Randomized Double-Blind Placebo-Controlled Phase 3 Study to Evaluate the Efficacy and Safety of Maralixibat in the Treatment of Participants with Cholestatic Pruritus

The purpose of this study is to determine whether the investigational treatment (maralixibat) is safe and effective in pediatric and adult participants who have cholestatic liver disease with pruritus that has been refractory to other therapies, and who have no other treatment options.

Start Date14 Oct 2024

Sponsor / Collaborator

Mirum Pharmaceuticals, Inc.

NCT06413368 / Not yet recruitingPhase 2/3IIT

Maralixibat in Patients With Cystic Fibrosis and Constipation, A Within-Subjects Pilot Study

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.

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

14 Nov 2024·JOURNAL OF MEDICINAL CHEMISTRY

Structure–Activity Relationships and Target Selectivity of Phenylsulfonylamino-Benzanilide Inhibitors Based on S1647 at the SLC10 Carriers ASBT, NTCP, and SOAT

Article

Author: Neubauer, Anita ; Fühler, Bärbel ; Lotz, Philipp ; Daude, Michael ; Geyer, Joachim ; Neelen, Christopher ; Diederich, Wibke E. ; Wannowius, Marie

The intestinal bile acid carrier ASBT (SLC10A2), the hepatic bile acid carrier NTCP (SLC10A1), and the steroid sulfate carrier SOAT (SLC10A6), all members of the solute carrier family SLC10, are established drug targets. The ASBT inhibitors odevixibat, maralixibat, and elobixibat are used to treat intrahepatic cholestasis, cholestatic pruritus, and obstipation. The peptide drug bulevirtide blocks binding of the hepatitis B and D viruses to NTCP and thereby inhibits the virus's entry into hepatocytes. Experimental SOAT inhibitors have antiproliferative effects on hormone-dependent breast cancer cells. The phenylsulfonylamino-benzanilide S1647 is an inhibitor of ASBT and SOAT. The present study aimed to comparatively analyze a set of newly synthesized and commercially available S1647 derivatives for their transport inhibition against ASBT, NTCP, and SOAT. Structure-activity relationships were systematically analyzed regarding potency and target specificity to elucidate whether this compound class is worth being further developed in preclinical studies for pharmacological ASBT, NTCP, and/or SOAT inhibition.

04 Oct 2024·JOURNAL OF ORGANIC CHEMISTRY

Stereoselective Synthesis of Maralixibat via VO(acac)₂/Schiff Base-Catalyzed Asymmetric Oxidation of Its Sulfide Intermediate

Article

Author: Peng, Ziyu ; Mpofo, Mercy ; Ye, Long ; Jie, Zheng

The stereoselective synthesis of maralixibat was achieved by harnessing the chiral transferring effect of the stereogenic R-sulfoxide functionality, which was obtained via the VO(acac)₂/Schiff base-catalyzed asymmetric oxidation of a phenylthiophenol prochiral intermediate. The R-sulfoxide intermediate underwent a ring closure reaction to form the seven-membered ring core structure with the desired stereochemistry, ultimately ensuring the drug's exceptional isomeric purity and synthetic efficiency.

20 Sep 2024·Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology

[Progress in the treatment of progressive familial intrahepatic cholestasis].

Review

Author: Liu, T ; Wang, J S

Progressive familial intrahepatic cholestasis (PFIC) is an important cause of liver-related death or transplantation in children. The PFIC spectrum is expanding, twelve types of PFIC are currently included in the Online Mendelian Inheritance in Man (OMIM) database. With the increase of PFIC types and the inconsistence of certain types in numbering, the current numbering classification of PFIC is confusing, so the experts in the field recommend using the corresponding mutant gene/ protein defect to name different type of PFIC except for PFIC type 1-3. The clarification of the genotype-phenotype relationship and/or the establishment of phenotypic predictors significantly improved the management of patients with PFIC. Odevixibat and maralixibat, inhibitors of the apical sodium ion-dependent bile acid transporter on the intestinal epithelial cells, were approved in European Union and the United States for the treatment of PFIC pruritus in 2021, expanding the treatment options for PFIC. Additionally, personalized treatments for specific mutations and novel gene therapy is promising.

