• New analysis demonstrates bilirubin normalization in PFIC patients treated with LIVMARLI (maralixibat); the only IBAT inhibitor reported to show this effect
• Sleep improvement observed in patients with PFIC correlated with maralixibat-driven pruritus reduction (selected as Best of EASL)
• Maralixibat demonstrates efficacy and maintenance of response in patients with ALGS who transition to adulthood

FOSTER CITY, Calif. / Jun 23, 2023 / Business Wire / Mirum Pharmaceuticals, Inc. (Nasdaq: MIRM) today announced data presented during the European Association for the Study of the Liver (EASL) Congress 2023, taking place in Vienna, Austria.

The congress presentations feature new analyses from the LIVMARLI® (maralixibat) 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 (PFIC), 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 (ALGS) was presented during EASL.

“We are delighted to see the significant impact LIVMARLI has on multiple measures of health for patients with PFIC, including improvements in key parameters such as sleep, long-term pruritus control and importantly, bilirubin, which is a marker of liver health and disease progression,” said Pam Vig, PhD, head of research and development at Mirum. “We are also very excited to report, for the first time, pruritus control with LIVMARLI in adult patients with Alagille syndrome, providing critical information as children transition to adult care. These data further demonstrate LIVMARLI’s ability to impact lives across these indications.”

Data from Mirum’s studies of LIVMARLI (maralixibat) 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 (total: -18.4 mmol/L vs. 15.9 mmol/L, p=0.047; direct: -12.9 vs. 13.5, p=0.048).
• 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 (94.4% with normalized total bilirubin on maralixibat, 19.0% without normalized total bilirubin on maralixibat, 3.3% without normalized total bilirubin on placebo).
• 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.

Read more in the detailed analysis.

LBP-35: Long-term maintenance of response and improved liver health with maralixibat in patients with progressive familial intrahepatic cholestasis (PFIC): Data from the MARCH-ON study
Late-breaker poster presentation

The analysis evaluated the long-term maintenance response to maralixibat in patients who were randomized to receive maralixibat (MRX-MRX) or placebo (PBO-MRX) in MARCH and continued treatment with maralixibat in MARCH-ON. Eighty-five patients from MARCH enrolled in MARCH-ON (47 MRX and 38 placebo). 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.

Read more in the detailed analysis.

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; ≥16 years transitioning to adult care and participants aged >16 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.

Read more in the detailed analysis.

WED-252: Maralixibat leads to significant reductions in pruritus and improvements in sleep for children with Progressive Familial Intrahepatic Cholestasis: Data from MARCH-PFIC
Selected to be included as part of ‘Best of EASL’ presentation

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 ≤1 (minimal to no itch) 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 (p=.0005).
• 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; p<0.000 for both analyses, suggesting that maralixibat may result in meaningful improvements in this aspect of quality of life.

Read more in the detailed analysis.

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.

Read more in the detailed analysis.

All presentations are available in the Publications and Presentations section on Mirum’s website.

About LIVMARLI® (maralixibat) oral solution

LIVMARLI® (maralixibat) oral solution is an orally administered, once-daily, ileal bile acid transporter (IBAT) inhibitor and the only approved medication by the U.S. Food and Drug Administration for the treatment of cholestatic pruritus in patients with Alagille syndrome (ALGS) 3 months of age and older. LIVMARLI is also the only approved IBAT inhibitor by the European Commission for the treatment of cholestatic pruritus in patients with ALGS two months and older. For more information for U.S. residents, please visit LIVMARLI.com.

Mirum has also submitted LIVMARLI for approval in the U.S. in cholestatic pruritus in PFIC patients three months of age and older, and in Europe, in PFIC for patients two months of age and older.

LIVMARLI is currently being evaluated in late-stage clinical studies in other rare cholestatic liver diseases including biliary atresia. LIVMARLI has received Breakthrough Therapy designation for ALGS and PFIC type 2 and orphan designation for ALGS, PFIC and biliary atresia. To learn more about ongoing clinical trials with LIVMARLI, please visit Mirum’s clinical trials section on the company’s website.

IMPORTANT SAFETY INFORMATION

LIVMARLI can cause side effects, including:

Changes in liver tests. Changes in certain liver tests are common in patients with Alagille syndrome and can worsen during treatment with LIVMARLI. These changes may be a sign of liver injury and can be serious. Your healthcare provider should do blood tests before starting and during treatment to check your liver function. Tell your healthcare provider right away if you get any signs or symptoms of liver problems, including nausea or vomiting, skin or the white part of the eye turns yellow, dark or brown urine, pain on the right side of the stomach (abdomen) or loss of appetite.

Stomach and intestinal (gastrointestinal) problems. LIVMARLI can cause stomach and intestinal problems, including diarrhea, stomach pain, and vomiting during treatment. Tell your healthcare provider right away if you have any of these symptoms more often or more severely than normal for you.

A condition called Fat Soluble Vitamin (FSV) Deficiency caused by low levels of certain vitamins (vitamin A, D, E, and K) stored in body fat. FSV deficiency is common in patients with Alagille syndrome but may worsen during treatment. Your healthcare provider should do blood tests before starting and during treatment.

Other common side effects reported during treatment were gastrointestinal bleeding and bone fractures.

US Prescribing Information
EU SmPC

About Mirum Pharmaceuticals, Inc.

Mirum Pharmaceuticals, Inc. is a biopharmaceutical company dedicated to transforming the treatment of rare liver diseases. Mirum’s approved medication is LIVMARLI^® (maralixibat) oral solution which is approved in the U.S. for the treatment of cholestatic pruritus in patients with Alagille syndrome three months of age and older, and in Europe for the same indication in patients two months of age and older.

Mirum has also submitted LIVMARLI for approval in the U.S. in cholestatic pruritus in PFIC patients three months of age and older and in Europe in PFIC for patients two months of age and older.

Mirum’s late-stage pipeline includes two investigational treatments for debilitating liver diseases affecting children and adults. LIVMARLI, an oral ileal bile acid transporter (IBAT) inhibitor, is currently being evaluated in clinical trials for pediatric liver diseases and includes the EMBARK Phase 2b clinical trial for patients with biliary atresia. In addition, Mirum has an expanded access program open across multiple countries for eligible patients with ALGS and PFIC.

Mirum’s second investigational treatment, volixibat, an oral IBAT inhibitor, is being evaluated in two potentially registrational studies including the VISTAS Phase 2b clinical trial for adults with primary sclerosing cholangitis and the VANTAGE Phase 2b clinical trial for adults with primary biliary cholangitis.

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Forward-Looking Statements

This press release includes forward-looking statements pertaining to the Company’s planned participation at a scientific conference, including data presentation title and synopsis, which may include discussion of the Company’s clinical and research data, including the discovery, development, therapeutic potential, and commercialization of our product candidates and technologies in PFIC and ALGS. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Words such as “will,” “goal,” “potential” and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon Mirum’s current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation, risks and uncertainties associated with Mirum’s business in general, the impact of the COVID-19 pandemic, and the other risks described in Mirum’s filings with the Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date on which they were made and are based on management’s assumptions and estimates as of such date. Mirum undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as required by law.