Chronic constipation is a feature of children with cystic fibrosis (CF). This is postulated to be a result of inhibition of secretory activity of the gastrointestinal luminal cells due to ineffective chloride channel function. Typical laxatives that work as osmotic agents fail to produce adequate relief in this population.
Maralixibat is a non-systemic bile acid transport inhibitor (IBATi) that acts by interrupting bile acid reabsorption in the ileum thus interrupting the normal enterohepatic circulation. This interruption results in a larger volume of bile acids reaching the colon and being excreted in stool. Bile acids are known to decrease bowel transit time, increase mucosal permeability and secretions, as well as alter gut microbiota resulting in diarrhea.
The overarching hypothesis of the study is that Maralixibat will improve stool consistency in children (Age <18 years) with cystic fibrosis and constipation (Bristol Stool Scale <4). Specifically, we aim to test the hypothesis that IBATi improves the consistency of stool to Bristol scale >4 in children with CF and constipation.
We will recruit a total of 20 patients with CF and constipation (defined as Bristol Stool Scale <4 for 1 week prior to enrollment while on a stable laxative regimen for at least 4 weeks.) Design is a 'Within-Subjects' study by which each enrolled patient will take Maralixibat for 2 weeks total in addition to their stable laxative regimen during the study. Stool consistency & ease of defecation will be recorded before and during the study period by families of enrolled patients via materials provided by the investigators. Stool consistency and ease of defecation will be compared before and after initiation of Maralixibat.
The primary endpoint: Improvement in stool consistency to Bristol scale >4 in children with CF and constipation. The secondary endpoint: Improvement in ease of defecation in children with CF and constipation. This will be measured via survey using a standardized scale (Bristol Stool Scale) and questionnaires developed by the research team. Analysis will involve comparison of pre-intervention to post-intervention stool consistency & survey

Start Date01 Jul 2024

Sponsor / Collaborator

Children's Hospital Los Angeles

NCT06193928 / RecruitingNot Applicable

Long-Term Safety and Clinical Outcomes of Livmarli in Patients With Alagille Syndrome (LEAP)

The goal of this observational study is to evaluate the long-term safety and clinical outcomes of Livmarli prescribed to patients with Alagille Syndrome (ALGS).

Start Date21 Sep 2023

Sponsor / Collaborator

Mirum Pharmaceuticals, Inc.

NCT05543174 / Active, not recruitingPhase 3

An Open-Label, Phase 3 Study to Evaluate the Efficacy and Safety of TAK-625 in the Treatment of Subjects With Alagille Syndrome

The main aim of the study is to check if TAK-625 improves symptoms of Alagille Syndrome (ALGS), side effect from the study treatment or TAK-625, and how much TAK-625 stays in their blood over time. This will help the study sponsor (Takeda) to work out the best dose to give people in the future.
The participants will be treated with TAK-625 for up to the end of study (about 34 months).
Participants will visit their study clinic 9 times from the start of study. After 9 times visits, participants will visit their study clinic every 12 weeks up to the end of study.

Start Date16 Jan 2023

Sponsor / Collaborator

Takeda Pharmaceutical Co., Ltd.

100 Clinical Results associated with Maralixibat Chloride

100 Translational Medicine associated with Maralixibat Chloride

100 Patents (Medical) associated with Maralixibat Chloride

Literatures (Medical) associated with Maralixibat Chloride

01 Jan 2024·The Lancet. Child & adolescent health

Paediatric research sets new standards for therapy in paediatric and adult cholestasis

Review

Author: Maher, Eamonn R ; Kelly, Deirdre ; Jeyaraj, Rebecca

Children with Alagille syndrome and progressive familial intrahepatic cholestasis (PFIC) experience debilitating pruritus, for which there have been few effective treatment options. In the past 2 years, the ileal bile acid transporter (IBAT) inhibitors maralixibat and odevixibat have been approved for the management of cholestatic pruritus in these individuals, representing an important step forward in improving their quality of life. Emerging data suggest these drugs might also improve event-free survival, therefore potentially altering the typical disease course currently seen in these disorders. This Review will discuss how genetic advances have clarified the molecular basis of cholestatic disorders, facilitating the development of new therapeutic options that have only been evaluated in children. We focus specifically on the newly licensed IBAT inhibitors for patients with Alagille syndrome and PFIC and explore the next steps for these drugs in relation to other paediatric and adult cholestatic disorders, recognising that they have the potential to benefit a wider group of patients with gastrointestinal and liver disease.