163

News (Medical) associated with Maralixibat Chloride

14 Nov 2024

·www.businesswire.com

Mirum Pharmaceuticals to Showcase Data from its LIVMARLI and Volixibat Clinical Programs at AASLD’s The Liver Meeting

FOSTER CITY, Calif.--( BUSINESS WIRE )--Mirum Pharmaceuticals, Inc. (NASDAQ: MIRM) today announced that it will present data at the American Association for the Study of Liver Disease’s (AASLD) The Liver Meeting®, taking place November 15-19, 2024, in San Diego, California. Enclosed below are the titles that have been accepted for presentation during the meeting. The abstracts are available via the AASLD website . Full analyses will be available following their presentation within the Publications & Presentation section on Mirum’s website . Presentations Abstract #5038: Volixibat for Cholestatic Pruritus in Primary Biliary Cholangitis: An Adaptive, Randomized, Placebo-controlled Phase 2b Trial (VANTAGE): Interim Results **Late-breaker poster presentation** Monday, November 18 from 1:00-2:00pm, Poster Hall C Presented by Dr. Kris Kowdley, Washington State University, Seattle, Washington, USA Abstract #184: Improvements in Pruritus are Associated with Improvements in Growth in Patients with Progressive Familial Intrahepatic Cholestasis: Data from the MARCH-ON trial **Oral presentation** Sunday, November 17 from 12:15-12:30pm during the ‘Advances in Pediatric Liver Disease’ session, Ballroom 6C Presented by Dr. Alexander Miethke, Cincinnati Children’s Hospital, Cincinnati, Ohio, USA Abstract #4347: Pilot Study of Volixibat Co-administered with OCA for Primary Biliary Cholangitis (PBC) Treatment: The VLX-602 Trial Monday, November 18 from 1:00-2:00pm during Poster Session IV, Poster Hall C Presented by Dr. Kris Kowdley, Washington State University, Seattle, Washington, USA Abstract #4400: Impact of Maralixibat on Caregiver Burden for Patients with Alagille Syndrome and Progressive Familial Intrahepatic Cholestasis Monday, November 18 from 1:00-2:00pm during Poster Session IV, Poster Hall C Presented by Dr. Natasha Dilwali, The Johns Hopkins School of Medicine, Baltimore, Maryland, USA Abstract #4419 : Real-world Use of Maralixibat in Biliary Atresia: A Case Series Monday, November 18 from 1:00-2:00pm during Poster Session IV, Poster Hall C Presented by Dr. Natasha Dilwali, The Johns Hopkins School of Medicine, Baltimore, Maryland, USA Abstract #4432: The Relationship Between Serum Bile Acids and Event-Free Survival Following the Use of Maralixibat for Progressive Familial Intrahepatic Cholestasis: Data from MARCH/MARCH-ON Monday, November 18 from 1:00-2:00pm during Poster Session IV, Poster Hall C Presented by Professor Richard Thompson, King’s College London, United Kingdom Abstract #4436: Bile Acid Subspecies are Correlated with Pruritus and Bilirubin Improvement in PFIC Patients Treated with Maralixibat: Data from MARCH and MARCH-ON Monday, November 18 from 1:00-2:00pm during Poster Session IV, Poster Hall C Presented by Professor Henkjan Verkade, University of Groningen, Groningen, Netherlands Alagille Syndrome Patient & Physician Fireside Discussion During the meeting, Mirum will host a session spotlighting a pediatric hepatologist and an adult patient living with ALGS. Dr. Ajay Jain, St. Louis University, will discuss clinical insights and patient, Emma, will share her experience with LIVMARLI. Sunday, November 17 from 1:30-2:00 p.m. in Exhibit Hall TLM Theater #2 About LIVMARLI® (maralixibat) oral solution LIVMARLI® (maralixibat) oral solution is an orally administered, ileal bile acid transporter (IBAT) inhibitor approved by the U.S. Food and Drug Administration for two pediatric cholestatic liver diseases. It is approved for the treatment of cholestatic pruritus in patients with Alagille syndrome (ALGS) in the U.S. three months of age and older and in Europe for patients two months of age and older. It is also approved in the U.S. for the treatment of cholestatic pruritus in patients with progressive familial intrahepatic cholestasis (PFIC) 12 months of age and older and in Europe for the treatment of PFIC in patients three months of age and older. For more information for U.S. residents, please visit LIVMARLI.com . 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 12 months of age and older; in Europe, it is approved for patients with PFIC three months of age and older. Mirum is also initiating the Phase 3 EXPAND study, a label expansion opportunity for LIVMARLI in additional settings of cholestatic pruritus. 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 2 VISTAS study for primary sclerosing cholangitis (PSC) and Phase 2b VANTAGE study for primary biliary cholangitis. Volixibat has been granted Breakthrough Therapy Designation for the treatment of cholestatic pruritus in patients with PBC. Lastly, chenodiol, has been evaluated in a Phase 3 clinical study, RESTORE, to treat patients with CTX, with positive topline results reported in 2023. Mirum has submitted a new drug application with the FDA for the approval of chenodiol to treat CTX in the U.S. 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 for both commercial and clinical programs, which may include discussion of the Company’s clinical and research data relating to the therapeutic potential and/or commercial viability of LIVMARLI or other Company product candidates in various liver disease indications and in patient populations that are investigational only. 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 and the other risks described in Mirum’s filings with the Securities and Exchange Commission. 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 www.sec.gov .

