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BATTLE BILE ACID BUILDUP WITH LIVMARLI*

Help relieve
cholestatic pruritus.

*LIVMARLI, an ileal bile acid transporter (IBAT) inhibitor, interrupts recirculation of bile acids to the liver, increasing fecal excretion and reducing bile acid levels in the body. The complete mechanism by which LIVMARLI improves cholestatic pruritus in patients with Alagille syndrome is unknown.1-3

*LIVMARLI, an ileal bile acid transporter (IBAT) inhibitor, interrupts recirculation of bile acids to the liver, increasing fecal excretion and reducing bile acid levels in the body. The complete mechanism by which LIVMARLI improves cholestatic pruritus in patients with Alagille syndrome is unknown.1-3

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OUTMATCH THE SCRATCH!

Cholestatic Pruritus Efficacy

LIVMARLI Provides Significant Improvements in Cholestatic Pruritus3

Significant improvements in cholestatic pruritus from baseline were achieved as early as Week 3 and maintained through 1 year in patients with Alagille syndrome taking once-daily LIVMARLI (P<0.0001).3,4

For patients who remained on treatment with LIVMARLI in the open-label extension (n=15), cholestatic pruritus responses compared with baseline were durable through nearly 4 years.3

IMPROVEMENTS IN CHOLESTATIC PRURITUS OVER TIME3,4
Improvements in cholestatic pruritus over time graph Improvements in cholestatic pruritus over time graph
View Study Design and Select Baseline Characteristics
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LIVER LEAGUE STUDY HALL

Study Design

ICONIC is the first and only pivotal study of an IBAT* inhibitor in Alagille syndrome to demonstrate significant improvement in cholestatic pruritus1†

The ICONIC study assessed efficacy and safety of treatment with LIVMARLI in children ≥1 year old with cholestatic pruritus associated with Alagille syndrome.1,2

This study consisted of an 18-week open-label treatment period; a 4-week randomized, double-blind, placebo-controlled drug-withdrawal period; a subsequent 26-week open-label treatment period; and a long-term open-label extension period.1,2

Cholestatic pruritus responses to LIVMARLI were assessed through approximately 4 years.1

SELECT BASELINE CHARACTERISTICS1

All Participants (N=31)
Mean age at baseline visit, years (SD)5.4 (4.2)
Sex, n (%)—
Female12 (39)
Male19 (61)
Genotyped mutation within JAG1, n (%)31 (100)
History of receiving treatment for pruritus, n (%)—
Any medication29 (94)
Ursodeoxycholic acid25 (81)
Rifampicin23 (74)
Naltrexone1 (3)
Sertraline1 (3)
Trial parameter, mean (SD)—
ItchRO(Obs) weekly morning 
average severity score‖		2.9 (0.5)
CSS score3.3 (0.9)
sBA, µmol/L283 (211)

*IBAT=ileal bile acid transporter.

†Mean difference –1.4 points [95% CI, –2.1, –0.8].1

‡Included a 6-week dose escalation period for all participants during the first 6 weeks of the open-label treatment period and for participants who received placebo during the RWD.

§Twice per day dosing was allowed after Week 100. The approved dosage of LIVMARLI is 380 mcg/kg once daily.

‖Average ItchRO(Obs) scores are based on the 7 days prior to baseline visit.

FSV supplements were available as SOC throughout the study. No changes beyond SOC in supplementation occurred during the study.1

Safety, tolerability, and pharmacokinetics of LIVMARLI in patients aged 3 months to 1 year were evaluated in RISE, a 13-week, open-label, phase 2 study (N=8). Participants received LIVMARLI 380 μg/kg once daily, in addition to standard of care.2,3

CSS=Clinician Scratch Scale; FSV=fat-soluble vitamin; ItchRO=Itch Reported Outcome; JAG1=jagged canonical Notch ligand 1; RWD=randomized withdrawal period; sBA=serum bile acid; SD=standard deviation; SOC=standard of care.

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. LIVMARLI® (maralixibat) oral solution. Prescribing Information. Mirum Pharmaceuticals, Inc. 3. Gonzales E, Jankowska I, Horslen S, et al. Safety and tolerability characterization of maralixibat in infants with ALGS from 2 months of age: interim results from the RISE study. Poster presented at: American Association for the Study of Liver Diseases: The Liver Meeting; November 4-8, 2022; Washington, DC.