01 Dec 2023·Hepatology (Baltimore, Md.)

Predictors of 6-year event-free survival in Alagille syndrome patients treated with maralixibat, an ileal bile acid transporter inhibitor

Article

Author: Gonzales, Emmanuel M ; Baker, Alastair ; Mogul, Douglas B ; Jacquemin, Emmanuel ; Garner, Will ; Hansen, Bettina E ; Vig, Pamela ; Kamath, Binita M ; Sokol, Ronald J ; Thompson, Richard J

Background and Aims::

Refractory pruritus and other complications of cholestasis are indications for liver transplantation (LT) in patients with Alagille syndrome (ALGS). We evaluated predictors of event-free survival and transplant-free survival in patients with ALGS treated with maralixibat (MRX), an ileal bile acid transporter inhibitor.

Approach and Results::

We assessed patients with ALGS from 3 clinical trials of MRX with up to 6 years of follow-up. Event-free survival was defined as the absence of LT, surgical biliary diversion, hepatic decompensation, or death; transplant-free survival was the absence of LT or death. Forty-three potential predictors were evaluated, including age, pruritus (ItchRO[Obs] 0–4 scale), biochemistries, platelets, and serum bile acids. Harrell’s concordance statistic assessed goodness-of-fit, and then, Cox proportional hazard models confirmed the statistical significance of the predictors identified. A further analysis was performed to identify cutoffs using a grid search. Seventy-six individuals met the criteria of receiving MRX for ≥48 weeks with laboratory values available at week 48 (W48). The median duration of MRX was 4.7 years (IQR: 1.6–5.8); 16 had events (10 LT, 3 decompensation, 2 death, and 1 surgical biliary diversion). The 6-year event-free survival improved with a clinically meaningful >1-point ItchRO(Obs) reduction from baseline to W48 (88% vs. 57%; p = 0.005), W48 bilirubin < 6.5 mg/dL (90% vs. 43%; p < 0.0001), and W48 serum bile acid < 200 µmol/L (85% vs. 49%; p = 0.001). These parameters were also predictive of 6-year transplant-free survival.

Conclusions::

Improvement in pruritus by 48 weeks, and lower W48 bilirubin and serum bile acid levels were associated with fewer events. These data may help identify potential markers of disease progression for ALGS patients treated with MRX.

Hepatology communications

Safety, tolerability, and efficacy of maralixibat in adults with primary sclerosing cholangitis: Open-label pilot study

Article

Author: Vig, Pamela ; Dorenbaum, Alejandro ; Pockros, Paul J ; McKibben, Andrew ; Levy, Cynthia ; Bowlus, Christopher L ; Chien, Elaine ; Jaecklin, Thomas ; Cheung, Angela C ; Baek, Marshall ; Eksteen, Bertus ; Forman, Lisa M ; Moylan, Cynthia A ; Hirschfield, Gideon M ; Kennedy, Ciara ; Thorburn, Douglas

Background::

Primary sclerosing cholangitis (PSC) is frequently associated with pruritus, which significantly impairs quality of life. Maralixibat is a selective ileal bile acid transporter (IBAT) inhibitor that lowers circulating bile acid (BA) levels and reduces pruritus in cholestatic liver diseases. This is the first proof-of-concept study of IBAT inhibition in PSC.

Methods::

This open-label study evaluated the safety and tolerability of maralixibat ≤10 mg/d for 14 weeks in adults with PSC. Measures of pruritus, biomarkers of BA synthesis, cholestasis, and liver function were also assessed.

Results::

Of 27 enrolled participants, 85.2% completed treatment. Gastrointestinal treatment-emergent adverse events (TEAEs) occurred in 81.5%, with diarrhea in 51.9%. TEAEs were mostly mild or moderate (63.0%); 1 serious TEAE (cholangitis) was considered treatment related. Mean serum BA (sBA) levels decreased by 16.7% (−14.84 µmol/L; 95% CI, −27.25 to −2.43; p = 0.0043) by week 14/early termination (ET). In participants with baseline sBA levels above normal (n = 18), mean sBA decreased by 40.0% (−22.3 µmol/L, 95% CI, −40.38 to −4.3; p = 0.004) by week 14/ET. Liver enzyme elevations were not significant; however, increases of unknown clinical significance in conjugated bilirubin levels were observed. ItchRO weekly sum scores decreased from baseline to week 14/ET by 8.4% (p = 0.0495), by 12.6% (p = 0.0275) in 18 participants with pruritus at baseline, and by 70% (p = 0.0078) in 8 participants with ItchRO daily average score ≥3 at baseline.