Phase 2Breakthrough TherapyDrug ApprovalOrphan DrugPhase 3

31 Oct 2024

·ir.mirumpharma.com

Mirum Pharmaceuticals to Showcase LIVMARLI Data from its ALGS and PFIC Programs at the NASPGHAN Annual Meeting

FOSTER CITY, Calif.--(BUSINESS WIRE)-- Mirum Pharmaceuticals, Inc. (NASDAQ: MIRM) today announced its participation in the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) annual meeting taking place November 6-9, 2024, in Hollywood, Florida. Data highlighting clinical benefit and real-world evidence for patients with Alagille syndrome (ALGS) and Progressive Familial Intrahepatic Cholestasis (PFIC), treated with LIVMARLI® (maralixibat) oral solution, will be presented during the meeting. Highlighted below are the titles that have been accepted for presentation during the meeting. The abstracts are available via the NASPGHAN Program Book. Full analyses will be available following their presentation within the Publications & Presentations section on Mirum’s website. Abstract 77: Maralixibat improves growth in patients with progressive familial intrahepatic cholestasis: Data from the MARCH/MARCH-ON trials Thursday, November 7 between 5:00-7:00 p.m. ET during Poster Session I Presented by Dr. Amal Aqul Abstract 361: Clinical benefits of maralixibat for patients with Alagille syndrome are durable through 7 years of treatment: Data from the MERGE study Friday, November 8 between 12:00-2:00 p.m. ET during Poster Session II Presented by Dr. Karen Murray Abstract 637: Improvements in serum bile acids are associated with improvements in markers of liver health after maralixibat treatment in children with PFIC: Data from the MARCH/MARCH-ON trials Saturday, November 9 between 12:00-2:00 p.m. ET during Poster Session III Presented by Dr. Alexander Miethke Abstract 638: Improvements in pruritus after maralixibat treatment are associated with improved health-related quality of life for patients with cholestatic liver disease Saturday, November 9 between 12:00-2:00 p.m. ET during Poster Session III Presented by Dr. Alexander Miethke Abstract 664: Long-term maralixibat impact on concomitant medication use for the treatment of cholestatic pruritus in Alagille syndrome: Real-world experience in the United States Saturday, November 9 between 12:00-2:00 p.m. ET during Poster Session III Presented by Dr. Jolan Terner-Rosenthal About LIVMARLI® (maralixibat) oral solution LIVMARLI® (maralixibat) oral solution is an orally administered, ileal bile acid transporter (IBAT) inhibitor approved by the U.S. Food and Drug Administration for two pediatric cholestatic liver diseases. It is approved for the treatment of cholestatic pruritus in patients with Alagille syndrome (ALGS) in the U.S. three months of age and older and in Europe for patients two months of age and older. It is also approved in the U.S. for the treatment of cholestatic pruritus in patients with progressive familial intrahepatic cholestasis (PFIC) 12 months of age and older and in Europe for the treatment of PFIC in patients three months of age and older. For more information for U.S. residents, please visit LIVMARLI.com. 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 12 months of age and older; in Europe, it is approved for patients with PFIC three months of age and older. Mirum is also initiating the Phase 3 EXPAND study, a label expansion opportunity for LIVMARLI in additional settings of cholestatic pruritus. 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 2 VISTAS study for primary sclerosing cholangitis (PSC) and Phase 2b VANTAGE study for primary biliary cholangitis. Volixibat has been granted Breakthrough Therapy Designation for the treatment of cholestatic pruritus in patients with PBC. Lastly, chenodiol, has been evaluated in a Phase 3 clinical study, RESTORE, to treat patients with CTX, with positive topline results reported in 2023. Mirum has submitted a new drug application with the FDA for the approval of chenodiol to treat CTX in the U.S. 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 relating to 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,” “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 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 www.sec.gov. Media Contact: Erin Murphy media@mirumpharma.com Investor Contact: Andrew McKibben ir@mirumphama.com

