Programs

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

1
2
3
4
5
6
7

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.

1
2
3
1

Redirects bile acid flow by inhibiting reuptake by ASBT

2

Interrupts recirculation of bile acids to the liver

3

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

Phase 1

Phase 2

Phase 3

Filed

Approved

Additional Information

Phase 2

Rolling NDA initiated based on Phase 2 data

Status

Initiated rolling NDA submission Launched EAP

Phase 3

Status

MAA filing for PFIC2 in Europe – 4Q20

Phase 2

Status

IND clearance received ODD received in Europe

Phase 1

Status

Planned Clinical Program

Phase 1

Status

IND clearance received

NDA: New Drug Application; EAP: Expanded Access Program; MAA: Marketing Authorization Application; IND: Investigational New Drug;  ODD: Orphan Drug Designation

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 drug 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. More than 1,600 individuals have received maralixibat, including more than 120 children who have received maralixibat as an investigational treatment for Alagille syndrome (ALGS) and progressive familial intrahepatic cholestasis (PFIC).

In the ICONIC Phase 2b ALGS clinical trial, patients taking maralixibat had significant reductions in bile acids and pruritus compared to placebo, as well as reduction in xanthomas and accelerated growth long-term.

In a Phase 2 PFIC study, a genetically defined subset of bile acid salt export pump (BSEP) deficient (PFIC2), patients responded to maralixibat.

The FDA has granted maralixibat Breakthrough Therapy designation for treatment of pruritus associated with ALGS in patients one year of age and older and for PFIC2. Maralixibat was generally well-tolerated throughout the studies. The most frequent treatment-related adverse events were diarrhea, abdominal pain, and vomiting. Until maralixibat is approved by the FDA and available for prescribing, the medication is available to patients with ALGS through Mirum’s expanded access program. For more information, please visit ALGSEAP.com. For more information about the Phase 3 study for maralixibat in pediatric patients with PFIC, visit PFICtrial.com.

Volixibat

Volixibat is an oral, minimally-absorbed investigational therapy designed to selectively inhibit ASBT, 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 adult cholestatic diseases by blocking recycling of bile acids, thereby reducing bile acids systemically. Data from Phase 1 and Phase 2 clinical trials of volixibat demonstrated decreases in LDL cholesterol, increases in C4 and increases in fecal bile acid content, all markers of ASBT inhibition. We plan to initiate Phase 2 clinical trials in primary sclerosing cholangitis (PSC) and intrahepatic cholestasis of pregnancy (ICP).

Publications &
Presentations

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

View Publication

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

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

View Publication

© 2020 – Mirum Pharmaceuticals