Conclusions::

Maralixibat was associated with reduced sBA levels in adults with PSC. In participants with more severe baseline pruritus, pruritus improved significantly from baseline. TEAEs were mostly gastrointestinal related. These results support further investigation of IBAT inhibitors for adults with PSC-associated pruritus. ClinicalTrials.gov: NCT02061540.

154

News (Medical) associated with Maralixibat Chloride

17 Jun 2024

·www.biospace.com

Mirum’s Volixibat Achieves Positive Interim Analyses in VANTAGE PBC and VISTAS PSC Studies

- VANTAGE PBC interim analysis shows 3.8 point reduction from baseline and 2.3 point placebo-adjusted (p=0.0026) reduction in primary endpoint of pruritus - VISTAS PSC interim analysis exceeds efficacy threshold for study continuation - Mirum to host conference call to discuss analyses, today, June 17 at 8:30 a.m. ET/5:30 a.m. PT FOSTER CITY, Calif.--(BUSINESS WIRE)--Mirum Pharmaceuticals, Inc. (Nasdaq: MIRM) today announced interim results from two Phase 2b studies evaluating volixibat, an oral ileal bile acid transporter (IBAT) inhibitor in patients with primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). Interim results from the VANTAGE study evaluating volixibat in patients with PBC demonstrated a statistically significant (-3.82, p<0.0001) improvement in pruritus for volixibat and a placebo-adjusted difference of -2.32 points in the primary endpoint, p=0.0026, as measured by the Adult ItchRO scale. 75% of patients on volixibat achieved a greater than 50% reduction in serum bile acids. In addition, there was a significant improvement in fatigue at week 16 with volixibat compared to placebo. No new safety signals were observed, and adverse events were similar between the 20 mg and 80 mg treatment groups. The most common adverse event was diarrhea (77%) with all cases mild to moderate, and mostly transient; one case resulted in discontinuation. Four patients experienced serious adverse events, including one in the placebo arm. There were no clinically meaningful changes in liver biomarkers. Adult ItchRO Change from Baseline Mean change in Adult ItchRO score* 20 mg (n=10) 80 mg (n=10) 20+80 mg (n=20) PBO (n=10) LSMean (SE) P-value -3.84 (0.609) <0.0001 -3.79 (0.564) <0.0001 -3.82 (0.414) <0.0001 -1.50 (0.585) 0.0149 Difference between VLX and PBO P-value -2.34 0.0090 -2.29 0.0075 -2.32 0.0026 *Adult ItchRO is a 0-10 numerical rating scale; MMRM weekly averaged worst daily itch score, assessed over weeks 17-28 of the treatment period. Based on these results, the VANTAGE PBC trial will continue with a volixibat dose of 20 mg twice daily. Concurrently, the interim analysis for the VISTAS PSC study was conducted and the independent data review committee recommended that the study continue with the selected volixibat dose of 20 mg twice daily, with no changes to the study. The criteria for continuation included safety as well as a predefined threshold for efficacy. The sponsor and investigators are blinded to the interim results and analysis. “The interim data from the VANTAGE study provide outstanding results in relation to what has been shown for treatment of pruritus in PBC,” said Joanne Quan, MD, chief medical officer at Mirum. “With both VISTAS and VANTAGE advancing to enroll their confirmatory portions, we are excited about volixibat as a potential future option to help patients overcome one of the most prevalent and burdensome symptoms of these rare liver diseases.” “The results of the interim analyses are very impressive as they confirm the potential of volixibat in targeting bile acids in PBC and PSC,” said Kris Kowdley, MD, Washington State University and an investigator for VANTAGE and VISTAS. “I look forward to seeing the final data with the goal of having additional therapies available to address the burden of disease in adult cholestasis.” “The symptomatic burden in PBC is significant and often an underappreciated aspect of this disease. Both itch and fatigue are devastating hallmarks of PBC that can significantly decrease quality of life,” said Carol Roberts, president of the PBCers Organization. “It is incredibly encouraging for PBC patients to see such promising results with volixibat.” Conference Call to Discuss Interim Analysis Mirum will be hosting a conference call to discuss the interim analyses from VISTAS and VANTAGE today, Monday, June 17 at 8:30 a.m. ET/5:30 a.m. PT. Join the call by dialing (404) 975-4839 (local/int’l) or (833) 470-1428 (toll-free) and using the access code: 205511. You may also access the webcast through Mirum’s Investor Relations website. About Volixibat Volixibat is an oral, minimally absorbed agent designed to selectively inhibit the ileal bile acid transporter (IBAT). Volixibat may offer a novel approach in the treatment of adult cholestatic diseases by blocking the recycling of bile acids, through inhibition