A Remarkable

Turning Point

Impacting the lives 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

LIVMARLI®
(maralixibat) Oral Solution

Alagille Syndrome
(ALGS)

 Approved 1

LIVMARLI®
(maralixibat) Oral Solution

Progressive Familial Intrahepatic
Cholestasis (PFIC)

 Approved 2

LIVMARLI®
(maralixibat) Oral Solution

Cholestatic Pruritus (Additional Settings)

 EXPAND

CHENODAL®
(chenodiol)

Cerebrotendinous
xanthomatosis (CTX)

 RESTORE 3

Cholbam®
(cholic acid) capsules

Bile Acid Synthesis
Disorders and PBD-ZSD 4

 FDA Approved

VOLIXIBAT

Primary Sclerosing
Cholangitis (PSC)

 VISTAS 5

VOLIXIBAT

Primary Biliary
Cholangitis (PBC)

 VANTAGE 6

MRM-3379

Fragile X Syndrome

1 Approved in the below regions:

  •    U.S. – In cholestatic pruritus in patients with ALGS three months of age and older
  •    E.U. – In cholestatic pruritus in patients with ALGS two months of age and older
  •    Canada – In cholestatic prutitus 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.

2 Approved in the below regions:

  •    U.S. – In cholestatic pruritus in patients with PFIC 12 months of age and older
  •    E.U. – For the treatment of PFIC in patients three months of age and older

 

3 Chenodal (CDCA) is not indicated for CTX but has received a medical necessity determination in the U.S. by the FDA for CTX. Data from the Phase 3 RESTORE clinical trial examining the safety and efficacy of Chenodal for the treatment of CTX was announced on October 2, 2023.

 

4 PBD-ZSD = Peroxisome biogensis disorder-Zellweger Spectrum Disorder

 

5 Blinded Interim analysis for VISTAS study in PSC announced on June 17, 2024; study continues as planned 

 

6 Interim data from the Phase 2b VANTAGE clinical trial examining the safety and efficacy of volixibat for the treatment of PBC was announced on June 17, 2024

LIVMARLI®
(maralixibat) Oral Solution

Alagille Syndrome
(ALGS)

Phase
Approved
Approved 1

LIVMARLI®
(maralixibat) Oral Solution

Progressive Familial Intrahepatic
Cholestasis (PFIC)

Phase
Phase 2b/Phase 3
Approved 2

LIVMARLI®
(maralixibat) Oral Solution

Cholestatic Pruritus (Additional Settings)

Phase
EXPAND

CHENODAL®
(chenodiol)

Cerebrotendinous
xanthomatosis (CTX)

Phase
Phase 2b/Phase 3
RESTORE 3

Cholbam®
(cholic acid) capsules

Bile Acid Synthesis
Disorders and PBD-ZSD 4

Phase
FDA Approved

VOLIXIBAT

Primary Sclerosing
Cholangitis (PSC)

Phase
Phase 2b/Phase 3
VISTAS 5

VOLIXIBAT

Primary Biliary
Cholangitis (PBC)

Phase
Phase 2b/Phase 3
VANTAGE 6

MRM-3379

Fragile X Syndrome

Phase

1 Approved in the below regions:

  •    U.S. – In cholestatic pruritus in patients with ALGS three months of age and older
  •    E.U. – In cholestatic pruritus in patients with ALGS two months of age and older
  •    Canada – In cholestatic prutitus 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.

2 Approved in the below regions:

  •    U.S. – In cholestatic pruritus in patients with PFIC 12 months of age and older
  •    E.U. – For the treatment of PFIC in patients three months of age and older

 

3 Chenodal (CDCA) is not indicated for CTX but has received a medical necessity determination in the U.S. by the FDA for CTX. Data from the Phase 3 RESTORE clinical trial examining the safety and efficacy of Chenodal for the treatment of CTX was announced on October 2, 2023.

 

4 PBD-ZSD = Peroxisome biogensis disorder-Zellweger Spectrum Disorder

 

5 Blinded Interim analysis for VISTAS study in PSC announced on June 17, 2024; study continues as planned 

 

6 Interim data from the Phase 2b VANTAGE clinical trial examining the safety and efficacy of volixibat for the treatment of PBC was announced on June 17, 2024

Learn more about our investigational therapies

LIVMARLI® (maralixibat)

About LIVMARLI (maralixibat)

LIVMARLI (maralixibat) is an oral, minimally-absorbed, ileal bile acid transporter (IBAT) inhibitor.1 It was investigated as a treatment for rare liver diseases including Alagille syndrome (ALGS) and Progressive Familial Intrahepatic Cholestasis (PFIC). LIVMARLI is currently being evaluated for pruritus in rare cholestatic settings in the Phase 3 EXPAND study.

LIVMARLI is approved by the FDA for the treatment of cholestatic pruritus in patients with ALGS three months of age and older, and for the treatment of cholestatic pruritus in patients with PFIC 12 months of age and older.


LIVMARLI is not for use in patients with PFIC type 2 who have a severe defect in the bile salt export pump (BSEP) protein.

