Emma and Abby | LIVMARLI® (maralixibat) oral solution and tablets | HCP

Emma and Abby share their young-adult perspectives on growing up with cholestatic pruritus and how LIVMARLI helped relieve their symptoms

Video of Emma and Abby

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[00:00:00] [music]

Emma: I'm Emma, I'm 19, and I'm from Washington State. I was diagnosed with Alagille syndrome very soon after birth. [00:00:30] I had the symptoms of jaundice, prominent facial features, and low bile duct count. When I was about four or five years old, I realized I had Alagille syndrome. That meant for me that I had a lifelong illness that I had to manage.

One of the main symptoms for Alagille syndrome is cholestatic pruritus. My itch was pretty severe. It's kind of like [00:01:00] bugs under your skin, almost. It's just something you constantly have to soothe, and you just can never soothe it. Daily life for me would be very disrupted. I would have to itch before I even went into public. I managed the itch by scratching, or if it was a lot, I would take ice baths and lotion and stuff, but they're temporary relief.

It was hard to maintain friendships and relationships with people, along with schooling. It was very [00:01:30] hard to focus because my main focus was just the itching. It's very sensory, overwhelming. The itching just became my everyday life. No matter how severe it was or how bad it was, that was just my life. I just lived with it. Looking back, I'm like, that was not normal. I got on the clinical trial for LIVMARLI when I was 12. I'm 19 now, so [00:02:00] that was like seven years, I've been taking it every day since then.

Abby: I'm Abby. I'm 26 years old, and I'm from Huntsville, Alabama. I was 11 months old when I was diagnosed with Alagille syndrome. The symptoms that led me to being diagnosed was I was itching from the time that I was able to start to itch, I was not growing, and I was jaundiced. [00:02:30]

I believe at the age 10 and 11, I started to understand what Alagille was and what it meant for the rest of my life. I knew that I was always going to have something wrong with my liver, and I knew that I was always going to have to go to doctor's appointments and take medication. Those were just some of the symptoms that stood out to me.

My itching would start bright and early in the morning and progressively get worse throughout the day. Some of the medications physicians [00:03:00] were offering me were cholestyramine and hydroxyzine. They had me on rifampin at one point, and none of those helped. At around almost two years old, I had a biliary diversion, and I lived with that for my entire life until I was 19.

Even with the diversion, the itching was still there. I still scratched my feet on the carpet, [00:03:30] the palms of my hands would itch, my legs would itch, so I would still have to try to use other methods to help my itching. It was very difficult to go to school, and have social interactions, and do things. As a kid with the pruritus, you feel very alone a lot of the time.

Looking back, the pruritus has always been normalized for me. It was just something I had to live with. I have a really good support system, always have, but I think [00:04:00] that I wish I had physicians advocating a little bit more for me because the pruritus is a real thing. It is very debilitating. It is awful. I encourage anyone that your pruritus affects your day-to-day life and that you have normalized it, to talk to your physician and let them know how it affects you and see where you can go from there. [00:04:30]

Emma: Hello.

Abby: Hey.

[laughter]

[music]

Emma: At what point did you realize how bad the itching was? Did you find that out, or someone else had to point that out?

Abby: I always knew it was bad. I always knew it was bad. It was no secret. I feel like when [00:05:00] my husband and I went to a doctor's appointment maybe two years back. He asked the doctor if there was anything that would help with the itching. I think that's really when it was like, "Oh, okay. It really is that noticeable and that bad."

Emma: I feel the same way with I knew it was bad, but I think it was me seeing the reactions of other people. We go in public. My mom would get so stressed. She's like, "Stop itching, stop itching." She'd whisper it to me. I'm like, "I didn't even [00:05:30] know I was doing it." At school, I remember I liked this one boy, and I'd be talking to him. He's like, "What are you doing?" I find out I'm doing this the whole time while I'm talking to him. At what point did the itching get so bad that you're like, "I need to get something, like treatment"?

Abby: My parents made that decision for me early in life. I had the diversion done, but then when I was 19, I got it reversed. After the reversal, [00:06:00] I knew that it was going to be tough because even going from one thing to another, your body has to have time to adjust. I tried several different things, like the allergy medications you can take. Nothing helped me sleep all the way through the night if I was having a bad day. I think I remember we used an anti-itch lotion, and I don't remember it helping any at all.

[music]

[00:06:30]

Abby: How did you hear about LIVMARLI, and how old were you, and how did that all come about?

Emma: I was about 5th grade. My mom's always been a big advocate. She's always on the hunt for something. She found about LIVMARLI. I got in the clinical trial. I was in that for about a month before I got on the medicine. We took a week or two. Then I started [00:07:00] seeing results. What about you? How did you hear about LIVMARLI?

Abby: A physician reached out to me to educate me about LIVMARLI. Then the physician got in contact with my doctor after I said I was willing to do it, and then I was able to start on it. I'm very glad he reached out to me. If he didn't, I don't think I would be in the place I am today. I'd still be itching all the time.

Emma: I don't [00:07:30] know what my life would be like. I don't really want to go back to the itching.

Abby: That's how I feel, too. I feel like I lived my whole life with it. I don't want to go back.

Emma: When I started taking LIVMARLI for the first couple weeks, I noticed myself I didn't need as much time itching, or I could focus in class. That was a big one where I wasn't constantly fidgeting.

Abby: Before I started, noticing I'm being able to sleep better and [00:08:00] stay asleep all night long. Before, sometimes I would wake up in the middle of the night and have to scratch or itch my feet. I think it took about 3 or 4 weeks before I could actually sleep throughout the night.

Emma: I think it was the conversations I had with people. My mom, especially, I'd be talking to her. She's like, "You haven't itched once in the last 5 minutes." I'm like, "I haven't?" I've just not been doing it. I've been sitting perfectly still.

Abby: I think mine was [00:08:30] more at work because I sit in a cube all day. I would get antsy and you want to itch. When I was sitting at work all day long and haven't itched a single time, I was like, "Wow." I felt better. I was able to sleep, and I wasn't so groggy in the mornings because I was able to sleep, because I'm not itching as much.

[00:09:00] My physician told me of several different side effects while taking LIVMARLI, including stomach pain, diarrhea, vomiting. I only experienced stomach pain one time, and it subsided after eating a larger meal. Why do you think it is important to take LIVMARLI every day?

Emma: It helps me manage my itching. It just lets me go without—my daily life without worrying about the itching as much. What about you?

Abby: I want to live my [00:09:30] life like this. I love to travel. I love to go do things. It's very important to me to manage my pruritus and make sure my itching is at bay.

Emma: Why do you think it's so important for us to talk about the pruritus?

Abby: Because I think that a lot of people struggle with it, and I think that a lot of people feel like there's no way out of it, and they have no hope. [00:10:00] I think it's really important to talk about your experiences and how you've dealt with it, and then where you are now so people can understand there are opportunities out there and there is hope.

Emma: There was a lot of unknowns when I was growing up. I didn't know what was going to happen. I didn't know what to do. Seeing someone else's experience is like a nice guide, a shining light in the dark.

Speaker 3:

INDICATIONS

LIVMARLI (maralixibat) [00:10:30] 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 [00:11:00] 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 [00:11:30] (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 [00:12:00] 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 [00:12:30] 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 [00:13:00] 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 [00:13:30] 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 [00:14:00] 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.

[00:14:30] 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 and 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 [00:15:00] 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 at LIVMARLIhcp.com.

[music]

[00:15:30]

[00:15:36] [END OF AUDIO]

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.