of IBAT, thereby reducing bile acids systemically and in the liver. Phase 1 and Phase 2 studies of volixibat demonstrated on-target fecal bile acid excretion, a pharmacodynamic marker of ASBT inhibition, in addition to decreases in LDL cholesterol and increases in 7αC4 which are markers of bile acid synthesis. Volixibat has been evaluated in more than 400 individuals across multiple clinical trials. The most common adverse events reported were mild to moderate gastrointestinal events observed in the volixibat groups. Volixibat is currently being evaluated in Phase 2b studies for primary sclerosing cholangitis (VISTAS study), and primary biliary cholangitis (VANTAGE study). About Mirum Pharmaceuticals, Inc. Mirum Pharmaceuticals, Inc. is a biopharmaceutical company dedicated to transforming the treatment of rare diseases affecting children and adults. Mirum has three approved medications: LIVMARLI® (maralixibat) oral solution, CHOLBAM® (cholic acid) capsules, and CHENODAL® (chenodiol) tablets. LIVMARLI, an IBAT inhibitor, is approved for the treatment of two rare liver diseases affecting children and adults. It is approved for the treatment of cholestatic pruritus in patients with Alagille syndrome in the U.S. (three months and older), in Europe (two months and older), and in other regions globally. It is also approved in the U.S. in cholestatic pruritus in PFIC patients five years of age and older and in Europe the Committee for Medicinal Products for Human Use (CHMP) has adopted positive opinion of LIVMARLI to treat patients with PFIC three months and older. A decision by the European Commission is expected in the third quarter 2024. CHOLBAM is FDA-approved for the treatment of bile acid synthesis disorders due to single enzyme deficiencies and adjunctive treatment of peroxisomal disorders in patients who show signs or symptoms or liver disease. CHENODAL has received medical necessity recognition by the FDA to treat patients with cerebrotendinous xanthomatosis (CTX). Mirum’s late-stage pipeline includes two investigational treatments for debilitating liver diseases. Volixibat, an IBAT inhibitor, is being evaluated in two potentially registrational studies including the Phase 2b VISTAS study for primary sclerosing cholangitis and Phase 2b VANTAGE study for primary biliary cholangitis. Lastly, CHENODAL has been evaluated in a Phase 3 clinical study, RESTORE, to treat patients with CTX, with positive topline results reported in 2023. To learn more about Mirum, visit mirumpharma.com and follow Mirum on Facebook, LinkedIn, Instagram and Twitter (X). LIVMARLI® (maralixibat) Oral Solution IMPORTANT SAFETY INFORMATION Limitation of Use: LIVMARLI is not for use in PFIC type 2 patients who have a severe defect in the bile salt export pump (BSEP) protein. LIVMARLI can cause side effects, including: Liver injury. Changes in certain liver tests are common in patients with Alagille syndrome and PFIC but can worsen during treatment. These changes may be a sign of liver injury. In PFIC, this can be serious or may lead to liver transplant or death. Your healthcare provider should do blood tests and physical exams 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), bloating in your stomach area, loss of appetite or bleeding or bruising more easily than normal. Stomach and intestinal (gastrointestinal) problems. LIVMARLI can cause stomach and intestinal problems, including diarrhea and stomach pain. Your healthcare provider may advise you to monitor for new or worsening stomach problems including stomach pain, diarrhea, blood in your stool or vomiting. 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 is common in patients with Alagille syndrome and PFIC but may worsen during treatment. Your healthcare provider should do blood tests before starting and during treatment and may monitor for bone fractures and bleeding which have been reported as common side effects. US Prescribing Information EU SmPC Forward-Looking Statements This press release contains “forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Such forward-looking statements include those regarding the clinical potential and regulatory process for volixibat, the ability for volixibat to impact bile acids or pruritus in patients with PSC or PBC, and the effectiveness of volixibat in a real-world population, if ever approved by the FDA. 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,” “could,” “would,” “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. A further description of risks and uncertainties can be found in Mirum’s Annual Report on Form 10-K for the fiscal year ended December 31, 2023 and in its subsequent reports on Form 10-Q, including in the sections thereof captioned “Risk Factors,” as well as in its subsequent reports on Form 8-K, all of which are filed with the U.S. Securities and Exchange Commission and available at .