LIVMARLI has been authorized by the European Commission for the treatment of cholestatic pruritus in patients with ALGS two months of age and older, and for the treatment of PFIC in patients three months of age and older.

LIVMARLI (maralixibat oral solution) has been authorized by Health Canada for the treatment of 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.

    • LIVMARLI has also been granted Breakthrough Therapy designation for the treatment of PFIC2.2 Lastly, Orphan Drug Designation was granted to LIVMARLI 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 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.

    LIVMARLI (maralixibat) safety profile

    What are the possible side effects of LIVMARLI?
    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.

    • Liver injury. Changes in certain liver tests are common in patients with Alagille syndrome and PFIC but may worsen during treatment. These changes may be a sign of liver injury. In PFIC, this can be serious or may lead to transplant or death. Your health care provider should do blood tests and physical exams before starting and during treatment to check your liver function. Tell your health care provider right away if you get any signs or symptoms of liver problems, including:
      • nausea or vomiting

      • your skin or the white part of your eye turns yellow

      • dark or brown urine

      • pain on the right side of your stomach (abdomen)

      • fullness, bloating, or fluid in your stomach area (ascites)

      • loss of appetite

      • bleeding or bruising more easily than normal, including vomiting blood

    • Stomach and intestinal (gastrointestinal) problems. LIVMARLI can cause stomach and intestinal problems, including diarrhea and stomach pain. Diarrhea can also cause the loss of too much body fluid (severe dehydration). Your health care provider may advise you to monitor for new or worsening stomach problems, including stomach pain, diarrhea, blood in your stool, or vomiting Tell your health care provider right away if you have any new or worsening signs or symptoms of stomach and intestinal problems, including:
      • diarrhea

      • more frequent bowel movements than usual

      • stools that are black, tarry, or sticky, or have blood or mucous

      • severe stomach-area pain or tenderness

      • vomiting

      • urinating less often than usual

      • dizziness

      • headache

    • 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 health care provider should do blood tests before starting and during treatment, and may monitor for bone fractures and bleeding, which are common side effects.


    Tell your health care provider about all medicines that you take, as LIVMARLI may interact with other medicines. If you take a medicine that lowers cholesterol by binding bile acids, such as cholestyramine, colesevelam, or colestipol, take it at least 4 hours before or 4 hours after you take LIVMARLI.

    Your health care provider may change your dose, or temporarily or permanently stop treatment if you have certain side effects.

    These are not all of the possible side effects of LIVMARLI. For more information, ask your health care provider or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

    In patients with Alagille syndrome, LIVMARLI is taken by mouth, 1 time each day, 30 minutes before a meal in the morning. In patients with PFIC, LIVMARLI is taken by mouth, 2 times each day, 30 minutes before a meal. Be sure to use the provided oral dosing dispenser to accurately measure the dose of medicine.

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

Interim results from the VANTAGE study evaluating volixibat in patients with PBC demonstrated statistically significant (-3.82, p<0.0001) improvement in pruritus for volixibat and a placebo-adjusted difference of -2.32 points, 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 one case resulting in discontinuation. There were no clinically meaningful changes in liver biomarkers.


The blinded interim analysis for the VISTAS study in PSC was announced on June 17, 2024. The study is continuing to enroll.


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

MRM-3379

About MRM-3379

MRM-3379 is a phosphodiesterase-4D (PDE4D) allosteric inhibitor that we believe may offer a novel approach in the treatment of Fragile X syndrome (FXS) by blocking PDE4D, thereby restoring transcription of genes involved in synaptic plasticity to improve cognition, language, and daily function. MRM-3379 is being studied in FXS.

Mode of Action

MRM-3379 is an allosteric inhibitor of PDE4D that interacts with upstream conserved regions (UCR) domain of select PDE4D splice variants to close the catalytic site and thereby, increase cAMP signaling to promote plasticity via AMPA receptor insertion, cytoskeletal rearrangement, and activation of gene expression.

What we’ve seen in clinical trials

Data from Phase 1 clinical studies of MRM-3379 in more than 120 people were generally well- tolerated with most adverse effects of mild intensity and transient.

Our clinical
trials

At Mirum, working together with the rare 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)

Pruritus in Rare Cholestatic Settings
Phase 3 EXPAND Study — Enrolling

Evaluating the safety and efficacy of LIVMARLI (maralixibat) in pediatric and adult patients with pruritus associated with general cholestatic liver disease.

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 expand access to safe, effective therapies.

LIVMARLI Expanded Access Program for ALGS and PFIC

Mirum has a limited Early/Expanded Access Program (EAP) open in some countries outside of the US, offering access to LIVMARLI® (maralixibat) for eligible patients with Alagille syndrome (ALGS) and progressive familial intrahepatic cholestasis (PFIC) who do not have access to LIVMARLI and do not qualify for ongoing clinical trials, until LIVMARLI® is commercially available in those countries.


Compassionate Use

Currently, we are prioritizing access to LIVMARLI and our investigational products through our clinical trials. We are not able to offer compassionate use access to LIVMARLI or our investigational products at this time.

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

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.

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