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

93%

of patients with ALGS treated with LIVMARLI who were pruritus responders (>1-point reduction in ItchRO[Obs] at Week 48) remained transplant free at 6 years^2,3

Long-term liver impact^2,3

In a post hoc analysis, patients with ALGS who were treated with LIVMARLI in 3 long-term clinical studies (N=76) were followed to identify predictors of long-term, transplant-free survival.*^†

A graph of long-term liver impact and transplant-free survival.

Cholestatic pruritus response, defined as a reduction in ItchRO >1 point, was identified as a predictor of long-term, transplant-free survival.

*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.²

The MERGE study assessed the long-term durability of response to LIVMARLI in 86 patients enrolled from several clinical studies⁵

Patients who continued on LIVMARLI saw reductions in cholestatic pruritus and improvements in serum bile acid (sBA) levels up to

7years⁵

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7years⁵

Responses over time⁵

A table of the response to LIVMARLI over time.

Liver function tests over 7 years⁵

Total and direct bilirubin over time

While LIVMARLI treatment is associated with a potential for DILI, significant (P<0.05) reductions in total and direct bilirubin were observed in some patients who continued on LIVMARLI long term.^1,5

ALT and AST over time

No meaningful changes in ALT or AST were observed.

Changes in growth (height and weight)⁵

Results from the MERGE study show that patients who saw a reduction in cholestatic pruritus were also more likely to grow and gain weight over time.

Changes in height from start of treatment^†

A graph of long-term changes in height and weight from start of treatment.

Patients also gained weight within the first year of treatment with LIVMARLI. Improvements in both height and weight continued through 7 years.^‡

ALT=alanine aminotransferase; AST=aspartate aminotransferase; BL=baseline; DILI=drug-induced liver injury; ItchRO=Itch Reported Outcome; ItchRO(Obs)=Itch Reported Outcome for Observer.

*All data are median (Q1, Q3) and are observed values.⁵
^†Changes in height and weight were measured against the average patient Z-score at the start of treatment (average Z-score: –1.6).
^‡A total of 23 patients remained on treatment at year 7.

ICONIC study

In the ICONIC study, patients treated with LIVMARLI experienced a reduction in cholestatic pruritus, with mean ItchRO(Obs) scores decreasing from 3.1 (0.5) at BL to 1.4 (0.9) at Week 18. Patients who continued LIVMARLI for 22 weeks maintained their cholestatic pruritus reduction, while those who stopped LIVMARLI after Week 18 and switched to placebo returned to BL scores by Week 22. After resuming LIVMARLI in the open-label treatment phase, both groups had similar mean scores by Week 28. These ItchRO(Obs) findings were consistent with patient-reported cholestatic pruritus severity in those aged 5 and older¹
In IMAGO (280 µg/kg/daily) and its extension study, IMAGINE, and in ITCH (280 µg/kg/daily) and its extension study, IMAGINE-II, responses were durable for up to ~1.5 years^5,6*
In prior studies, improvements in sBA levels were observed in some patients with ALGS who were taking LIVMARLI⁵

References:

1. LIVMARLI® (maralixibat). Prescribing Information. Mirum Pharmaceuticals, Inc. 2. 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 3. Data on file. REF-00342. Mirum Pharmaceuticals, Inc. 4. Sokol J, Gonzales E, Kamath BM, et al. Predictors of 6-year event-free survival in patients with Alagille syndrome treated with maralixibat, an IBAT inhibitor. Paper presented at: European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN): Annual Meeting; June 22-25, 2022; Copenhagen, Denmark. 5. 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. Presented at: North American Society for Pediatric Gastroenterology, Hepatology and Nutrition Annual Meeting (NASPGHAN): November 6-9, 2024; Hollywood, Florida. 6. Shneider BL, Brown MB, Haber B, et al. A multicenter study of the outcome of biliary atresia in the United States, 1997 to 2000. J Pediatr. 2006;148(4):467-474. doi:10.1016/j.jpeds.2005.12.054

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.

Additional data in Alagille syndrome (ALGS)