A Remarkable

Turning Point

Impacting the livers of those with rare disease is more than a mission-it’s our calling. At Mirum, our work is in service of closing treatment gaps to open a world of possibilities for patients and their families.

Patients and families play a crucial role in our clinical trial designs and approaches. We work with them to help identify what matters most as our investigational treatments are evaluated. This includes the development of surveys, pruritus (itch) severity scales, and e-diaries that help create a better understanding of the burdens of rare diseases.

Development pipeline

LIVMARLI® (maralixibat)
Oral Solution 		Preclinical Phase 1 Phase 2b/Phase 3 Approved
Alagille Syndrome
(ALGS)		 FDA Approved* EC-Authorized** Health Canada Approved***
Progressive
Familial Intrahepatic
Cholestasis (PFIC)		 MARCH
Biliary Atresia (BA) EMBARK
VOLIXIBAT
Primary Sclerosing
Cholangitis (PSC)		 VISTAS
Primary Biliary
Cholangitis (PBC)		 VANTAGE
CHENODAL®
(chenodiol)
Cerebrotendinous
xanthomatosis (CTX)		 RESTORE****

* In cholestatic pruritus in patients with ALGS three months of age and older
** In cholestatic pruritus in patients with ALGS two months of age and older
*** In cholestatic pruritus in patients with ALGS

  • Pediatrics (12 months to 18 years): Based on the data submitted and reviewed by Health Canada, the safety and efficacy of LIVMARLI in these pediatric patients have been established. Therefore, Health Canada has authorized an indication for pediatric use.
  • Pediatrics (<12 months): The safety and efficacy of LIVMARLI in these pediatric patients have not been established.

****Chenodal (CDCA) is not indicated for CTX but has received a medical necessity determination in the U.S. by the FDA for CTX. The Phase 3 RESTORE clinical trial is currently underway to examine the safety and efficacy of Chenodal® (CDCA) for the treatment of CTX.

Topline data for Phase 3 MARCH study announced on October 24, 2022.

LIVMARLI® (maralixibat)
Oral Solution
Alagille Syndrome (ALGS)
Phase
FDA Approved* APPROVED
EC Approved**
Health Canada Approved***
LIVMARLI® (maralixibat)
Oral Solution
Progressive Familial Intrahepatic
Cholestasis (PFIC)
Phase
MARCH Phase 2b/Phase 3
LIVMARLI® (maralixibat)
Oral Solution
Biliary Atresia (BA)
Phase
EMBARK Phase 2b/Phase 3 APPROVED
VOLIXIBAT
Primary Sclerosing
Cholangitis (PSC)
Phase
VISTAS Phase 2b/Phase 3 APPROVED
VOLIXIBAT
Primary Biliary
Cholangitis (PBC)
Phase
VANTAGE Phase 2b/Phase 3 APPROVED
CHENODAL® (chenodiol)
Cerebrotendinous xanthomatosis (CTX)
Phase
RESTORE**** Phase 2b/Phase 3 APPROVED

* In cholestatic pruritus in patients with ALGS three months of age and older
** In cholestatic pruritus in patients with ALGS two months of age and older
*** In cholestatic pruritus in patients with ALGS

  • Pediatrics (12 months to 18 years): Based on the data submitted and reviewed by Health Canada, the safety and efficacy of LIVMARLI in these pediatric patients have been established. Therefore, Health Canada has authorized an indication for pediatric use.
  • Pediatrics (<12 months): The safety and efficacy of LIVMARLI in these pediatric patients have not been established.

****Chenodal (CDCA) is not indicated for CTX but has received a medical necessity determination in the U.S. by the FDA for CTX. The Phase 3 RESTORE clinical trial is currently underway to examine the safety and efficacy of Chenodal® (CDCA) for the treatment of CTX.

Topline data for Phase 3 MARCH study announced on October 24, 2022.

Learn more about our investigational therapies

LIVMARLI® (maralixibat)

About LIVMARLI (maralixibat)

LIVMARLI (maralixibat) is a novel, minimally absorbed, orally administered liquid.1 It’s an investigational medicine being evaluated as a treatment for rare liver diseases, including Alagille syndrome (ALGS), progressive familial intrahepatic cholestasis (PFIC) and biliary atresia (BA).