Phase 2Breakthrough TherapyDrug ApprovalPhase 3Orphan Drug

10 Oct 2024

·ir.mirumpharma.com

Volixibat Granted Breakthrough Therapy Designation for Cholestatic Pruritus in Primary Biliary Cholangitis

- Designation based on positive interim analysis of Phase 2b VANTAGE study FOSTER CITY, Calif.--(BUSINESS WIRE)-- Mirum Pharmaceuticals, Inc. (Nasdaq: MIRM) today announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation to volixibat as a potential treatment for cholestatic pruritus in patients with primary biliary cholangitis (PBC). The regulatory designation is based on the positive interim analysis of the Phase 2b VANTAGE study which showed statistically significant improvement versus placebo in pruritus for patients treated with volixibat. The confirmatory portion of the study is ongoing with completion of enrollment expected in 2026. “Breakthrough Therapy Designation for volixibat in PBC underscores the importance and urgency for a treatment to address one of the most burdensome impacts of this rare liver disease,” said Joanne Quan, MD, chief medical officer at Mirum. “We look forward to advancing our VANTAGE study with the goal of making volixibat available to patients living with PBC-related itch as quickly as possible.” The FDA’s Breakthrough Therapy Designation aims to expedite the development and review of drugs that are intended to treat serious or life-threatening diseases. To qualify for this designation, preliminary clinical evidence must indicate that the drug may demonstrate substantial improvement over existing therapy on at least one clinically significant endpoint. 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. Volixibat is currently being evaluated in Phase 2b studies for primary sclerosing cholangitis (VISTAS study), and primary biliary cholangitis (VANTAGE study). In June, Mirum announced positive interim results from the Phase 2b VANTAGE study showing statistically significant improvement in pruritus as well as meaningful reductions in serum bile acids and improvements in fatigue for patients treated with volixibat. No new safety signals were observed, and the most common adverse event was diarrhea with all cases mild to moderate. 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 12 months of age and older; in Europe, it is approved for patients with PFIC three months of age and older. Mirum is also initiating the Phase 3 EXPAND study, a label expansion opportunity for LIVMARLI in additional settings of cholestatic pruritus. 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 2 VISTAS study for primary sclerosing cholangitis (PSC) and Phase 2b VANTAGE study for primary biliary cholangitis. Volixibat has been granted Breakthrough Therapy Designation for the treatment of cholestatic pruritus in patients with PBC. Lastly, chenodiol, has been evaluated in a Phase 3 clinical study, RESTORE, to treat patients with CTX, with positive topline results reported in 2023. Mirum has submitted a new drug application with the FDA for the approval of chenodiol to treat CTX in the U.S. To learn more about Mirum, visit mirumpharma.com and follow Mirum on Facebook, LinkedIn, Instagram and Twitter (X). Forward-Looking Statements Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements include statements regarding, among other things, the results, conduct, progress and timing of Mirum’s clinical trials and the review and approval process by regulatory authorities of its product candidates . 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 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 www.sec.gov. Media Contact: Erin Murphy media@mirumpharma.com Investor Contact: Andrew McKibben ir@mirumphama.com

Phase 2Drug ApprovalClinical ResultBreakthrough TherapyPhase 3

100 Deals associated with Maralixibat Chloride

External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB16226

R&D Status

Approved

10 top approved records.

to view more data

Indication	Country/Location	Organization	Date
progressive familial intrahepatic cholestasis	EU	Mirum Pharmaceuticals, Inc.	08 Jul 2024
progressive familial intrahepatic cholestasis	IS	Mirum Pharmaceuticals, Inc.	08 Jul 2024
progressive familial intrahepatic cholestasis	LI	Mirum Pharmaceuticals, Inc.	08 Jul 2024
progressive familial intrahepatic cholestasis	NO	Mirum Pharmaceuticals, Inc.	08 Jul 2024
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.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Cholestatic liver disease	Phase 3	US	Mirum Pharmaceuticals, Inc.	14 Oct 2024
Cholestatic liver disease	Phase 3	BR	Mirum Pharmaceuticals, Inc.	14 Oct 2024
Cholestatic liver disease	Phase 3	FR	Mirum Pharmaceuticals, Inc.	14 Oct 2024
Cholestatic liver disease	Phase 3	DE	Mirum Pharmaceuticals, Inc.	14 Oct 2024
Cholestatic liver disease	Phase 3	IT	Mirum Pharmaceuticals, Inc.	14 Oct 2024
Cholestatic liver disease	Phase 3	LB	Mirum Pharmaceuticals, Inc.	14 Oct 2024
Cholestatic liver disease	Phase 3	MX	Mirum Pharmaceuticals, Inc.	14 Oct 2024
Cholestatic liver disease	Phase 3	PL	Mirum Pharmaceuticals, Inc.	14 Oct 2024
Cholestatic liver disease	Phase 3	ES	Mirum Pharmaceuticals, Inc.	14 Oct 2024
Cholestatic liver disease	Phase 3	GB	Mirum Pharmaceuticals, Inc.	14 Oct 2024

