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EFFICACY

Improvements in
Cholestatic Pruritus

Cholestatic Pruritus Efficacy

Meaningful Improvements in Cholestatic Pruritus Were Seen as Early as 2 Weeks and Sustained Through 2 Years1-3

LIVMARLI was studied in the broadest population of progressive familial intrahepatic cholestasis (PFIC) subtypes and was shown to provide statistically significant improvements in cholestatic pruritus vs placebo at 6 months. Improvements were seen as early as Week 2.1,2,4

BSEP cohort (Primary endpoint)2
Cholestatic pruritus score
(ItchRO[Obs])
BSEP ItchRO chart
Weekly average cholestatic pruritus score
(ItchRO[Obs]) over time
BSEP weekly average chart

BSEP=bile salt export pump; ItchRO(Obs)=Itch Reported Outcome (Observer).

See Study Design >
All-PFIC cohort (Secondary endpoint)1,2
Cholestatic pruritus score
(ItchRO[Obs])
All-PFIC itchRO chart
Weekly average cholestatic pruritus score
(ItchRO[Obs]) over time
All-PFIC weekly average chart
See Study Design >
Improvements during
the first 6 months
of treatment
64%

of patients in the All-PFIC cohort were considered cholestatic pruritus responders and experienced clinically meaningful improvements in cholestatic pruritus vs 29% of patients treated with placebo (P=0.0064).2

  • Cholestatic pruritus responders had a ≥1-point ItchRO(Obs) improvement or a score of ≤1.02
More days with little to
no cholestatic pruritus

Over the 6-month period, patients treated with LIVMARLI (n=33) had significantly more days with little to no cholestatic pruritus than those who received placebo (n=31) (62% vs 28%, least squares [LS] mean difference 0.34, P<0.0001)5

Improvements Sustained Through 2 Years

In patients who remained on LIVMARLI (n=13) during the open-label extension, statistically significant improvements in cholestatic pruritus from baseline were sustained through 2 years (P<0.001).3

Improvements in Serum Bile Acid Levels

50%

of patients treated with LIVMARLI in the All-PFIC cohort were considered serum bile acid (sBA) responders vs 7% of patients treated with placebo (P=0.0003).2

  • sBA responders were defined as patients who achieved a ≥75% reduction in sBA levels or sBA <102 µmol/L2
sBA responders2
≥75% reduction or sBA <102 µmol/L
sBA responders-chart

In the All-PFIC cohort, patients taking LIVMARLI saw statistically significant improvements in sBA levels compared with placebo (–157 µmol/L vs 3 µmol/L, LS mean difference –160 µmol/L, P<0.0001).2

Study Design

The Broadest Population of PFIC Subtypes Studied

The MARCH-PFIC study was a 26-week, Phase 3, randomized, placebo-controlled study that assessed efficacy and safety of treatment with LIVMARLI in patients 12 months to <18 years old with cholestatic pruritus in PFIC.1,2

View Study Design and Baseline Characteristics
Study design2,3
MARCH-PFIC study design
  • Cholestatic pruritus
  • sBA levels
  • Bilirubin
  • Growth Z-scores
  • Incidence of treatment-emergent adverse events
The study populations for MARCH-PFIC included2
Study population
Participants had the following baseline characteristics (full cohort)2
Baseline characteristics

Cholestatic pruritus was assessed at baseline using the Itch Reported Outcome (ItchRO) scale. ItchRO is a 0 to 4 scale, where 0 is none and 4 is very severe. This scale takes itch-related symptoms into consideration, including patients’ skin damage, sleep, and irritability.6,7

  • Participants’ baseline scores were calculated as the average of the daily ItchRO scores over the 2 consecutive weeks during the screening period7

ALT=alanine transaminase; BL=baseline; BSEP=bile salt export pump; DB=direct bilirubin; FIC1=familial intrahepatic cholestasis associated protein 1; LS=least squares; MMRM=mixed model for repeated measures; MDR3=multidrug resistance class III; MYO5B=myosin VB; nt=non-truncated mutations; t=truncated mutations; TB=total bilirubin; TJP2=tight junction protein 2.