Pie chart displaying the percentage of patients who experienced clinically meaningful improvements in cholestatic pruritus compared with baseline

During the first year of treatment, 84% (n=26/31) of patients with Alagille syndrome experienced clinically meaningful improvements in cholestatic pruritus compared with baseline with once-daily LIVMARLI.3

  • “Clinically meaningful” was defined as ≥1-point ItchRO(Obs) improvement vs baseline (caregiver-reported pruritus score)3

At 1 year, improvements in cholestatic pruritus were correlated with decreases in serum bile acid (sBA) (r=0.47).5

POST HOC ANALYSIS:

During the first year, patients receiving LIVMARLI in the pivotal ICONIC trial had an increasing proportion of days with minimal to no itch.6

  • In patients who remained on LIVMARLI (n=21) during the open-label extension (beyond 48 weeks), the median proportion of days with minimal to no itch was 95%6§

*Cholestatic pruritus was assessed each day, in the morning and evening, using the Itch Reported Outcome (ItchRO) scale—a validated tool designed to assess the impact of itching in children with cholestatic liver disease, including Alagille syndrome. The ItchRO score is a 0–4 scale, where 0 is none, 1 is mild, 2 is moderate, 3 is severe, and 4 is very severe. Changes in ItchRO score of 1.0 or more have been shown to be clinically meaningful. ItchRO(Obs) was completed by caregivers and was the basis for the key pruritus endpoint. The patient-rated ItchRO (ItchRO[Pt]) was completed independently by participants aged 9 years or older and with caregiver assistance for participants aged 5–8 years.3

†Change from baseline, P<0.0001.

‡Included an initial 6-week dose escalation for participants previously receiving placebo.

§Based on mean daily morning ItchRO(Obs) scores in patients who remained on LIVMARLI through 4 years.

Always
Safety First!

LIVMARLI has a well-characterized safety and tolerability profile for cholestatic pruritus in patients with Alagille syndrome.1,7

See the Safety Profile

Encourage patients to download the Itch✓ app to help them track symptom patterns over time and generate customized reports to share at appointments.

Check Out the Itch✓ App

Mirum Access Plus assists both you and your patients at every turn, helping you navigate the payer approval process—and beyond—with ease.

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Mirum Access Plus

References: 1. LIVMARLI® (maralixibat) oral solution. Prescribing Information. Mirum Pharmaceuticals, Inc. 2. Martin P, Apostol G, Smith W, Jennings L, Vig P. Dose-dependent fecal bile acid excretion with apical sodium-dependent bile acid transporter inhibitors maralixibat and volixibat in a dose-ranging phase 1 study in overweight and obese adults. Poster presented at: American Association for the Study of Liver Diseases: The Liver Meeting; November 8-12, 2019; Boston, MA. 3. 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 4. 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. 5. Gonzales E, Vig P, Tucker E, et al. Pruritus intensity is associated with cholestasis biomarkers and quality of life measures after maralixibat treatment in children with Alagille syndrome. Poster presented at: American Association for the Study of Liver Diseases: The Liver Meeting Digital Experience™ (TLMdX); November 13-16, 2020. 6. Data on file. REF-00100. Mirum Pharmaceuticals, Inc. 7. Raman RK, Garner W, Vig P, Tucker E. An integrated analysis of long-term clinical safety in maralixibat-treated participants with Alagille syndrome. Poster presented at: European Association for the Study of the Liver (EASL): International Liver Congress; June 23-26, 2021.

Indication

LIVMARLI is indicated for the treatment of cholestatic pruritus in patients with Alagille syndrome (ALGS) 3 months of age and older.

Important Safety Information

Warnings and Precautions

Liver Test Abnormalities: Patients enrolled in clinical trials had abnormal liver tests at baseline. In the main clinical trial, treatment-emergent elevations or worsening of liver tests (ALT, AST or T/DB) relative to baseline were observed. Obtain baseline liver tests and monitor during treatment. 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. Discontinue permanently if a patient progresses to portal hypertension or experiences a hepatic decompensation event.

GI Adverse Reactions: Diarrhea, abdominal pain and vomiting were reported as the most common adverse reactions. If diarrhea, abdominal pain and/or vomiting occur and no other etiologies are found, consider reducing the dose or interrupting LIVMARLI. For diarrhea or vomiting, monitor for dehydration and treat promptly. Consider interrupting LIVMARLI dosing if a patient experiences persistent diarrhea or has diarrhea with accompanying signs and symptoms such as bloody stool, vomiting, dehydration requiring treatment, or fever. Restart LIVMARLI at 190 mcg/kg/day when diarrhea, abdominal pain or vomiting resolve, and increase the dose as tolerated. If they recur upon re-challenge, consider stopping LIVMARLI treatment.

