Mirum Pharmaceuticals presents data on LIVMARLI at EASL Congress

Mirum Pharmaceuticals announced data presented during the European Association for the Study of the Liver Congress 2023, taking place in Vienna, Austria. The congress presentations feature new analyses from the LIVMARLI oral solution MARCH-PFIC study as well as the long-term extension study, MARCH-ON. MARCH-PFIC is the largest Phase 3 trial in progressive familial intrahepatic cholestasis, evaluating all types, including genetic types that had not previously been studied. The data underscore long-term maintenance of effect, markers of improved liver health, impact on sleep improvement and long-term safety data. Additionally, data showing LIVMARLI’s benefit in adult patients with Alagille syndrome was presented during EASL. Data from Mirum’s studies of LIVMARLI include oral and poster presentations: Abstract OS-072: Maralixibat leads to significant reductions in bilirubin for patients with Progressive Familial Intrahepatic Cholestasis: Data from MARCH-PFIC: The goal of the analysis was to characterize the impact of maralixibat on bilirubin in patients with PFIC as part of the MARCH Phase 3 study, specifically evaluating the mean change in baseline in total and direct bilirubin. Clinical evidence suggests that elevated serum bilirubin levels may indicate poorer outcomes in patients with PFIC. The data demonstrated: Maralixibat resulted in statistically significant improvements in total and direct bilirubin in the All-PFIC cohort versus placebo. Of the patients with abnormal total bilirubin values at baseline, 40% of maralixibat-treated patients achieved normalization, versus none in the placebo group. Reductions in bilirubin corresponded with reductions in serum bile acids. Data suggest that maralixibat may yield clinical improvements in liver health in patients with PFIC. Maralixibat is the only IBAT inhibitor to demonstrate significant decreases in total and direct bilirubin compared with placebo in patients with PFIC. LBP-35: Long-term maintenance of response and improved liver health with maralixibat in patients with progressive familial intrahepatic cholestasis: Data from the MARCH-ON study: The analysis evaluated the long-term maintenance response to maralixibat in patients who were randomized to receive maralixibat or placebo in MARCH and continued treatment with maralixibat in MARCH-ON. Eighty-five patients from MARCH enrolled in MARCH-ON. Baseline was defined as the start of maralixibat treatment for each group. The results showed: Significant improvements observed in the first 26 weeks of the MARCH study were sustained from Baseline to Week 52 in MARCH-ON for pruritus severity, sBA levels, total bilirubin, height -score and weight Z-score in the MRX-MRX group. Newly gained statistically significant reductions in pruritus severity and sBA levels were observed in the key efficacy endpoints from Baseline to Week 26 in the MRX-PBO group, in line with observations from the initial MARCH maralixibat group. No new safety signals were identified. The most frequent treatment emergent adverse events were gastrointestinal-related, in line with the mechanism of action of IBAT inhibition, mostly mild and transient. Patients who previously received maralixibat in MARCH were less likely to have events in MARCH-ON compared to MARCH. The data suggest overall improved liver health following maralixibat treatment in patients with PFIC, which are maintained over time. WED-257: Impact of maralixibat on cholestatic pruritus in adults aged 16 years and older with Alagille syndrome: Previous data in ALGS has been largely focused on pediatric populations; however, 24-40.3% of patients with ALGS reach 18 years of age with their native liver and may require treatment for cholestasis and pruritus. This analysis reported, for the first time, the efficacy and safety of maralixibat in adult patients with ALGS; greater than or equal to16 years transitioning to adult care and participants aged greater than16 years who initiated treatment in the ALGS clinical program. Results demonstrated that: Patients receiving maralixibat during childhood had significant improvements in pruritus that were maintained into adulthood. Maralixibat was generally well-tolerated and demonstrated a safety and tolerability profile consistent with previously reported data. The observations in this analysis support the potential for maralixibat to have a positive impact on the treatment for adults with ALGS who survive with their native liver into adulthood. WED-252: Maralixibat leads to significant reductions in pruritus and improvements in sleep for children with Progressive Familial Intrahepatic Cholestasis: Data from MARCH-PFIC: The analysis evaluated data from the Phase 3 MARCH-PFIC study and assessed pruritus response, as well as the relationship between a reduction in pruritus and an improvement in sleep. The proportion of patients with an itch score of less than or equal to1 during treatment, the measurement of pruritus at different times throughout the day, the physician’s assessment of pruritus, and the overall impact of pruritus on sleep were assessed. The data demonstrated that: Maralixibat was associated with complete or near-complete resolution of pruritus in the majority of patients with PFIC; the median proportion of days with pruritus scores of 0-1 was 95% for maralixibat and only 9% for placebo. The effect of maralixibat on pruritus was independent of when or how it was measured, or who made the assessments. Absolute values of pruritus as well as changes in pruritus were strongly correlated with improvements in sleep; spearman r=0.93; pless than0.000 for both analyses, suggesting that maralixibat may result in meaningful improvements in this aspect of quality of life. WED-282: Analysis of safety in maralixibat-treated participants with Progressive Familial Intrahepatic Cholestasis: Data from MARCH-PFIC: The poster provided a detailed safety analysis from the MARCH-PFIC clinical trial, the largest and most genetically inclusive study of PFIC to date and included participants with variants not known. The analysis showed that maralixibat was overall well-tolerated with no new safety signals observed. The most frequent treatment-emergent adverse events were gastrointestinal and were generally mild with only 5.5 days duration. Fat soluble vitamin deficiency and increased bilirubin occurred more frequently in the placebo group compared with maralixibat. No changes in liver enzymes were observed over the duration of the study and individual elevations were mild and transient; there were no discontinuations. All serious adverse events resolved without any dose reductions. Overall, dosing with maralixibat was shown to be well-tolerated with an acceptable safety profile for chronic dosing.