Common adverse reactions

A table listing adverse reactions in the MARCH-PFIC clinical study.

ALT=alanine transaminase; AST=aspartate aminotransferase; PFIC=progressive familial intrahepatic cholestasis.
*Abdominal pain includes abdominal pain, abdominal pain upper, and abdominal distension; transaminases increased includes hypertransaminasemia, ALT abnormal, ALT increased, AST abnormal, AST increased, transaminases increased, and hepatic enzyme increased; bone fractures include upper limb fracture, lower limb fracture, radius fracture, ulna fracture, femur fracture, and foot fracture.

Additional
safety

Most gastrointestinal side effects were transient and the majority resolved in <1 week.²

Diarrhea was the most frequent adverse reaction; the majority of episodes were mild and transient. Diarrhea resolved, on average, within 5.5 days.^1,3

One patient with an event of mild diarrhea discontinued treatment
Treatment interruptions or dose reductions occurred in 3 patients due to diarrhea or abdominal pain

Treatment with LIVMARLI is associated with a potential for drug-induced liver injury.¹

Treatment-emergent elevations of liver tests or worsening of liver tests, relative to baseline values, and hepatic decompensation events were observed
Two patients experienced drug-induced liver injury (DILI) attributable to LIVMARLI. One patient received 570 mcg/kg twice daily and the second patient required dose interruption and reduction
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. The contribution of LIVMARLI in these 2 cases is uncertain
In the placebo-controlled arm of the trial, 2 patients treated with LIVMARLI developed cholangitis or cholecystitis within 3 weeks of drug discontinuation. Four patients treated with LIVMARLI developed cholecystitis or cholangitis in the open-label extension
Treatment-emergent bone fracture events were observed. Three patients treated with LIVMARLI experienced bone fractures compared with none with placebo. Two patients treated with LIVMARLI developed bone fractures in the open-label extension
Patients receiving LIVMARLI reported more frequent treatment-emergent events of hematochezia (4 [8.5%] vs 1 [2.2%]) and a decrease in hemoglobin ≥2 g/dL from baseline (8 [17%] vs 1 [2.2%]) compared with patients receiving placebo

Patients with PFIC can have fat-soluble vitamin (FSV) deficiency (vitamins A, D, E, and/or K) at baseline.¹

LIVMARLI may affect absorption of FSV
In patients with PFIC, treatment-emergent FSV deficiency was reported in 13 (28%) patients treated with LIVMARLI vs 16 (35%) patients treated with placebo during 26 weeks of treatment

References:

1. LIVMARLI® (maralixibat). Prescribing Information. Mirum Pharmaceuticals, Inc. 2. Gonzalez-Peralta R, Miethke AG, Moukarzel A, et al. Analysis of safety in maralixibat-treated participants with progressive familial intrahepatic cholestasis: data from the MARCH trial. Poster presented at: North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) Annual Meeting: October 4-7, 2023; San Diego, California. 3. Miethke A, Moukarzel A, Porta G, et al. Efficacy and safety of maralixibat in patients with progressive familial intrahepatic cholestasis (MARCH-PFIC): a randomized placebo-controlled phase 3 study. Presented at: North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) Annual Meeting: October 4-7, 2023; San Diego, CA. 4. 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.

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.

Grounded by a well-characterized safety and tolerability profile