Clinical ResultPhase 2Drug ApprovalPhase 1Phase 3

16 Jun 2024

·www.biospace.com

Mirum Pharmaceuticals to Host Investor Call to Share Interim Analysis Results from the Volixibat VANTAGE and VISTAS studies on June 17, 2024

FOSTER CITY, Calif.--(BUSINESS WIRE)-- Mirum Pharmaceuticals, Inc. (NASDAQ: MIRM) today announced that it will host an investor call on Monday, June 17 at 8:30 a.m. ET to share interim analysis results from the Volixibat VANTAGE Phase 2b study in primary biliary cholangitis (PBC) and the Volixibat VISTAS Phase 2b study in primary sclerosing cholangitis (PSC). Conference call details: Monday June 17, 2024 8:30 a.m. ET / 5:30 a.m. PT Dial-in: U.S./Toll-Free: +1 833 470 1428 International: +1 404 975 4839 Passcode: 205511 You may also access the call via webcast by visiting the Events & Presentations section on Mirum’s website. A replay of this webcast will be available for 30 days. About Mirum Pharmaceuticals, Inc. Mirum Pharmaceuticals, Inc. is a biopharmaceutical company dedicated to transforming the treatment of rare diseases affecting children and adults. Mirum has three approved medications: LIVMARLI® (maralixibat) oral solution, CHOLBAM® (cholic acid) capsules, and CHENODAL® (chenodiol) tablets. LIVMARLI, an IBAT inhibitor, is approved for the treatment of two rare liver diseases affecting children and adults. It is approved for the treatment of cholestatic pruritus in patients with Alagille syndrome in the U.S. (three months and older), in Europe (two months and older), and in other regions globally. It is also approved in the U.S. in cholestatic pruritus in PFIC patients five years of age and older. LIVMARLI has received positive opinion by CHMP in Europe for the treatment of PFIC in patients three months of age and older. A decision by the European Commission is expected by the third quarter of 2024. CHOLBAM is FDA-approved for the treatment of bile acid synthesis disorders due to single enzyme deficiencies and adjunctive treatment of peroxisomal disorders in patients who show signs or symptoms or liver disease. CHENODAL has received medical necessity recognition by the FDA to treat patients with cerebrotendinous xanthomatosis (CTX). Mirum’s late-stage pipeline includes two investigational treatments for debilitating liver diseases. Volixibat, an IBAT inhibitor, is being evaluated in two potentially registrational studies including the Phase 2b VISTAS study for primary sclerosing cholangitis and Phase 2b VANTAGE study for primary biliary cholangitis. Lastly, CHENODAL has been evaluated in a Phase 3 clinical study, RESTORE, to treat patients with CTX, with positive topline results reported in 2023. To learn more about Mirum, visit mirumpharma.com and follow Mirum on Facebook, LinkedIn, Instagram and Twitter (X). View source version on businesswire.com: Contacts Investors: Andrew McKibben ir@mirumpharma.com Media: Erin Murphy media@mirumpharma.com Source: Mirum Pharmaceuticals, Inc. View this news release online at:

Phase 2Drug ApprovalClinical Result

06 Jun 2024

·www.biospace.com

Long-Term Data from Mirum’s LIVMARLI Studies in ALGS and PFIC Highlighted at EASL Congress

