Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication LIVMARLI is an ileal bile acid transporter (IBAT) inhibitor indicated for: • the treatment of cholestatic pruritus in patients 3 months of age and older with Alagille syndrome (ALGS). ( 1.1 ) • the treatment of cholestatic pruritus in patients 12 months of age and older with progressive familial intrahepatic cholestasis (PFIC). FDA label
Also known as Livmarli Oral Product, Livmarli
Maralixibat · 7 trials · 7 indications
ItchRO(Obs) severity score = Itch Reported Outcome Observer assessment severity score; scale between 0 (not itchy at all) and 4 (extremely itchy); the lower the score the better.
The Score on the ItchRo scale is a score on a 5-point scale from 0 (no itch) to 4 (very severe itch)
The primary efficacy endpoint is the mean change in the average morning ItchRO(Obs) severity score between baseline and Weeks 15-26, using 4-week average morning ItchRO(Obs) severity scores (Mixed Model Repeated Measures). The baseline average morning ItchRO(Obs) severity score is defined as the 4-week average morning ItchRO(Obs) severity score prior to the first dose of the study medication. ItchRo(Obs) Severity Score = Itch Reported Outcome Observer assessment severity score; scale between 0 (not itchy at all) and 4 (extremely itchy); the lower the score the better.
TEAEs = Treatment-emergent Adverse Events
TEAE = Treatment-emergent Adverse Event; AESI = Adverse Event of Special Interest..
| Arm | Type | Description |
|---|---|---|
| Maralixibat | EXPERIMENTAL | Participants will receive maralixibat oral solution 300 μg/kg orally once daily for 1 week and then twice daily for 39 weeks. |
| Placebo | PLACEBO_COMPARATOR | Participants will receive placebo matched to maralixibat oral solution orally once daily for 1 week and then twice daily for 19 weeks. After 20 weeks, participants will receive maralixibat oral solution 300 μg/kg orally once daily for 1 week and then twice daily for 19 weeks. |
| Maralixibat Treatment | EXPERIMENTAL | Participants will receive maralixibat tablets or oral solution. |
| Double Blind - Maralixibat | EXPERIMENTAL | The double-blind period comprised of 4-8 weeks of dose escalation followed by 18 - 22 weeks of stable dosing treatment, after which participants were transferred to the open-label arm. |
| Double Blind - Placebo | PLACEBO_COMPARATOR | The double-blind period comprised of 4-8 weeks of dose escalation followed by 18 - 22 weeks of stable dosing treatment, after which participants were transferred to the open-label arm. |
| Open Label - Maralixibat | EXPERIMENTAL | The Open-Label period comprised of 4-8 weeks of dose escalation followed by 70 - 74 weeks of stable dosing treatment. During the OLE, all participants, regardless of treatment assignment in the double-blind period, received maralixibat. |
| Name | Type | Description |
|---|---|---|
| Maralixibat | DRUG | Maralixibat will be provided as an oral solution along with 0.5-, 1.0-, and 3.0-mL sized dosing dispensers. During the double-blind dose escalation period (4 weeks), the study drug (maralixibat) will be administered once daily for 1 week and then twice daily (BID; morning and evening). During the double-blind stable dosing period (16 weeks), participants will be treated with 300 μg/kg BID or the maximum tolerated dose (determined during the double-blind dose-escalation period) of maralixibat. During the open-label dose escalation period (4 weeks), all participants will receive maralixibat treatment once daily for 1 week and then twice daily (BID; morning and evening). During the open-label stable dosing period (at least 16 weeks), participants will be treated with 300 μg/kg BID or the maximum tolerated dose (determined during the open-label dose-escalation period) of maralixibat. |
| Placebo | OTHER | Placebo matched to maralixibat will be provided as an oral solution along with 0.5-, 1.0-, and 3.0-mL sized dosing dispensers. During the double-blind dose escalation period (4 weeks), study drug will be administered once daily for 1 week and then twice daily (BID; morning and evening). During the double-blind stable dosing period (16 weeks), participants will be treated with 300 μg/kg BID or the maximum tolerated dose (determined during the double-blind dose-escalation period) of study drug. During the open-label dose escalation period (4 weeks), all participants will receive maralixibat treatment once daily for 1 week and then twice daily (BID; morning and evening). During the open-label stable dosing period (16 weeks), participants will be treated with 300 μg/kg BID or the maximum tolerated dose (determined during the open-label dose-escalation period) of maralixibat. |
Inclusion Criteria: 1. Informed consent and assent (as applicable) 2. Age ≥6 months at time of baseline visit 3. Diagnosis of a rare cholestatic liver disease with cholestatic pruritus based on the following: 1. Chronic liver biochemical abnormalities (\>90 days) and/or pathological evidence of...
Maralixibat is an investigational small molecule developed by Mirum Pharmaceuticals, Inc. (ticker MIRM). It is being studied in cholestatic liver diseases, including biliary atresia, cholestatic liver disease, intrahepatic cholestasis of pregnancy, and progressive familial intrahepatic cholestasis. It is administered as an oral therapy and remains in clinical development.
Maralixibat targets SLC10A2, also known as the apical sodium-dependent bile acid transporter (ASBT). It acts as an inhibitor of this transporter, which is involved in bile acid reabsorption in the ileum. By inhibiting SLC10A2, maralixibat is designed to reduce bile acid levels and associated cholestatic pruritus.
Maralixibat is being evaluated for pruritus associated with cholestatic liver disease, excluding Alagille syndrome, PFIC, primary biliary cholangitis, and primary sclerosing cholangitis. It is also under study in biliary atresia, intrahepatic cholestasis of pregnancy, and progressive familial intrahepatic cholestasis. These uses are investigational and not yet established.
Maralixibat is developed by Mirum Pharmaceuticals, Inc., a biopharmaceutical company that trades under the ticker symbol MIRM. Mirum is responsible for the clinical development program across the cholestatic liver disease indications being studied.
Maralixibat is in Phase 2 clinical development for several cholestatic liver disease indications, with a Phase 3 trial also underway. It is investigational and has not been established as approved for the indications described here. Development spans biliary atresia, cholestatic liver disease, intrahepatic cholestasis of pregnancy, and progressive familial intrahepatic cholestasis.
Maralixibat has been studied in several trials, including NCT07823127 in intrahepatic cholestasis of pregnancy, NCT06553768 in pruritus associated with general cholestatic liver disease, NCT04729751 in infant cholestatic liver diseases including PFIC and Alagille syndrome, and NCT04524390 in biliary atresia post-Kasai. These trials include placebo-controlled and open-label designs.