*In the dose escalation period, the dose was increased weekly starting at 142.5 mcg/kg twice daily to a maximum dose of 570 mcg/kg twice daily.2

†Endpoints were analyzed using a repeated measures model (MMRM) considering data from all study visits.1,2

‡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.1

§The full study cohort included 8 patients with prior surgery to treat PFIC. Surgery participants had the following PFIC types: non-truncated BSEP (LIVMARLI: 3; placebo: 0), FIC1 (LIVMARLI: 2; placebo: 2), and TJP2 (LIVMARLI: 0; placebo: 1).2

MARCH-PFIC is the largest Phase 3 study conducted in children with PFIC. It included PFIC types that had not previously been studied.2,4

Always Safety First!

LIVMARLI has a well-characterized safety and tolerability profile for cholestatic pruritus in patients with PFIC.1,2

See the Safety Profile

Convenient
Dosing

LIVMARLI is a liquid medication that is administered twice daily orally, 30 minutes before a meal.1

Look Into
LIVMARLI Dosing

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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References: 1. LIVMARLI® (maralixibat) oral solution. Prescribing Information. Mirum Pharmaceuticals, Inc. 2. 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 3. 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): 2-year 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. 4. Data on file. REF-01126. Mirum Pharmaceuticals, Inc. 5. Ekong U, Miethke AG, Mogul DB, et al. Maralixibat leads to significant reductions in pruritus and improvements in sleep with progressive familial intrahepatic cholestasis: Data from the MARCH trial. Presented at: North American Society for Pediatric Gastroenterology Hepatology and Nutrition (NASPGHAN) Annual Meeting: October 4-7, 2023; San Diego, CA. 6. Kamath BM, Abetz-Webb L, Kennedy C, et al. Development of a novel tool to assess the impact of itching in pediatric cholestasis. Patient. 2018;11(1):69-82. doi:10.1007/s40271-017-0266-4 7. Kamath BM, Spino C, McLain R, et al. Unraveling the relationship between itching, scratch scales, and biomarkers in children with Alagille syndrome. Hepatol Commun. 2020;4(7):1012-1018. doi:10.1002/hep4.1522

INDICATION

LIVMARLI is indicated for the treatment of cholestatic pruritus in patients 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 is 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.

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. Permanently discontinue LIVMARLI if a patient experiences the following: persistent or recurrent liver test abnormalities, clinical hepatitis upon rechallenge, or a hepatic decompensation event.

Gastrointestinal (GI) 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 dosing 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 occur, 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): 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

The most common adverse reactions are diarrhea, FSV deficiency, abdominal pain, liver test abnormalities, hematochezia, 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 twice daily 30 minutes before a meal. 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.

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References: 1. LIVMARLI® (maralixibat) oral solution. Prescribing Information. Mirum Pharmaceuticals, Inc. 2. 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 3. 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): 2-year 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. 4. Data on file. REF-01126. Mirum Pharmaceuticals, Inc. 5. Ekong U, Miethke AG, Mogul DB, et al. Maralixibat leads to significant reductions in pruritus and improvements in sleep with progressive familial intrahepatic cholestasis: Data from the MARCH trial. Presented at: North American Society for Pediatric Gastroenterology Hepatology and Nutrition (NASPGHAN) Annual Meeting: October 4-7, 2023; San Diego, CA. 6. Kamath BM, Abetz-Webb L, Kennedy C, et al. Development of a novel tool to assess the impact of itching in pediatric cholestasis. Patient. 2018;11(1):69-82. doi:10.1007/s40271-017-0266-4 7. Kamath BM, Spino C, McLain R, et al. Unraveling the relationship between itching, scratch scales, and biomarkers in children with Alagille syndrome. Hepatol Commun. 2020;4(7):1012-1018. doi:10.1002/hep4.1522

INDICATION

LIVMARLI is indicated for the treatment of cholestatic pruritus in patients 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 is 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.

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. Permanently discontinue LIVMARLI if a patient experiences the following: persistent or recurrent liver test abnormalities, clinical hepatitis upon rechallenge, or a hepatic decompensation event.

Gastrointestinal (GI) 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 dosing 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 occur, 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): 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

The most common adverse reactions are diarrhea, FSV deficiency, abdominal pain, liver test abnormalities, hematochezia, 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 twice daily 30 minutes before a meal. 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.