A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Volixibat in the Treatment of Cholestatic Pruritus in Patients With Primary Biliary Cholangitis

The purpose of this clinical research study is to learn more about the use of the study medicine, volixibat, for the treatment of pruritus (itching) associated with Primary Biliary Cholangitis (PBC), and to assess the possible impact on the disease progression of PBC.

Start Date22 Sep 2021

Sponsor / Collaborator

Mirum Pharmaceuticals, Inc.

NCT04718961 / TerminatedPhase 2

A Phase 2a/2b Randomized Double-Blind Placebo-Controlled Study to Evaluate the Efficacy and Safety of Volixibat in Adult Women With Intrahepatic Cholestasis of Pregnancy and Elevated Serum Bile Acid Concentrations (OHANA).

Part 1 is an open-label randomized study of volixibat in patients with Intrahepatic Cholestasis of Pregnancy (ICP) and elevated serum bile acid concentrations (sBA) to evaluate safety and tolerability of two doses of volixibat. Part 2 is a double-blind, placebo controlled, study designed to evaluate the safety and efficacy of a selected volixibat dose.

Start Date04 Jan 2021

Sponsor / Collaborator

Mirum Pharmaceuticals, Inc.

NCT04663308 / RecruitingPhase 2

A Randomized Double-Blind Placebo-Controlled Study to Evaluate the Efficacy and Safety of Volixibat in the Treatment of Cholestatic Pruritus in Patients With Primary Sclerosing Cholangitis

The purpose of this clinical research study is to learn more about the use of the study medicine, volixibat, for the treatment of pruritus (itching) associated with Primary Sclerosing Cholangitis (PSC), and to assess the possible impact on the disease progression of PSC.

Start Date18 Dec 2020

Sponsor / Collaborator

Mirum Pharmaceuticals, Inc.

100 Clinical Results associated with Volixibat potassium ethanolate hydrate

100 Translational Medicine associated with Volixibat potassium ethanolate hydrate

100 Patents (Medical) associated with Volixibat potassium ethanolate hydrate

Literatures (Medical) associated with Volixibat potassium ethanolate hydrate

01 Aug 2020·Journal of hepatologyQ1 · MEDICINE

Volixibat in adults with non-alcoholic steatohepatitis: 24-week interim analysis from a randomized, phase II study

Q1 · MEDICINE

Article

Author: Aasim Sheikh ; Parvez Mantry ; Philip N Newsome ; Melissa Palmer ; Tarek Hassanein ; Hak-Myung Lee ; Bradley Freilich ; Harry Sarles ; Muhammad Y Sheikh ; Robert Herring ; Zeid Kayali ; Guruprasad P Aithal

BACKGROUND & AIMS:

Volixibat is an inhibitor of the apical sodium-dependent bile acid transporter (ASBT) that has been hypothesized to improve non-alcoholic steatohepatitis (NASH) by blocking bile acid reuptake and stimulating hepatic bile acid production. We studied the safety, tolerability and efficacy of volixibat in patients with NASH.

METHODS:

In this double-blind, phase II dose-finding study, adults with ≥5% steatosis and NASH without cirrhosis (N = 197) were randomized to receive volixibat (5, 10 or 20 mg) or placebo once daily for 48 weeks. The endpoints of a predefined interim analysis (n = 80), at week 24, were: ≥5% reduction in MRI-proton density fat fraction and ≥20% reduction in serum alanine aminotransferase levels. The primary endpoint was a ≥2-point reduction in non-alcoholic fatty liver disease activity score without worsening fibrosis at week 48.

RESULTS:

Volixibat did not meet either interim endpoint; the study was terminated owing to lack of efficacy. In participants receiving any volixibat dose, mean serum 7-alpha-hydroxy-4-cholesten-3-one (C4; a biomarker of bile acid synthesis) increased from baseline to week 24 (+38.5 ng/ml [SD 53.18]), with concomitant decreases in serum total cholesterol (-14.5 mg/dl [SD 28.32]) and low-density lipoprotein cholesterol (-16.1 mg/dl [SD 25.31]). These changes were generally dose-dependent. On histological analysis, a greater proportion of participants receiving placebo (38.5%, n = 5/13) than volixibat (30.0%, n = 9/30) met the primary endpoint. Treatment-emergent adverse events (TEAEs) were mainly mild or moderate. No serious TEAEs were related to volixibat. Diarrhoea was the most common TEAE overall and the most common TEAE leading to discontinuation.

