Response Rates | LIVMARLI® (maralixibat) oral solution and tablets

Broad data available across both indications in LIVMARLI responders

*Cholestatic pruritus was assessed in the pivotal ICONIC study in patients ≥1 year old with ALGS and in the Phase 3 MARCH-PFIC study in patients ≥12 months to <18 years old with PFIC.^1,7
^†Based on a post hoc analysis. The impact of LIVMARLI treatment on transplant-free survival has not been established. No liver histology to assess hepatic fibrosis was collected. Transplant-free survival was defined as time to liver transplant or death.⁵
^‡Bilirubin levels were assessed in patients with PFIC in an exploratory analysis of the MARCH-PFIC and MARCH-ON studies.⁹
^§Growth in patients with PFIC was observed in an exploratory analysis of the MARCH-PFIC and MARCH-ON studies.¹⁰

References:

1. Gonzales E, Hardikar W, Stormon M, et al. Efficacy and safety of maralixibat treatment in patients with Alagille syndrome and cholestatic pruritus (ICONIC): a randomised phase 2 study. Lancet. 2021;398(10311):1581-1592. doi:10.1016/S0140-6736(21)01256-3 2. Gonzales E, Sturm E, Stormon E, et al. Durability of treatment effect with long-term maralixibat in children with Alagille syndrome: 4-year safety and efficacy. Presented at: American Association for the Study of Liver Diseases Annual Meeting: The Liver Meeting; November 8-12, 2019; Boston, MA. 3. Data on file. REF-00106. Mirum Pharmaceuticals, Inc. 4. Murray KF, Kamath BM, Gonzalès E, et al. Clinical benefits of maralixibat for patients with Alagille syndrome are durable through 7 years of treatment: data from the MERGE study. Poster presented at: North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Annual Meeting (NASPGHAN): November 6-9, 2024; Hollywood, Florida. 5. Sokol RJ, Gonzales EM, Kamath BM, et al. Predictors of 6-year event-free survival in Alagille syndrome patients treated with maralixibat, an ileal bile acid transporter inhibitor. Hepatology. 2023;78(6):1698-1710. doi:10.1097/HEP.0000000000000502 6. Data on file. REF-00342. Mirum Pharmaceuticals, Inc. 7. LIVMARLI® (maralixibat). Prescribing Information. Mirum Pharmaceuticals, Inc. 8. Miethke AG, Moukarzel A, Porta G, et al. Maralixibat in progressive familial intrahepatic cholestasis (MARCH-PFIC): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Gastroenterol Hepatol. 2024;9(7):620-631. doi:10.1016/S2468-1253(24)00080-3 9. Data on file. REF-01712. Mirum Pharmaceuticals, Inc. 10. Miethke A, Moukarzel A, Porta G, et al. Long-term maintenance of response and improved liver health with maralixibat in patients with progressive familial intrahepatic cholestasis (PFIC): data from the MARCH-ON Study. Presented at: American Association for the Study of Liver Diseases (AASLD) The Liver Meeting: November 10-14, 2023; Boston, MA.

Indications

LIVMARLI (maralixibat) oral solution and tablets are indicated for the treatment of cholestatic pruritus in patients who are 3 months of age and older with Alagille syndrome.

LIVMARLI (maralixibat) oral solution and tablets are indicated for the treatment of cholestatic pruritus in patients who are 12 months of age and older with progressive familial intrahepatic cholestasis (PFIC).

Limitations of Use: LIVMARLI is not recommended in a subgroup of PFIC type 2 patients with specific ABCB11 variants resulting in nonfunctional or complete absence of bile salt export pump (BSEP) protein.

Important Safety Information

CONTRAINDICATIONS

LIVMARLI (maralixibat) oral solution and tablets are contraindicated in patients with prior or active hepatic decompensation events (eg, variceal hemorrhage, ascites, or hepatic encephalopathy).

WARNINGS AND PRECAUTIONS

Hepatotoxicity: LIVMARLI treatment is associated with a potential for drug-induced liver injury (DILI). In the PFIC trial, treatment-emergent hepatic decompensation events and elevations of liver tests or worsening of liver tests occurred. Two patients experienced DILI attributable to LIVMARLI. Two additional patients experienced DILI in the open-label extension portion of the trial. Of these 4 patients, 1 patient required liver transplant and another patient died.

In the Alagille syndrome trial, treatment-emergent elevations of liver tests or worsening of liver tests occurred.

Obtain baseline liver tests and monitor during treatment. Liver-related adverse reactions and physical signs of hepatic decompensation should also be monitored. Dose reduction or treatment interruption may be considered if abnormalities occur in the absence of other causes. For persistent or recurrent liver test abnormalities, consider treatment discontinuation. Permanently discontinue LIVMARLI if a patient experiences the following: persistent or recurrent liver test abnormalities, clinical hepatitis, or a hepatic decompensation event.

Gastrointestinal Adverse Reactions: Diarrhea and abdominal pain were reported as the most common adverse reactions. Monitor for dehydration and treat promptly. Consider reducing the dosage or interrupting LIVMARLI treatment if a patient experiences persistent diarrhea or diarrhea with bloody stool, vomiting, dehydration requiring treatment, or fever.

Fat-Soluble Vitamin (FSV) Deficiency: Patients can have FSV deficiency (vitamins A, D, E, and K) at baseline, and LIVMARLI may adversely affect absorption of FSVs. Treatment-emergent bone fracture events have been observed more frequently with patients treated with LIVMARLI compared with patients treated with placebo. If bone fractures or bleeding occurs, consider interrupting LIVMARLI and supplement with FSVs. LIVMARLI can be restarted once FSV deficiency is corrected and maintained at corrected levels.

Risk of Propylene Glycol Toxicity (Pediatric Patients Less Than 5 Years of Age): LIVMARLI oral solution contains propylene glycol. Total daily intake of propylene glycol should be considered for managing the risk of propylene glycol toxicity. Monitor patients for signs of propylene glycol toxicity. Discontinue LIVMARLI if toxicity is suspected.

ADVERSE REACTIONS

Alagille syndrome: The most common adverse reactions are diarrhea, abdominal pain, vomiting, FSV deficiency, liver test abnormalities, and bone fractures.

PFIC: The most common adverse reactions are diarrhea, FSV deficiency, abdominal pain, liver test abnormalities, hematochezia, and bone fractures.

DRUG INTERACTIONS

Administer LIVMARLI at least 4 hours before or 4 hours after administration of bile acid binding resins.

A decrease in the absorption of OATP2B1 substrates (eg, statins) due to OATP2B1 inhibition by LIVMARLI in the GI tract cannot be ruled out. Consider monitoring the drug effects of OATP2B1 substrates as needed.

DOSING INFORMATION

In patients with Alagille syndrome, LIVMARLI is taken once daily, 30 minutes before a meal in the morning. In patients with PFIC, LIVMARLI is taken twice daily, 30 minutes before a meal. Refer to the dosing by weight guidelines in the full Prescribing Information for complete details on dosing for the oral solution and tablet formulations. The provided oral solution dosing dispenser must be used to accurately measure the dose. Any remaining LIVMARLI oral solution should be discarded 100 days after first opening the bottle. LIVMARLI tablets can be used in patients weighing ≥25 kg who can swallow tablets.

Please see full Prescribing Information for LIVMARLI.

Broad responder data