LIVMARLI (maralixibat) has been approved by the FDA for the treatment of cholestatic pruritus in patients with Alagille syndrome (ALGS) three months of age and older.

LIVMARLI (maralixibat) has been authorized by the European Commission for the treatment of cholestatic pruritus in patients with Alagille syndrome (ALGS) two months of age and older.

LIVMARLI (maralixibat oral solution) has been authorized by Health Canada for the treatment of cholestatic pruritus in patients with Alagille syndrome (ALGS).

  • Pediatrics (12 months to 18 years): Based on the data submitted and reviewed by Health Canada, the safety and efficacy of LIVMARLI in these pediatric patients have been established. Therefore, Health Canada has authorized an indication for pediatric use.
  • Pediatrics (<12 months): The safety and efficacy of LIVMARLI in these pediatric patients have not been established.

    • LIVMARLI (maralixibat) has also been granted Breakthrough Therapy designation for the treatment of PFIC2.2 Lastly, Orphan Drug Designation was granted to LIVMARLI (maralixibat) for the treatment of patients with PFIC and biliary atresia in the United States.3,4

    Connect with a physician to learn more about
    LIVMARLI (maralixibat) and discuss access:
    FOR U.S. PATIENTS: MIRUM ACCESS PLUS PROGRAM
    FOR PATIENTS OUTSIDE OF THE U.S.: MIRUM EXPANDED ACCESS PROGRAM

    Mode of action

    LIVMARLI (maralixibat) works by blocking an important bile acid transport protein on the surface of the small intestine. This results in more bile acids being excreted in the feces, which then leads to lower levels of bile acids systemically.1

    What we’ve seen in clinical studies in ALGS

    In the Phase 2 ICONIC study, children with ALGS taking LIVMARLI (maralixibat) saw significant reductions in itch (pruritus).1

    What we’ve seen in clinical studies in PFIC

    INDIGO was a Phase 2 open label study with more than 5 years of data. Patients with PFIC2 who achieved serum bile acid (sBA) response were shown to have promising results across an array of parameters.5

    In the MARCH Phase 3 study, LIVMARLI met its primary endpoint of improvement in pruritus severity (p=0.0098) with highly statistically significant effects observed across all PFIC subtypes studied. The study also showed significant improvements in other endpoints with total bilirubin and growth versus placebo at six months.

    Clinical trials in biliary atresia

    This Phase 2b EMBARK study evaluating LIVMARLI (maralixibat) in pediatric patients with biliary atresia was initiated in early 2021.

    LEARN MORE ABOUT OUR CLINICAL TRIALS
    LIVMARLI (maralixibat) safety profile

    LIVMARLI can cause serious side effects, including:

    Changes in liver tests: Changes in certain liver tests are common in patients with Alagille syndrome but may worsen during treatment with LIVMARLI. These changes may be a sign of liver injury and can be serious. Your health care provider should do blood tests before starting and during treatment to check your liver function. Stomach and intestinal (gastrointestinal) problems: LIVMARLI can cause stomach and intestinal problems, including diarrhea, stomach pain, and vomiting during treatment. Fat Soluble Vitamin Deficiency: This vitamin deficiency is common in patients with Alagille syndrome but may worsen during treatment.

Volixibat

About volixibat

Volixibat is a minimally absorbed, orally administered investigational therapy designed to selectively inhibit ileal bile acid transporter (IBAT), a protein that is primarily responsible for recycling bile acids from the intestine to the liver. We believe that volixibat may offer a novel approach in the treatment of rare liver diseases impacting both adults and children by blocking the recycling of bile acids, thereby reducing bile acids systemically. Volixibat is currently being studied in primary sclerosing cholangitis and primary biliary cholangitis.6

Mode of action

Volixibat works by blocking an important bile acid transport protein on the surface of the small intestine. This results in more bile acids being excreted in the feces. This leads to lower levels of bile acids systemically, thereby potentially reducing bile acid–mediated liver damage and its related effects and complications. Additionally, volixibat is designed to be minimally absorbed into the bloodstream.6