CONCLUSIONS:

Increased serum C4 and decreased serum cholesterol levels provide evidence of target engagement. However, inhibition of ASBT by volixibat did not elicit a liver-related therapeutic benefit in adults with NASH.

LAY SUMMARY:

A medicine called volixibat has previously been shown to reduce cholesterol levels in the blood. This study investigated whether volixibat could reduce the amount of fat in the liver and reduce liver injury in adults with an advanced form of non-alcoholic fatty liver disease. Volixibat did not reduce the amount of fat in the liver, nor did it have any other beneficial effect on liver injury. Participants in the study generally tolerated the side effects of volixibat and, as in previous studies, the main side effect was diarrhoea. These results show that volixibat is not an effective treatment for people with fatty liver disease.

CLINICAL TRIAL IDENTIFIER:

NCT02787304.

01 Dec 2018·BMC gastroenterology

Safety, tolerability and pharmacodynamics of apical sodium-dependent bile acid transporter inhibition with volixibat in healthy adults and patients with type 2 diabetes mellitus: a randomised placebo-controlled trial

Article

Author: van Vliet, Andre A ; Dorenbaum, Alejandro ; Levin, Nancy ; Palmer, Melissa ; Tiessen, Renger G ; Kennedy, Ciara A ; Gedulin, Bronislava ; Keller, Bradley T ; Acevedo, Lisette

BACKGROUND:

Pathogenesis in non-alcoholic steatohepatitis (NASH) involves abnormal cholesterol metabolism and hepatic accumulation of toxic free cholesterol. Apical sodium-dependent bile acid transporter (ASBT) inhibition in the terminal ileum may facilitate removal of free cholesterol from the liver by reducing recirculation of bile acids (BAs) to the liver, thereby stimulating new BA synthesis from cholesterol. The aim of this phase 1 study in adult healthy volunteers (HVs) and patients with type 2 diabetes mellitus (T2DM) was to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of ASBT inhibition with volixibat (SHP626; formerly LUM002).

METHODS:

Participants were randomised 3:1 to receive once-daily oral volixibat (0.5 mg, 1 mg, 5 mg or 10 mg) or placebo for 28 days in two cohorts (HV and T2DM). Assessments included safety, faecal BA and serum 7α-hydroxy-4-cholesten-3-one (C4; BA synthesis biomarker).

RESULTS:

Sixty-one individuals were randomised (HVs: placebo, n = 12; volixibat, n = 38; T2DM: placebo, n = 3; volixibat, n = 8). No deaths or treatment-related serious adverse events were reported. Mild or moderate gastrointestinal adverse events were those most frequently reported with volixibat. With volixibat, mean total faecal BA excretion on day 28 was ~1.6-3.2 times higher in HVs (643.73-1239.3 μmol/24 h) and ~8 times higher in T2DM (1786.0 μmol/24 h) than with placebo (HVs: 386.93 μmol/24 h; T2DM: 220.00 μmol/24 h). With volixibat, mean C4 concentrations increased by ~1.3-5.3-fold from baseline to day 28 in HVs and by twofold in T2DM.

CONCLUSIONS:

Volixibat was generally well tolerated. Increased faecal BA excretion and serum C4 levels support the mechanistic rationale for exploring ASBT inhibition in NASH. The study was registered with the Dutch clinical trial authority (Centrale Commissie Mensgebonden Onderzoek; trial registration number NL44732.056.13; registered 24 May 2013).

16 Mar 2018·BMC Pharmacology & Toxicology

A randomised, double-blind, placebo-controlled phase 1 study of the safety, tolerability and pharmacodynamics of volixibat in overweight and obese but otherwise healthy adults: implications for treatment of non-alcoholic steatohepatitis.

Article

Author: Jennings, Lee ; Bliss, Caleb ; Martin, Patrick ; Silberg, Debra G ; Palmer, Melissa

BACKGROUND:

Accumulation of toxic free cholesterol in hepatocytes may cause hepatic inflammation and fibrosis. Volixibat inhibits bile acid reuptake via the apical sodium bile acid transporter located on the luminal surface of the ileum. The resulting increase in bile acid synthesis from cholesterol could be beneficial in patients with non-alcoholic steatohepatitis. This adaptive dose-finding study investigated the safety, tolerability, pharmacodynamics, and pharmacokinetics of volixibat.