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05543174 (CTgov)	Phase 3	Alagille Syndrome	7	TAK-625	llgnewolfl(gtbrkmjndq) = hxpchbnwey bazalytdxx (wmvrhjvhkx, tbfahwyxxs - vpqdfiskvr) View more	-	15 Oct 2024
NCT05543187 (CTgov)	Phase 3	progressive familial intrahepatic cholestasis	5	TAK-625 (Primary Cohort: TAK-625)	xjlpdhifjj(nodgbkhfhi) = uksujplcrn olndnsatlo (nbzvnlhzqu, arahazftdo - xrryffyvio) View more	-	24 Sep 2024
				TAK-625 (Supplemental Cohort: TAK-625)	xjlpdhifjj(nodgbkhfhi) = dazfpejtsm olndnsatlo (nbzvnlhzqu, phnpwefwdy - fbrapiaeqp) View more
MARCH-ON (Biospace) Manual	Not Applicable	progressive familial intrahepatic cholestasis	-	LIVMARLI	stymdaluuz(hhhhwkajkh) = 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. ibcsatlcap (wlwzpcfgby )	Positive	18 May 2024
NCT03905330 (MARCH-PFIC, Pubmed) Manual	Phase 3	progressive familial intrahepatic cholestasis biallelic, non-truncated BSEP deficiency \| biallelic FIC1 \| MDR3 ... View more	93	Maralixibat	vvtxfbzkjc(agzagavfkq) = vjznlnttqz xykgceervo (mflrjvozkb ) View more	Positive	06 May 2024
				Placebo	cckraqejex(emruewkjcl) = trovnzgtem mqudazqgai (rvfwceiqqh ) View more
EMBARK (BusinessWire) Manual	Phase 2	Biliary Atresia	-	LIVMARLI	susehogvzc(aqboeapcxn) = The study did not meet its primary endpoint of mean change in bilirubin from baseline to Week 26 qwqhjyqjdx (shvwswuafp ) Not Met View more	Negative	18 Dec 2023
				placebo
MARCH (AASLD2023) Manual	Phase 3	progressive familial intrahepatic cholestasis	8	maralixibat 570µg/kg	horanjyqgm(khaconaamy) = eugkzrgaaf emcolqfzuh (yuktfaucuy ) View more	Positive	23 Nov 2023
				placebo	horanjyqgm(khaconaamy) = ztlxstwied emcolqfzuh (yuktfaucuy ) View more
MARCH-PFIC (AASLD2023) Manual	Phase 3	progressive familial intrahepatic cholestasis	64	maralixibat	xifzoodavs(nkfhzhuctx) = ltlojmzhra mlwbhwslft (drxpbzdzpb )	Positive	13 Nov 2023
				placebo	xifzoodavs(nkfhzhuctx) = bwworymsjy mlwbhwslft (drxpbzdzpb )
MARCH-PFIC (AASLD2023) Manual	Phase 3	progressive familial intrahepatic cholestasis	11	maralixibat (TJP2 deficiency)	dgsexphwig(fjxbqwudgj) = Safety signals were consistent with other PFIC types. ulzfozrcyg (rpyopmpzyu ) View more	Positive	13 Nov 2023
				placebo (TJP2 deficiency)
AASLD2023	Not Applicable	Arthrogryposis Renal Dysfunction Cholestasis Syndrome	-	Maralixibat	wlopnwbwib(bwxaotxrep) = jgebnmwixx aetuxhrcdj (zoqnxlpjwh ) View more	-	10 Nov 2023
MARCH-PFIC (EASL2023)	Phase 3	progressive familial intrahepatic cholestasis	93	Maralixibat 570 μg/kg twice daily	eqfflxnwza(fpytxwblsm) = Abdominal pain was also mostly mild and transient and, in nearly all instances, was concurrent with diarrhea. clbmirtncr (tpqfbnhxik ) View more	-	21 Jun 2023
				Placebo

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