Meet Finley | LIVMARLI® (maralixibat) oral solution and tablets | HCP

Finley experienced multiple symptoms for months before finally starting LIVMARLI

Video of Finley

[00:00:00]

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Dani: You have to be careful with it.

Jay: [chuckles]

Jackson: He's turning it by himself.

Dani: Good job. You got to do one at a time.

Jay: My name's Jay.

Dani: I'm Dani. We have 2 beautiful boys: Jackson, who's four, and Finley, who's one.

Jay: Jackson's just [00:00:30] a mover and a shaker. He's a ball of energy. He's just always on the move. He's creative. He's energetic.

Dani: Finley's personality is a lot more mellow. He really enjoys reading books together, listening to music, and he really likes to see how things work. Jackson's pregnancy, super easy, no complications, no NICU stay, no hospital stay. It was a really straightforward pregnancy. Not with [00:01:00] Fin, though. Not with Fin. We were very excited to add another little baby to our family. So we got pregnant with Fin, something that was supposed to be joyous, ended up turning into not that.

Jay: In that TWAIN work ultrasound where they look at all of the anatomy of the fetus, they couldn't see one of the chambers of his heart. That was just the start of what [00:01:30] was going on. We went back for another ultrasound because he was measuring small. He was measuring, at that time, in the 11th percentile. We went back, and he was measuring in the 9th percentile, and that's when they found what's called an echogenic bowel. We were referred to see a high-risk pregnancy doctor every couple of weeks.

Dani: Finley was born a month early, so he spent the first 2 weeks of his life in the NICU. His liver numbers were really high, but they weren't [00:02:00] super concerned yet. They were just waiting to see if those liver numbers started to track down. That's when we heard the term bronze baby syndrome. This is what they call when they knew that something was wrong with Finley's liver. There's this one particular photo of Jay and Finley. He was holding him up over his shoulder.

Jay: You can see the fear in that picture, and that's one that will forever stick out to me, is that moment [00:02:30] where it set in that, " Okay, we're not going home right away. When we do go home, it's not going to be what we thought it was. It's not going to be what it was like when we had Jackson."

Dani: We weren't out of the woods in this one. We knew at this time there was something wrong. He was still jaundiced. He wasn't gaining weight, and it was a very isolating experience. It was during COVID. I, of course, refused to leave my newborn son, so I spent [00:03:00] a lot of my time there.

Jay: It was a lot. It was hard. A lot to process.

Dani: They did a lot of different tests. They did echo outside, and that's when they discovered that he had pulmonary stenosis. They wanted to do a liver biopsy to rule out biliary atresia and really look at the bile ducts and see how they were growing. They [00:03:30] told us, "We don't really have an answer." That's when we really first heard of Alagille syndrome, and that might be something that Finley has.

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Dani: I'm supposed to protect him, and I feel like the mutation is my fault, even though logically I know it's not. It was a brand-new mutation. It doesn't run in either of our families. I couldn't do my job as a mother to make sure he was born healthy. That's why I do a lot of research into what Alagille syndrome is, what other families go through. [00:04:30]

Jay: Some of the symptoms that we were experiencing after diagnosis were the continued poor weight gain and being undersized, jaundiced levels in his skin. We were starting to see signs of him itching.

Dani: The itch was one of the bigger pieces in that early diagnosis that we missed then, but now we understand it. Because a lot of the signs that our doctor told us to look out for: the rubbing of the face on your shoulder if you're holding him up [00:05:00] here, rubbing of the feet or belly when they're trying to do tummy time, and then the scratching of the eyes or grabbing at the ears. All those are normal hunger cues, sleepy cues, and so really trying to figure out what's the difference between the two. Looking back at it now, we definitely see that most of the signs were itching and not necessarily related to typical newborn behavior.

Finley, in the evening, his itch would be pretty bad. [00:05:30] He was waking up every two to three hours, well before that six-hour mark that our doctor told us that hydroxyzine would last. The itch impacted Finley's life. That period of time was a blur from how exhausted we all were. Jackson slept through the night, so it didn't seem to disrupt him, but it did disrupt our lives, though, when we were awake, because Jackson wanted to play, and Finley was really tired. Mommy and Daddy were really tired. It was a pretty rough, [00:06:00] dark time.

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[background conversation]

Jay: Our doctor had introduced LIVMARLI as a possible option for Finley pretty early on. After diagnosis, they work with a number of families in the area that have kids with [00:06:30] Alagille, and they've just seen it really help with the itch in those children.

Dani: For me, why I wanted to get Finley on LIVMARLI was the itch. Seeing him wake him up in the middle of the night, seeing him try to play with Jackson and eat his food and do all those things, and just to see those little grabbing at the eyes, grabbing at the ankles and feet, just seeing how much itching was really impacting him.

Jay: Finley started on LIVMARLI shortly after his first birthday [00:07:00] when we had our follow-up with his GI doctor. Around that four-week mark, we were really happy to see that he was reaching for his legs and feet less than what we would see when he would itch, and just had more time to be Finley. It was really awesome.

