Programs

Mirum is developing transformative medicines for rare cholestatic liver diseases, including Alagille syndrome (ALGS)progressive familial intrahepatic cholestasis (PFIC)biliary atresia (BA)primary sclerosing cholangitis (PSC) and intrahepatic cholestasis of pregnancy (ICP), and primary biliary cholangitis.

We’re committed to creating life-changing medicines for children like Cedar.

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How ASBT Inhibition Works

Cholestasis is characterized by impaired flow of bile, resulting in accumulation of toxic levels of bile acids in the liver. This leads to liver injury, progressive liver disease and, if left untreated, can result in fibrosis, cirrhosis, liver failure and death. Patients with cholestatic liver disease typically experience debilitating itching (pruritus), which dramatically impacts quality of life and can lead to scarring, sleep deprivation, significant fatigue and psycho-social effects.

Mirum’s therapies are selective inhibitors of the apical sodium-dependent bile acid transporter (ASBT). ASBT is present in the small intestine and mediates the uptake of bile acids in the intestines, recycling them back to the liver. ASBT inhibition results in more bile acids being excreted in the feces, leading to lower levels of bile acids systemically, thereby reducing bile acid mediated liver damage. This leads to improvements in liver function, pruritus and other symptoms of cholestatic liver diseases.

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Redirects bile acid flow by inhibiting reuptake by ASBT

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Interrupts recirculation of bile acids to the liver

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Increases fecal bile acid excretion

Pipeline

ProgramDiseaseStatus
MaralixibatAlagille Syndrome (ALGS)Initiated rolling NDA submission
Launched Expanded Access Program
MaralixibatProgressive Familial Intrahepatic Cholestasis (PFIC)MAA filing for PFIC2 in Europe – 4Q20
MaralixibatBiliary Atresia (BA)IND clearance received
ODD received in Europe
VolixibatIntrahepatic Cholestasis of Pregnancy (ICP)Planning Clinical Program
VolixibatPrimary Sclerosing Cholangitis (PSC)IND clearance received

Program

Disease

Development Stage

Preclinical

Phase 1

Randomized Studies

Filing

Milestones

Filing

Expanded access program launched

Status

PDUFA Sep. 29, 2021

Filing

MAA in Europe

Randomized Studies

MARCH Phase 3

Status

EU launch planned for Q1 2022

MARCH topline data early 2022

Randomized Studies

EMBARK study enrolling

Status

Study initiated in Q1 2021

Randomized Studies

VISTAS study enrolling

Status

Study initiated in Q1 2021

Randomized Study

OHANA study enrolling

Status

Study initiated in Q1 2021

Randomized Study

Status

Study initiation 2H 2021

Program

Gene Therapy Programs**

Disease

VTX-803

Preclinical

Status

ODD designation in U.S. and Europe

Program

Gene Therapy Programs**

Disease

VTX-802

Preclinical

*Proposed indication: Cholestatic pruritus associated with ALGS

**VTX-803 and VTX-802 are proprietary gene therapy programs under development by Vivet Therapeutics. Mirum has option to in-license up to IND.

Maralixibat’s safety profile has been well validated, having been evaluated in more than 1,600 patients, including more than 120 children.

Maralixibat

Maralixibat is a novel, minimally absorbed, orally administered investigational medication being evaluated in several rare cholestatic liver diseases. Maralixibat inhibits the apical sodium-dependent bile acid transporter (ASBT), resulting in more bile acids being excreted in the feces, leading to lower levels of bile acids systemically, thereby potentially reducing bile acid-mediated liver damage and related effects and complications. Maralixibat has data spanning more than six years of clinical evaluation in patients with Alagille syndrome (ALGS) and progressive familial intrahepatic cholestasis (PFIC).

In the ICONIC Phase 2b ALGS clinical trial, patients receiving maralixibat experienced significant reductions in bile acids and pruritus compared to placebo, as well as improvements in quality of life,  xanthomas and accelerated growth long-term.

In the Phase 2 INDIGO study for PFIC, patients with PFIC2 (a genetically defined subset of PFIC also known as bile salt export pump deficiency), who achieved serum bile acid control during a five-year analysis were shown to have significant improvement in transplant-free survival. Patients who responded to maralixibat also experienced improvements across multiple parameters including normalization of liver enzyme and bilirubin levels, decreased pruritus, and improvements in growth.

The most frequent treatment-related adverse events were diarrhea and abdominal pain.

Until maralixibat is approved and available for prescribing, the medication can be provided to eligible patients with ALGS through Mirum’s expanded access program (EAP). For more information, please visit ALGSEAP.com. To learn more about the Phase 3 MARCH PFIC clinical trial, visit the study website at PFICtrial.com. For more information about the Phase 2 EMBARK study, visit clinicaltrials.gov.

The U.S. Food and Drug Administration has granted maralixibat Breakthrough Therapy designation for the treatment of pruritus associated with ALGS one year of age and older and for the treatment of PFIC2. Orphan Drug Designation was also granted to maralixibat for the treatment of patients with PFIC, ALGS and biliary atresia in the United States.

Volixibat

Volixibat is an oral, minimally absorbed agent designed to selectively inhibit the apical sodium dependent bile acid transporter (ASBT). Volixibat may offer a novel approach in the treatment of adult cholestatic diseases by blocking the recycling of bile acids through inhibition of ASBT, thereby reducing bile acids systemically and in the liver. Phase 1 and Phase 2 studies of volixibat demonstrated on-target increased fecal bile acid excretion, a pharmacodynamic marker of ASBT inhibition. Volixibat has been evaluated in more than 400 individuals across multiple clinical trials.

We have initiated several clinical studies to evaluate volixibat’s potential in several cholestatic diseases, including:

  • Phase 2b OHANA study for patients with intrahepatic cholestasis of pregnancy (currently enrolling),
  • Phase 2b VISTAS study for patients with primary sclerosing cholangitis (currently enrolling),
  • Phase 2 study for patients with primary biliary cholangitis (study initiation planned for the second half of 2021)

Publications &
Presentations

Pediatric cholestasis: Itching for an alternative to liver transplantation

Mirum-sponsored symposium – WCPGHAN 2021

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An important intestinal transporter that regulates the enterohepatic circulation of bile acids and cholesterol homeostasis: The apical sodium-dependent bile acid transporter (SLC10A2/ASBT)

Xiao, L & Pan, G, Clinics and Research in Hepatology and Gastroenterology (2017) 41, 509—515

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Role of the Intestinal Bile Acid Transporters in Bile Acid and Drug Disposition

Dawson, PA, Handb Exp Pharmacol. 2011;(201):169-203

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