What we’ve seen in clinical trials

Data from Phase 1 and Phase 2 clinical trials of volixibat in more than 400 people demonstrated Increases in fecal bile acid excretion (a marker of IBAT inhibition), resulting in dose-related increase in 7αC4.6

Volixibat clinical trials

We are now evaluating volixibat’s potential in several cholestatic diseases including the Phase 2b VISTAS study for patients with primary sclerosing cholangitis (PSC) and the Phase 2b VANTAGE study for adults with primary biliary cholangitis (PBC).

LEARN MORE ABOUT OUR CLINICAL TRIALS

Chenodal® (chenodiol)

About Chenodal (chenodiol)

Chenodiol is another name for chenodeoxycholic acid (CDCA). CDCA is a naturally occurring bile acid that was approved in 1983 under the brand name Chenix for the treatment of people with radiolucent stones in the gallbladder. More recently, the US Food and Drug Administration (FDA) granted Chenodal (also CDCA) orphan drug designation for cerebrotendinous xanthomatosis (CTX). CTX is a rare progressive disorder that can affect the brain, spinal cord, tendons, eyes and arteries. Chenodal is not indicated for the treatment of CTX but has received a medical necessity determination in the US by the FDA. The Phase 3 RESTORE clinical trial is currently underway to examine the safety and efficacy of CDCA for the treatment of CTX.

Our Approach

Our investigational approach is to evaluate the use of CDCA as a direct replacement therapy option for the restoration of physiologic bile acids and the regulation of cholestanol and bile alcohols compared to placebo.

RESTORE Study

The RESTORE Study is a Phase 3 double-blind, placebo-controlled 24-week clinical trial, assessing the safety and efficacy of Chenodal in patients with CTX. The primary efficacy endpoint of the RESTORE Study is the change from baseline in urine bile alcohols at the end of each double-blind treatment period. The study protocol allows for rescue measures to protect patient safety. The RESTORE study may support greater identification and earlier treatment efforts in this ultra-rare progressive neurological disorder.

LEARN MORE ABOUT OUR CLINICAL TRIALS

Our clinical
trials

At Mirum, working together with the rare liver disease community is paramount.
Patients and their families play an integral role in helping us evaluate investigational
therapies through clinical trials and obtain the evidence we need for regulatory
approval in the U.S. and beyond.

For more information about Mirum’s clinical trials, please contact:

Clinical trials for LIVMARLI® (maralixibat)

Progressive Familial Intrahepatic Cholestasis (PFIC)
Phase 3 MARCH Study — Completed

Evaluating the efficacy and safety of LIVMARLI (maralixibat) in patients with PFIC.

View full study details on www.clinicaltrials.gov
PFIC and ALGS
PFIC and ALGS Progressive Familial Intrahepatic Cholestasis (PFIC) and Alagille syndrome (ALGS) Phase 2 RISE Study — Enrolling

Evaluating the safety and tolerability of LIVMARLI (maralixibat) in infants with PFIC or ALGS.

View full study details on WWW.CLINICALTRIALS.GOV

Expanded Access Program for Patients with PFIC and ALGS

Mirum’s Expanded Access Program offers access to LIVMARLI (maralixibat) for the treatment of eligible patients with cholestatic pruritus associated with ALGS, outside of the U.S., and for patients with PFIC, who do not have access to clinical trials.


  • Requests to participate must be made by a licensed physician
  • Interested physicians in Canada and the US who are interested in the ALGS EAP should contact:
    Mirumalgs@clinigengroup.com
  • Interested physicians in Canada and the US who are interested in the PFIC EAP should contact:
    MirumPFIC@clinigengroup.com
  • Interested physicians outside of Canada and the US who are interested in the PFIC or ALGS EAP should contact:
    medicineaccess@clinigengroup.COM

    Biliary Atresia (BA)
    Phase 2b EMBARK Study

    Evaluating the efficacy and safety of LIVMARLI (maralixibat) in infants with BA after Kasai procedure.

