analysis from the ICONIC study utilizing the Itch Reported Outcome Observer (ItchRO[Obs]) tool
Pruritus is known to be one of the most burdensome symptoms associated with ALGS; however, the variability of its severity and frequency has not been fully established. Assessments rely on observer- or patient-reported outcomes measures. The ItchRO(Obs) and ItchRO(Pt) tools were used to assess the natural variability of pruritus in children with ALGS who were enrolled in the Phase 2b ICONIC, placebo-controlled, randomized study. The scores were assessed during the 28-day screening period of ICONIC, when no drug was administered. The results showed that both the morning and evening assessment of pruritus was persistent over time with minimal fluctuations in severity and frequency.
Abstract #1221: A Phase 1 dose-ranging study assessing fecal bile acid excretion by volixibat, an apical sodium-dependent bile acid transporter inhibitor, and coadministration with loperamide
The primary goal of this Phase 1 clinical study was to investigate the safety and efficacy of a range of dose levels and dose regimens of volixibat, to help guide dose selection for clinical trials in patients with cholestatic disease, in particular the planned Phase 2 programs in adult patients with primary sclerosing cholangitis and intrahepatic cholestasis of pregnancy. The study evaluated the effects of volixibat alone and in combination with loperamide, seeking to understand whether the addition of loperamide would reduce the mild gastrointestinal side effects that are often observed with ASBT inhibitors.
The analysis found that volixibat was well-tolerated at all dose levels and regimens evaluated. As expected for the mechanisms of action of volixibat, fecal bile acid excretion was increased across all treatment groups. Overall, twice-daily dosing was associated with greater increases in bile acid excretion compared to once-daily dosing. Use of volixibat in adult healthy volunteers was associated with meaningful increases in fecal bile acid excretion and serum 7αC4, which are markers of bile acid synthesis. In addition, standard dosing of loperamide helped to reduce the mild and transient gastrointestinal disturbance during the initial dosing of volixibat, without a drug-drug interaction. The effects on bile acid trafficking and synthesis support the further study of volixibat in patients with cholestatic liver disease.