Data showcases sustained clinical benefit following seven years of LIVMARLI treatment in patients with Alagille syndrome Long-term extension data from LIVMARLI PFIC studies highlight improvement in key liver markers and growth FOSTER CITY, Calif.--(BUSINESS WIRE)-- Mirum Pharmaceuticals, Inc. (Nasdaq: MIRM) today announced that data from new analyses showing long-term treatment with LIVMARLI were presented during the European Association for the Study of the Liver (EASL) Annual Congress, June 5-8, 2024, in Milan, Italy. Presentations from studies evaluating LIVMARLI® (maralixibat) oral solution in patients with Alagille syndrome (ALGS) and Progressive Familial Intrahepatic Cholestasis (PFIC) included: THU-094: Clinical Benefits with Maralixibat for Patients with Alagille Syndrome are Durable Through 7 Years of Treatment: Data from the MERGE Study Presented by Doug Mogul, MD, PhD – Mirum Pharmaceuticals, Inc., Foster City, CA, USA An analysis of ALGS studies evaluating LIVMARLI for up to seven years of treatment were presented to demonstrate the durability of response to LIVMARLI across multiple clinical and laboratory outcomes. Data demonstrated that nearly all patients who remained on LIVMARLI for seven years experienced benefit including clinically meaningful reductions in pruritus and serum bile acids, along with improvements in height. View the full presentation. THU-129: Maralixibat Improves Growth in Patients with Progressive Familial Intrahepatic Cholestasis: Data from the MARCH/MARCH-ON Trials Presented by Professor Richard J. Thompson, MD, PhD – King's College, London, UK This analysis reported on the long-term impact of LIVMARLI on improvements in growth across a variety of PFIC types in 60 patients from the All-PFIC cohort of the MARCH/MARCH-ON clinical trials. Patients treated with LIVMARLI from the All-PFIC cohort had a statistically significant improvement in height and weight z-scores which persisted through 82 weeks of treatment. View the full presentation. THU-158: Improvements in Serum Bile Acid Levels are Associated with Improvements in Key Markers of Liver Health After Maralixibat Treatment in Children with Progressive Familial Intrahepatic Cholestasis: Data from the MARCH/MARCH-ON Trials Presented by Lorenzo D’Antiga, MD - Papa Giovanni XXIII Hospital, Bergamo, Italy This analysis aimed to assess correlations between serum bile acid (sBA) improvements and key liver parameters, including bilirubin. These data showed that reductions in sBA after treatment with LIVMARLI are correlated with reductions in bilirubin, a key marker of liver disease. These results indicate the potential for LIVMARLI to have disease modifying effects and improvements in liver health for patients with PFIC. View the full presentation. About LIVMARLI® (maralixibat) oral solution LIVMARLI® (maralixibat) oral solution is an orally administered, once-daily, ileal bile acid transporter (IBAT) inhibitor approved by the U.S. Food and Drug Administration for the treatment of cholestatic pruritus in patients with Alagille syndrome (ALGS) three months of age and older and for progressive familial intrahepatic cholestasis (PFIC) five years of age and older. LIVMARLI is also the only approved IBAT inhibitor approved by the European Commission for the treatment of cholestatic pruritus in patients with ALGS two months and older, and by Health Canada for the treatment of cholestatic pruritus in ALGS. For more information for U.S. residents, please visit LIVMARLI.com. LIVMARLI has received positive opinion by CHMP in Europe for the treatment of PFIC in patients three months of age and older. A decision by the European Commission is expected by the third quarter of 2024. LIVMARLI has received Breakthrough Therapy designation for ALGS and PFIC type 2 and orphan designation for ALGS and PFIC. To learn more about ongoing clinical trials with LIVMARLI, please visit Mirum’s clinical trials section on the company’s website. IMPORTANT SAFETY INFORMATION Limitation of Use: LIVMARLI is not for use in PFIC type 2 patients who have a severe defect in the bile salt export pump (BSEP) protein. LIVMARLI can cause side effects, including: Liver injury. Changes in certain liver tests are common in patients with Alagille syndrome and PFIC but can worsen during treatment. These changes may be a sign of liver injury. In PFIC, this can be serious or may lead to liver transplant or death. Your healthcare provider should do blood tests and physical exams 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), bloating in your stomach area, loss of appetite or bleeding or bruising more easily than normal. Stomach and intestinal (gastrointestinal) problems. LIVMARLI can cause stomach and intestinal problems, including diarrhea and stomach pain. Your healthcare provider may advise you to monitor for new or worsening stomach problems including stomach pain, diarrhea, blood in your stool or vomiting. 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 is common in patients with Alagille syndrome and PFIC but may worsen during treatment. Your healthcare provider should do blood tests before starting and during treatment and may monitor for bone fractures and bleeding which have been reported as common side effects. US Prescribing Information EU SmPC Canadian Product Monograph About Mirum Pharmaceuticals, Inc. Mirum Pharmaceuticals, Inc. is a biopharmaceutical company dedicated to transforming the treatment of rare diseases affecting children and adults. Mirum has three approved medications: LIVMARLI® (maralixibat) oral solution, CHOLBAM® (cholic acid) capsules, and CHENODAL® (chenodiol) tablets. LIVMARLI, an IBAT inhibitor, is approved for the treatment of two rare liver diseases affecting children and adults. It is approved for the treatment of cholestatic pruritus in patients with Alagille syndrome in the U.S. (three months and older), in Europe (two months and older), and in other regions globally. It is also approved in the U.S. in cholestatic pruritus in PFIC patients five years of age and older. LIVMARLI has received positive opinion by CHMP in Europe for the treatment of PFIC in patients three months of age and older. A decision by the European Commission is expected by the third quarter of 2024. CHOLBAM is FDA-approved for the treatment of bile acid synthesis disorders due to single enzyme deficiencies and adjunctive treatment of peroxisomal disorders in patients who show signs or symptoms or liver disease. CHENODAL has received medical necessity recognition by the FDA to treat patients with cerebrotendinous xanthomatosis (CTX). Mirum’s late-stage pipeline includes two investigational treatments for debilitating liver diseases. Volixibat, an IBAT inhibitor, is being evaluated in two potentially registrational studies including the Phase 2b VISTAS study for primary sclerosing cholangitis and Phase 2b VANTAGE study for primary biliary cholangitis. Lastly, CHENODAL has been evaluated in a Phase 3 clinical study, RESTORE, to treat patients with CTX, with positive topline results reported in 2023. To learn more about Mirum, visit mirumpharma.com and follow Mirum on Facebook, LinkedIn, Instagram and Twitter (X). 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 regarding patient growth data while on LIVMARLI, the reliability of long-term data, and the therapeutic potential and/or commercial viability of LIVMARLI in various liver disease indications and in patient populations that are investigational only. 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. The accuracy of such statements is subject to a number of risks, uncertainties and assumptions including, but are not limited to, the following factors: the uncertainties inherent in research and development; the uncertainties inherent in business and financial planning, including, without limitation, risks related to Mirum’s business and prospects, adverse developments in our focused markets, or adverse developments in the U.S. or global regulatory environment or economies generally; the continued impact of COVID-19 on our business, operations and financial results; and competitive developments. Other factors that might cause such a difference include those discussed in the Company’s filings with the SEC. 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. View source version on businesswire.com: Contacts Media Contact: Erin Murphy media@mirumpharma.com Investor Contact: Andrew McKibben investors@mirumphama.com Source: Mirum Pharmaceuticals, Inc. View this news release online at:

Clinical ResultPhase 2Breakthrough TherapyDrug ApprovalOrphan Drug

100 Deals associated with Maralixibat Chloride

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KEGG	Wiki	ATC	Drug Bank
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R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Alagille Syndrome	EU	Mirum Pharmaceuticals, Inc.	09 Dec 2022
Alagille Syndrome	IS	Mirum Pharmaceuticals, Inc.	09 Dec 2022
Alagille Syndrome	LI	Mirum Pharmaceuticals, Inc.	09 Dec 2022
Alagille Syndrome	NO	Mirum Pharmaceuticals, Inc.	09 Dec 2022
Cholestatic pruritus	US	Mirum Pharmaceuticals, Inc.	29 Sep 2021

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
progressive familial intrahepatic cholestasis	NDA/BLA	US	Mirum Pharmaceuticals, Inc.	14 Feb 2023
Biliary Atresia	Phase 2	CN	CANbridge Life Sciences Ltd.	19 May 2021
Pruritus	Phase 2	US	Mirum Pharmaceuticals, Inc.	24 Nov 2014
Pruritus	Phase 2	CA	Mirum Pharmaceuticals, Inc.	24 Nov 2014
Cholangitis, Sclerosing	Phase 2	US	Mirum Pharmaceuticals, Inc.	01 Mar 2014
Cholangitis, Sclerosing	Phase 2	CA	Mirum Pharmaceuticals, Inc.	01 Mar 2014
Cholangitis, Sclerosing	Phase 2	GB	Mirum Pharmaceuticals, Inc.	01 Mar 2014
Cholestatic liver disease	Phase 2	GB	Mirum Pharmaceuticals, Inc.	01 Aug 2013
Primary Biliary Cholangitis	Phase 2	US	Mirum Pharmaceuticals, Inc.	01 Aug 2013
Primary Biliary Cholangitis	Phase 2	CA	Mirum Pharmaceuticals, Inc.	01 Aug 2013

