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[00:00:00]

[music]

Dani: Really careful.

Jackson: You can try it by yourself.

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

Jay: My name's Jay.

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

Jay: Jackson's just [00:00:30] a mover and a shaker. He is a ball of energy. He's just always on the move, but 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 Finn [00:01:00] though. Not with Finn. Good job, Finley.

Jackson: [unintelligible 00:01:05].

Dani: We were very excited to add another little baby to our family. So we got pregnant with Finn. Something that was supposed to be joyous ended up turning into not that.

Jay: In that 20-week 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 was going [00:01:30] on. So 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 ninth 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 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 one moment where [00:02:30] it set in that like, "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 a lot [00:03:00] 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 kind of [00:03:30] told us, "We don't really have an answer," but that's when we really first heard of Alagille syndrome and that it might be something that Finley has. [00:04:00]

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, but 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, jaundice 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. Then the scratching of the eyes or grabbing at the ears, all those are normal hunger cues, sleepy cues. 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 2 to 3 hours, well before that 6-hour mark that our doctor told us that hydroxyzine would last. The itch impacted Finley's life. That period of time is 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, dark time. [00:06:00]

Jackson: Do you want to try? Do you want to try and [unintelligible 00:06:04]? [unintelligible 00:06:06]. Oh, look at that.

[laughter]

Jackson: [unintelligible 00:06:12] he's going to do it. He's going to do it. No. [unintelligible 00:06:15] try it by yourself. You can try it by yourself.

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 Alagille, [00:06:30] 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 it 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 hands 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 4-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. He just had more time to be Finley and it's really awesome.

Dani: It was nice to see him be able to focus on something else outside the itch. We want him to thrive, be a child who isn't impacted by the itch through liver disease. We just want him to be a normal 1-year-old child. Our doctors shared that there could be [00:07:30] 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.

[music]

Jay: I think we've really tried to just see how much [00:08:00] has changed in the time he's been on it with the itch subsiding and going down that it 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 it, 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, makes me happy. It makes us smile.

Dani: Just because he has been [00:08:30] dealt a certain hand in life, that doesn't mean his rare disease defines it. 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 and look a little different, but he's still capable of doing what anybody else is. [00:09:00] 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 diseases 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.

Dani: Yes.

Female Speaker:

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, [00:10:00] 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 [00:10:30] 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 [00:11:00] 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, [00:11:30] 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 [00:12:00] 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 [00:12:30] 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.

[music]

[00:13:00]

[00:13:15] [END OF AUDIO]

[00:00:00]

[music]

Téa: My name is Téa. This is my dad, [00:00:30] Armin. This is my mom, Michelle. This is my grandpa, Peter, and this is my dog, Lulu. I have a sister named Isla. She lives in Arizona, a long way from me. She is a very good sister and I love her to the moon and back. This is Peppermint and this is Kiwi, and that's [00:01:00] my family. I was born with Alagille syndrome, and it hurts, and it's painful and your body tells you to itch, and I'm trying to stop.

[music]

Michelle: When I first found out that Téa had Alagille syndrome, [00:01:30] my heart broke, and I was lost. I felt like everything that I've always wanted, not that it was taken away from me, but that joy of a newborn and having a baby in your arms, it was so hard. It was hard on us. It was hard on our marriage.

Armin: I think I was in denial, and I still might be. My first instinct was, [00:02:00] “why?” We didn't know what to do.

[music]

We were just lost. The girl that you always want, seeing her going through something that no kid should go through, so tiny, so small, it was hard.

Michelle: When we heard about her condition, they were saying, [00:02:30] “there can definitely be lots of itching.” She was 3 months old when she was diagnosed. She couldn't tell me that she was itching, so I really had to look for the signs. There was lots of itching and wiggling around. The physicians described it to me as having internal itching. It's almost like having poison ivy inside your body. For her, it was a lot of reaching for the ears, lots of scabs, lots of bleeding and same with the head. She would take both of her hands and [00:03:00] just scratch.

Armin: She couldn't sleep. She would scratch all night and you as a parent don't know what to do, how to help them. We would get up and just scratch her until she goes to sleep.

Peter: My daughter, she goes to work. She brings the baby by us. We have a crib for her, and we put them in a bed, the same house she laying down and her hands go all around in the [00:03:30] body, more time go in her legs, back, all over.

Téa: At nighttime, the itching was the worst on my ears, my legs, and my toes. That was the worst part of the night. In the morning, I would wake up and I would see that there's blood all over my sheets. I said to myself, "why am I the only one who has this?" [00:04:00] At school it was hard, during PE class I think that was the worst time of the day that I itched. Some kids at school were not being very nice, and I did not like it. I would say to the kids who were not being nice to me, I would say, "you should understand that I have Alagille syndrome and now I'm itching and I can't help it. [00:04:30] I don't know what to do."

Michelle: I categorized her itch as mild, and I think because I just made it so—it was so normal, it was just a part of our life at that point that I regret it because it wasn't normal. It was affecting her daily life. There was an opportunity for us to get into a trial with [00:05:00] LIVMARLI. Téa wasn't able to access the trial because I categorized her as mild. Hearing other people's stories on their itching, I was like, “okay well, she's not doing that. It's not that bad, or if it's cool in the home, she's not itching that bad.” I always found something to be like, “okay, it's not that bad,” but in reality it was. [00:05:30]

[music]

Michelle: We first learned about LIVMARLI through the clinical trials, so we knew that there was something in the works for itching, which we were really excited about. Téa started LIVMARLI in February of 2022, [00:06:00] when she was 8 years old. After about 14 days on LIVMARLI, we noticed a drastic change in her itching. Her first night we knew that LIVMARLI was working for her. In the middle of the night, I didn't hear her itching, and she was snoring, and it was so funny to me, but also very sad to know that it took 8 years [00:06:30] for her to sleep all night without sitting up and itching in the middle of the night. In the morning, she ran into my room and she's like, "Mama, I slept so good."