Dani: Yes. It was nice to see him be able to focus on something else outside the itch. You want him to thrive, be a child who isn't impacted by the itch through liver disease. You just want him to be a normal one-year-old child. Our doctors shared that there [00:07:30] could be some side effects for Finley after taking LIVMARLI, but we didn't really see any of those. We didn't see the diarrhea, no vomiting. We didn't really see any—

Jay: Changes in his vitamin levels, all remained stable.

Dani: None of the things that our doctors did share that we could potentially see on LIVMARLI, we didn't experience anything like that.

Jay: I think we've really tried to just see [00:08:00] how much has changed in the time he's been on it with the itch subsiding and going down, that it's just made doing these things more enjoyable for him. We get to celebrate those moments and look at how much fun he's having without seeing him grabbing at his knees, grabbing at his ears like we used to see. It's hard to quantify, but you just see him being a kid and having fun with his brother and doing the slide and playing at the park. It just warms your heart. It makes me happy. It makes us smile.

Dani: Just because [00:08:30] he has been dealt a certain hand in life, that doesn't mean his rare disease defines him. Finley is smart. He's happy, and he's healthy, or stable in his own way.

Jay: The ultimate goal would be for people to just understand that Finley is just like any other kid and that he may have some differences that make him look a little smaller or look a little different, but he's still capable of doing what anybody else [00:09:00] is. We want to be a voice for Finley and other kids with Alagille. We want people to understand.

Dani: I feel like you might not use the word fortunate a lot in the rare disease world, but we are really fortunate to have Alagille Alliance. Not too many rare diseases have this group of folks together that help provide the scientific research, help give you information, and connect with other families who are also going through Alagille with you. We feel very fortunate that we're part of such a [00:09:30] well-known and—

Jay: Tight community, too.

Dani: Yes.

Voice-Over:

INDICATION

LIVMARLI (maralixibat) oral solution and tablets are a prescription medicine used to treat cholestatic pruritus (itch) in patients who are 3 months of age and older with Alagille syndrome.

It is not known if LIVMARLI is safe and effective in children with Alagille syndrome who are under 3 months of age. It is not known if LIVMARLI is safe and effective [00:10:00] in adults who are 65 years of age and older.

IMPORTANT SAFETY INFORMATION

What are the possible side effects of LIVMARLI (maralixibat) oral solution and tablets? LIVMARLI can cause serious side effects, including:

Liver injury. Changes in certain liver tests are common in patients but may worsen during treatment with LIVMARLI. These changes may be a sign of liver injury and can be serious. Your health care provider should do blood tests and physical exams before starting and during treatment to check your liver function. [00:10:30] Tell your health care provider right away if you get any signs or symptoms of liver problems, including:
- nausea or vomiting
- your skin or the white part of your eye turns yellow
- dark or brown urine
- pain on the right side of your stomach (abdomen)
- fullness, bloating, or fluid in your stomach area (ascites)
- loss of appetite
- bleeding or bruising more easily than normal, including vomiting blood
Stomach and intestinal (gastrointestinal) problems. LIVMARLI can cause stomach and intestinal problems, including diarrhea and stomach pain during treatment. Diarrhea can also cause the loss of too much body fluid (severe dehydration).Your health care provider may advise you to [00:07:00] monitor for new or worsening stomach problems, including stomach pain, diarrhea, blood in your stool, or vomiting. Tell your health care provider right away if you have any new or worsening signs or symptoms of stomach and intestinal problems, including:
- diarrhea
- more frequent bowel movements than usual
- stools that are black, tarry, or sticky, or have blood [00:11:30] or mucous
- severe stomach-area pain or tenderness
- vomiting
- urinating less often than usual
- dizziness
- headache
A condition called Fat-Soluble Vitamin (FSV) Deficiency caused by low levels of certain vitamins (vitamin A, D, E, and K) stored in body fat. FSV deficiency is common in patients with Alagille syndrome but may worsen during treatment. Your health care provider should do blood tests before starting and during treatment, and may monitor for bone fractures and bleeding, [00:12:00] which are common side effects.

Tell your health care provider about all medicines that you take, as LIVMARLI may interact with other medicines. If you take a medicine that lowers cholesterol by binding bile acids, such as cholestyramine, colesevelam, or colestipol, take LIVMARLI at least 4 hours before or 4 hours after you take that medicine.

LIVMARLI is available in oral solution and tablet formulations. [00:12:30] LIVMARLI is taken by mouth, 1 time each day, 30 minutes before a meal in the morning. For the oral solution, be sure to use the provided oral dosing dispenser to accurately measure the dose of medicine.

These are not all of the possible side effects of LIVMARLI. For more information, ask your health care provider or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Please see full Prescribing Information, including Patient [00:13:00] Information and Instructions for Use, for LIVMARLI at LIVMARLI.com.

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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). Prescribing Information. Mirum Pharmaceuticals, Inc. 3. 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

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.

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.