METHODS:

Overweight and obese adults were randomised 3:1 to double-blind volixibat or placebo, respectively, for 12 days. Volixibat was initiated at a once-daily dose of 20 mg, 40 mg or 80 mg. Based on the assessment of predefined safety events, volixibat dosing was either escalated or reduced. Other dose regimens (titrations and twice-daily dosing) were also evaluated. Assessments included safety, tolerability, stool hardness, faecal bile acid (FBA) excretion, and serum levels of 7α-hydroxy-4-cholesten-3-one (C4) and lipids.

RESULTS:

All 84 randomised participants (volixibat, 63; placebo, 21) completed the study, with no serious adverse events at doses of up to 80 mg per day (maximum assessed dose). The median number of daily bowel evacuations increased from 1 (range 0-4) to 2 (0-8) during volixibat treatment, and stool was looser with volixibat than placebo. Volixibat was minimally absorbed; serum levels were rarely quantifiable at any dose or sampling time point, thereby precluding pharmacokinetic analyses. Mean daily FBA excretion was 930.61 μmol (standard deviation [SD] 468.965) with volixibat and 224.75 μmol (195.403) with placebo; effects were maximal at volixibat doses ≥20 mg/day. Mean serum C4 concentrations at day 12 were 98.767 ng/mL (standard deviation, 61.5841) with volixibat and 16.497 ng/mL (12.9150) with placebo. Total and low-density lipoprotein cholesterol levels decreased in the volixibat group, with median changes of - 0.70 mmol/L (range - 2.8 to 0.4) and - 0.6990 mmol/L (- 3.341 to 0.570), respectively.

CONCLUSIONS:

This study indicates that maximal inhibition of bile acid reabsorption, as assessed by FBA excretion, occurs at volixibat doses of ≥20 mg/day in obese and overweight adults, without appreciable change in gastrointestinal tolerability. These findings guided dose selection for an ongoing phase 2 study in patients with non-alcoholic steatohepatitis.

TRIAL REGISTRATION:

ClinicalTrials.gov identifier: NCT02287779 (registration first received 6 November 2014).

129

News (Medical) associated with Volixibat potassium ethanolate hydrate

19 Nov 2024

·endpts.com

GSK plots regulatory filings for PBC itch after positive Phase 3 readout

GSK’s linerixibat helped reduce itch in patients with an autoimmune liver disease that affects the bile ducts, meeting its primary endpoint in a late-stage trial. If approved, linerixibat would be the first drug on the US market to treat itch related to primary biliary cholangitis, a condition that mainly affects women and can cause liver damage. It’s also associated with a relentless itch that feels like it’s under the skin. While first-line primary biliary cholangitis treatment may control the disease, it may not reduce the severity of itching, also known as pruritus. “Patients describe it as bugs crawling, and they want to dig it out,” Megan McLaughlin, GSK’s medicine development leader for linerixibat, told Endpoints News. Linerixibat helped reduce patients’ monthly itch score over 24 weeks compared to placebo in the Phase 3 GLISTEN trial, GSK announced Tuesday at the American Association for the Study of Liver Diseases conference. GSK didn’t have any hard data to share, as the trial remains ongoing. But the latest readout gives the company “all the data we need for the primary analysis, which is what we’ve agreed with global regulators to submit,” McLaughlin said. The company is planning regulatory submissions in the US and EU in the first half of 2025. Linerixibat is an ileal bile acid transporter (IBAT). It works by inhibiting the reuptake of bile acids, which is thought to be a root cause of itch in PBC patients. GSK estimates that 510,000 patients globally will have PBC by 2030, and just under half of those patients will experience a severe enough itch to require specific treatment. The drug could compete with Mirum’s rival IBAT inhibitor volixibat, which read out positive Phase 2b data in PBC in June. McLaughlin said linerixibat could have an advantage by getting to market first. “The itch associated with PBC for many patients is unrelenting and often severe but is a symptom that is frequently overlooked or dismissed,” Carol Roberts, president of a patient support group called The PBCers Organization, said in GSK’s news release. “It has a significant impact on quality of life and mental health for people with PBC.” Editor’s Note: This story has been updated to clarify the definition of PBC, and that there is one first-line option for PBC patients.