Fat-Soluble Vitamin Deficiency: ALGS patients can have fat-soluble vitamin (FSV) deficiency (vitamins A, D, E, and K) at baseline, and LIVMARLI may affect absorption of FSV. In the main clinical trial, treatment emergent FSV deficiency was reported in 3 (10%) patients during 48 weeks of treatment. Obtain baseline serum levels and monitor during treatment, along with any clinical manifestations. Supplement if deficiency is observed. Consider discontinuing LIVMARLI if FSV deficiency persists or worsens despite adequate FSV supplementation.

Adverse Reactions

The most common adverse reactions (≥5%) are diarrhea, abdominal pain, vomiting, fat-soluble vitamin deficiency, liver test abnormalities, gastrointestinal bleeding and bone fractures.

Drug Interactions

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

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

LIVMARLI should be taken 30 minutes before a meal in the morning. The provided oral dosing dispenser must be used to accurately measure the dose. Any remaining LIVMARLI should be discarded 100 days after first opening the bottle.

Please see full Prescribing Information for LIVMARLI.

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References: 1. LIVMARLI® (maralixibat) oral solution. Prescribing Information. Mirum Pharmaceuticals, Inc. 2. Martin P, Apostol G, Smith W, Jennings L, Vig P. Dose-dependent fecal bile acid excretion with apical sodium-dependent bile acid transporter inhibitors maralixibat and volixibat in a dose-ranging phase 1 study in overweight and obese adults. Poster presented at: American Association for the Study of Liver Diseases: The Liver Meeting; November 8-12, 2019; Boston, MA. 3. 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 4. 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. 5. Gonzales E, Vig P, Tucker E, et al. Pruritus intensity is associated with cholestasis biomarkers and quality of life measures after maralixibat treatment in children with Alagille syndrome. Poster presented at: American Association for the Study of Liver Diseases: The Liver Meeting Digital Experience™ (TLMdX); November 13-16, 2020. 6. Data on file. REF-00100. Mirum Pharmaceuticals, Inc. 7. Raman RK, Garner W, Vig P, Tucker E. An integrated analysis of long-term clinical safety in maralixibat-treated participants with Alagille syndrome. Poster presented at: European Association for the Study of the Liver (EASL): International Liver Congress; June 23-26, 2021.

Indication

LIVMARLI is indicated for the treatment of cholestatic pruritus in patients with Alagille syndrome (ALGS) 3 months of age and older.

Important Safety Information

Warnings and Precautions

Liver Test Abnormalities: Patients enrolled in clinical trials had abnormal liver tests at baseline. In the main clinical trial, treatment-emergent elevations or worsening of liver tests (ALT, AST or T/DB) relative to baseline were observed. Obtain baseline liver tests and monitor during treatment. 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. Discontinue permanently if a patient progresses to portal hypertension or experiences a hepatic decompensation event.

GI Adverse Reactions: Diarrhea, abdominal pain and vomiting were reported as the most common adverse reactions. If diarrhea, abdominal pain and/or vomiting occur and no other etiologies are found, consider reducing the dose or interrupting LIVMARLI. For diarrhea or vomiting, monitor for dehydration and treat promptly. Consider interrupting LIVMARLI dosing if a patient experiences persistent diarrhea or has diarrhea with accompanying signs and symptoms such as bloody stool, vomiting, dehydration requiring treatment, or fever. Restart LIVMARLI at 190 mcg/kg/day when diarrhea, abdominal pain or vomiting resolve, and increase the dose as tolerated. If they recur upon re-challenge, consider stopping LIVMARLI treatment.

Fat-Soluble Vitamin Deficiency: ALGS patients can have fat-soluble vitamin (FSV) deficiency (vitamins A, D, E, and K) at baseline, and LIVMARLI may affect absorption of FSV. In the main clinical trial, treatment emergent FSV deficiency was reported in 3 (10%) patients during 48 weeks of treatment. Obtain baseline serum levels and monitor during treatment, along with any clinical manifestations. Supplement if deficiency is observed. Consider discontinuing LIVMARLI if FSV deficiency persists or worsens despite adequate FSV supplementation.

Adverse Reactions

The most common adverse reactions (≥5%) are diarrhea, abdominal pain, vomiting, fat-soluble vitamin deficiency, liver test abnormalities, gastrointestinal bleeding and bone fractures.

Drug Interactions

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

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

LIVMARLI should be taken 30 minutes before a meal in the morning. The provided oral dosing dispenser must be used to accurately measure the dose. Any remaining LIVMARLI should be discarded 100 days after first opening the bottle.

Please see full Prescribing Information for LIVMARLI.