    View full study details on www.clinicaltrials.gov

Clinical trials for volixibat

Primary Sclerosing Cholangitis (PSC)
Phase 2b VISTAS Study — Enrolling

Evaluating efficacy and safety of volixibat in patients with itching caused by PSC.

View full study details on WWW.CLINICALTRIALS.GOV
Primary Biliary Cholangitis (PBC)
Phase 2b VANTAGE Study — Enrolling

Evaluating efficacy and safety of volixibat in patients with itching caused by PBC.

View full study details on WWW.CLINICALTRIALS.GOV

Clinical trial for Chenodal® (chenodiol)

Cerebrotendinous Xanthomatosis (CTX)
Phase 3 RESTORE Study

Evaluating the efficacy and safety of chenodeoxycholic acid in adult and pediatric patients with cerebrotendinous xanthomatosis.

View full study details on WWW.CLINICALTRIALS.GOV

Expanded Access/Compassionate Use

Clinical development is a critical part of evaluating experimental therapies as potential impactful medicines for people with rare liver diseases. We are committed to rigorous testing of experimental treatments in order to secure regulatory approval and enable the medicine to be available to as many patients as quickly as possible.

LIVMARLI Expanded Access Program for ALGS and PFIC

Mirum has an Expanded Access Program (EAP) open across multiple countries, offering access to LIVMARLI® (maralixibat) for eligible patients with Alagille syndrome (ALGS) and progressive familial intrahepatic cholestasis (PFIC) who do not have access to ongoing clinical trials.


LIVMARLI Compassionate Use

Mirum is committed to making accommodations so that patients who have exhausted other treatment options may, under specific conditions, have access to LIVMARLI.

Mirum will consider single patient compassionate use access to LIVMARLI, outside of a clinical trial, when all the following criteria are met:

  1. The patient has a serious or life-threatening condition.
  2. The patient has undergone standard treatments without success and there are no other suitable treatment options.
  3. The patient is not eligible for an ongoing clinical trial.
  4. The physician making the request is qualified to treat the patient and agrees to comply with local regulations.
  5. The physician determines the potential benefits of LIVMARLI outweigh the risks to the individual patient.

    For individual compassionate use requests beyond ALGS and PFIC, please contact:
    CompassionateUse@mirumpharma.com

    Mirum reserves the right to revise this policy at any time.

    Currently, we are not able to offer compassionate use access to the investigational product, volixibat.

References

  1. Gonzales E, Sturm E, Stormon E, et al. Durability of treatment effect with long-term maralixibat in children with Alagille syndrome. Oral presentation at: American Association for the Study of Liver Diseases Annual Meeting (The Liver Meeting); November 8-12, 2019; Boston, MA.
  2. Mirum Pharmaceuticals Announces Breakthrough Therapy Designation for Maralixibat for the Treatment of Pruritus Associated with Alagille Syndrome. Mirum Pharmaceuticals, Inc. Accessed June 2, 2021. https://ir.mirumpharma.com/news-releases/news-release-details/mirum-pharmaceuticals-announces-breakthrough-therapy-designation
  3. Mirum Pharmaceuticals Completes Successful Pre-NDA Meeting with FDA for Maralixibat. Mirum Pharmaceuticals, Inc. Accessed June 2, 2021.
  4. Mirum Pharmaceuticals Announces Completion of Rolling NDA Submission for Maralixibat in Alagille Syndrome. Mirum Pharmaceuticals, Inc. Accessed June 2, 2021. https://ir.mirumpharma.com/news-releases/news-release-details/mirum-pharmaceuticals-announces-completion-rolling-nda
  5. Thompson R. Serum bile acid control in long-term maralixibat-treated patients is associated with native liver survival in children with progressive familial intrahepatic cholestasis due to bile salt export pump deficiency. Presented at: EASL 2020; August 2020. Accessed April 29, 2021.
  6. Key CC, McKibben A, Chien E, et al. A Phase 1 dose-ranging study assessing fecal bile acid excretion by volixibat, an apical sodium‑dependent bile acid transporter inhibitor, and coadministration with loperamide.