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


MARCH-ON (Biospace) Manual	Not Applicable	progressive familial intrahepatic cholestasis	-	LIVMARLI	ldppafpcum(yekzlsyppo) = in pruritus severity, serum bile acid (sBA) levels, total bilirubin and growth following up to two years of LIVMARLI treatment. Similar improvements in pruritus and sBA were seen in patients originally randomized to placebo who received LIVMARLI in the open-label study. uwepunrnbg (farbqccqvj )	Positive	18 May 2024
NCT03905330 (MARCH-PFIC, Pubmed)	Phase 3	progressive familial intrahepatic cholestasis biallelic, non-truncated BSEP deficiency \| biallelic FIC1 \| MDR3 ... View more	125	Maralixibat	isnjcrckuu(rdtxbwnjzw) = qrofzorkpf gmgfcawhke (kurssklpot, -257 to -94)	Positive	06 May 2024
				Placebo	isnjcrckuu(rdtxbwnjzw) = flddbuwzac gmgfcawhke (kurssklpot, -58 to 80)
EMBARK (BusinessWire) Manual	Phase 2	Biliary Atresia	-	LIVMARLI	ghibsynxzj(rncaemmoud) = The study did not meet its primary endpoint of mean change in bilirubin from baseline to Week 26 aghzxdavao (hyofkixwju ) Not Met View more	Negative	18 Dec 2023
				placebo
MARCH (AASLD2023) Manual	Phase 3	progressive familial intrahepatic cholestasis	8	maralixibat 570µg/kg	yykkkrezlq(rbllzmqefb) = flutiubsoe dzkgvudpei (ndgbaprput ) View more	Positive	23 Nov 2023
				placebo	yykkkrezlq(rbllzmqefb) = gsfrrbeuij dzkgvudpei (ndgbaprput ) View more
MARCH-PFIC (AASLD2023) Manual	Phase 3	progressive familial intrahepatic cholestasis	11	maralixibat (TJP2 deficiency)	eyoawtlrgo(zeqcpwulkq) = Safety signals were consistent with other PFIC types. kooefsghlo (zpoaaxoiaj ) View more	Positive	13 Nov 2023
				placebo (TJP2 deficiency)
MARCH-PFIC (AASLD2023) Manual	Phase 3	progressive familial intrahepatic cholestasis	64	maralixibat	kvthwpnvqw(rogfspvtgs) = ftkxvupucs ottkzfqygu (glkdxtyjqg )	Positive	13 Nov 2023
				placebo	kvthwpnvqw(rogfspvtgs) = mddqnyeomg ottkzfqygu (glkdxtyjqg )
AASLD2023	Not Applicable	Arthrogryposis Renal Dysfunction Cholestasis Syndrome	-	Maralixibat	heqbflldby(eopwsvgvro) = dorqjweogt nalonpssjr (eqsskwqexp ) View more	-	10 Nov 2023
MARCH-ON (EASL2023)	Phase 3	progressive familial intrahepatic cholestasis Maintenance	-	MRX-MRX group	gxuzwvnzwq(tanoexshxx) = kfpkusvtyk cskezeopfp (sxznexdvro ) View more	-	21 Jun 2023
				PBO-MRX group	gxuzwvnzwq(tanoexshxx) = ubwrhtinon cskezeopfp (sxznexdvro ) View more
MARCH-PFIC (EASL2023)	Phase 3	progressive familial intrahepatic cholestasis	93	Maralixibat 570 μg/kg twice daily	xhcktmpvqk(ucdvijrocf) = Abdominal pain was also mostly mild and transient and, in nearly all instances, was concurrent with diarrhea. vntjjtfyzc (rhjgqyqypd ) View more	-	21 Jun 2023
				Placebo
EASL2023	Not Applicable	Alagille Syndrome	14	Maralixibat	qytmrjowag(wbosiynats) = aqmlgngiyo cbrmthzvio (dxnoozpxnw ) View more	-	21 Jun 2023

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