Phase 2Clinical ResultPhase 3

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

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 Volixibat potassium ethanolate hydrate

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Primary Biliary Cholangitis	Phase 2	US	Mirum Pharmaceuticals, Inc.	22 Sep 2021
Primary Biliary Cholangitis	Phase 2	BE	Mirum Pharmaceuticals, Inc.	22 Sep 2021
Primary Biliary Cholangitis	Phase 2	FR	Mirum Pharmaceuticals, Inc.	22 Sep 2021
Primary Biliary Cholangitis	Phase 2	DE	Mirum Pharmaceuticals, Inc.	22 Sep 2021
Primary Biliary Cholangitis	Phase 2	IL	Mirum Pharmaceuticals, Inc.	22 Sep 2021
Primary Biliary Cholangitis	Phase 2	IT	Mirum Pharmaceuticals, Inc.	22 Sep 2021
Primary Biliary Cholangitis	Phase 2	NL	Mirum Pharmaceuticals, Inc.	22 Sep 2021
Primary Biliary Cholangitis	Phase 2	ES	Mirum Pharmaceuticals, Inc.	22 Sep 2021
Primary Biliary Cholangitis	Phase 2	GB	Mirum Pharmaceuticals, Inc.	22 Sep 2021
Intrahepatic Cholestasis of Pregnancy	Phase 2	US	Mirum Pharmaceuticals, Inc.	04 Jan 2021

Clinical Result

Indication

Phase

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04718961 (OHANA, CTgov)	Phase 2	Intrahepatic Cholestasis of Pregnancy	4	Placebo	mnjxqcacut(auoekjwrhz) = omrsqyfbcm kbmmncexgh (mhbcfdglnd, bkrctbtrdj - xtpwzpmtrx) View more	-	06 Aug 2024
VANTAGE (Biospace) Manual	Phase 2	Primary Biliary Cholangitis	30	volixibat	ezvrurukmr(kfpaozxuwu) = cehkyfrpxl sxdasfduox (bsukmtanhe, 0.414) View more	Positive	17 Jun 2024
				volixibat (20mg)	ezvrurukmr(kfpaozxuwu) = guiwkhluvu sxdasfduox (bsukmtanhe, 0.609)
NCT04718961 (OHANA, AASLD2023) Manual	Phase 2	Intrahepatic Cholestasis of Pregnancy	4	Volixibat	lfqekyegxz(slyvzpwkhd) = inebdjwtyu gcmqakegkh (dxjphgqrop ) View more	Positive	13 Nov 2023
NCT02787304 (Pubmed \| J Hepatol) Manual	Phase 2	Nonalcoholic Steatohepatitis	197	volixibat	ujuikjdrcn(cuhxilwigw) = ubexnvhqil qxpohfhpoo (txfmwlfacs ) View more	Negative	01 Aug 2020
				Placebo	ujuikjdrcn(cuhxilwigw) = dtbjyzcghy qxpohfhpoo (txfmwlfacs )
NCT02787304 (CTgov)	Phase 2	Nonalcoholic Steatohepatitis	197	SHP626 (SHP626 5 Milligram (mg))	dszyyaochf(ltkasbzdep) = htuqpswlel hfiaxejafn (yvqxnelbav, ixvorwhiga - ooxatnkdlw) View more	-	25 Nov 2019
				SHP626 (SHP626 10 Milligram (mg))	dszyyaochf(ltkasbzdep) = krjicdamtk hfiaxejafn (yvqxnelbav, qtrbfdclrl - xveneamanc) View more
NCT02287779 (Pubmed \| BMC Pharmacol Toxicol) Manual	Phase 1	Nonalcoholic Steatohepatitis	84	volixibat	ptrmxqznjt(hizjxxpiuy) = no serious adverse events itlspenlhw (pekqvfdvts )	Positive	16 Mar 2018
				Placebo
NCT02571192 (Pubmed \| Eur J Drug Metab Pharmacokinet) Manual	Phase 1	-	8	[ 14 C]-Volixibat	ysshlgaoxv(yykntbangk) = No radioactivity was observed in plasma or whole blood. The percentage (mean ± standard deviation) of total radioactivity in urine was 0.01 ± 0.007%. The vast majority (92.3 ± 5.25%) of volixibat was recovered in feces (69.2 ± 33.1% within 24 h). tpjyihgceg (fxhdqxozov ) View more	Positive	01 Feb 2018
NASH_TAG2017	Not Applicable	Nonalcoholic Steatohepatitis	-	Volixibat	pdwsmlsjio(naozuozhlw) = The frequency of bowel movements increased from an overall median of 1 daily evacuation pre-dose to 2 evacuations during treatment kyjpnxorqp (mhjiiezhgt ) View more	-	05 Jan 2017
				Placebo
NCT02287779 (CTgov)	Phase 1	Nonalcoholic Steatohepatitis \| Obesity	84	Placebo	xhcwqtjyrq(kwimniiayo) = ufdvrktfyl umsfoytgjc (phjmqjzjjv, ilnfyqqjox - iwkiupaehv) View more	-	07 Dec 2016

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