Armin: That night was definitely one of the best nights of our life. Just hearing her snore and sleep and not itch. [00:07:00]

Michelle: When she gets home from school, she's not running to take her socks off and itch. She is itching less and sleeping through the night, which is amazing for her. She doesn't have the blood on the sheets like we did before. She's rested. She's happy.

Peter:: Now, Téa is taking LIVMARLI, I feel so happy. It’s helping her. She’s not scratching. She sleeps good. [00:07:30] She's full energy.

Téa: LIVMARLI helps me sleep better because I itch less. I'm not scratching and it makes me feel better, and I'm excited that I can do more things.

Armin: Tell me when it's sauce time.

Téa: Okay.

Michelle: When Téa was prescribed LIVMARLI, I received a call from Mirum Access Plus, and it was just a rundown of the [00:08:00] medication, potential side effects, how delivery was going to work, if I had any questions or concerns, who to call, and quite frankly, it was probably the easiest start of a new medication I think I've ever been through. We received our first dose of LIVMARLI 2 weeks after I spoke to Mirum Access Plus. We went through, it was approved through insurance, and we received front door service of our prescription. [00:08:30] Our doctor did mention that there were some side effects with LIVMARLI.

Téa did experience some cramping, stomach cramping, but those have now subsided. It's better to talk about it than to hide from it, and it's good for her. It's good for us, and it's good for our family. [00:09:00] We were never ashamed, but it was almost like you're almost in denial. There's more people out there like us who are like, we don't want to talk about it. Let's just keep going. I definitely feel like the Alagille Syndrome Alliance is such a great—there's so much amazing information. Roberta is very communicative on the Alliance [00:09:30] and it's just a great resource, and it's amazing to see how many kids there really are and you're not the only one that's feeling this way.

[music]

Armin: Advice that I would give other dads going through this, would be to be strong; do a lot of research. Be there for your kids; don't look at your kids [00:10:00] any other way, as they're not normal. They're the same as every other kid. Spend as much time you can with them.

Michelle: If I can give other caregivers advice, it would be, join the Alagille Alliance. It really makes a huge difference. Build that relationship with your physician. They're all different. Find one that suits you and your family because it really made [00:10:30] a huge difference for us. There's light at the end of the tunnel. He might not know everything, but that light just seems a little bit brighter.

[music]

Narrator:

INDICATION

LIVMARLI is indicated for the treatment of cholestatic pruritus in patients with Alagille syndrome (ALGS) 3 months of age and older. [00:11:00]

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. [00:11:30] 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. [00:12:00] 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 [00:12:30] 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 [00:13:00] 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 [00:13:30] 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 [00:14:00] remaining LIVMARLI should be discarded 100 days after first opening the bottle.

[music]

[00:14:25] [END OF AUDIO]

[00:00:00]

[music]

Terisa: My name is Terisa. I have 3 boys. The oldest, Brian, is 14, Tyler is 10, and Benny is 5. [00:00:30] I think that being a mom is probably what my calling's been. I love being their mom. I love being just involved with raising them, and it's what I've always wanted to do. I've always wanted to have kids. I didn't really know what I wanted to do with work. I just knew I wanted my job to be being a mom.

The most rewarding thing is just watching them grow up, just seeing their different personalities, and they're so unique. They all have their own character traits, their own interests. Tyler's hobbies are swimming, playing basketball, [00:01:00] throwing the ball around with his brothers, he likes to do that, likes to cook with me. We like to just hang out and watch movies and videos and he loves video games. That's his favorite thing right there.

When I was pregnant with Tyler, they did a very thorough check, the 18-week fetal survey, just to be proactive since I was born with a heart condition. That's when they found the hole in his heart and some issues, and they diagnosed him prenatally with [00:01:30] Tetralogy of Fallot. He was born at 39 weeks and everything looked good, and they took an X-ray of his heart and that's when I saw the butterfly vertebrae, which is now knowing that that's the first marker that we found for Alagille syndrome. And then, he went home, and we just were looking forward to surgery day and that was it.

He started getting really jaundiced even though he was eating really well. The pediatrician had just run some basic bilirubin tests and he was [00:02:00] really high, but he didn't think it was dangerously high to send him to the hospital. We were going back and forth between cardiology for a week and then pediatrician for a week just to make sure his heart was stable until he was ready for surgery. The morning of pre-op, they just threw on a liver function panel test just to see if the bilirubin dropped.

Next thing you know, surgery's canceled and he is whisked upstairs for a liver ultrasound. Then, that's where they were able to diagnose the bile duct paucity. [00:02:30] They went right from there and clinically diagnosed him with Alagille syndrome.

[music]

When he was diagnosed with Alagille syndrome, I just remember standing there and everything spinning around me. [00:03:00] I just felt like I was in this tornado of like, "What? This just happened to me? I just did everything you told me to do and now I have this diagnosis."

[music]

The light in the tunnel there was finding the Alagille support page and finding people that were going through exactly what I was going through and being able to also connect with families that had the same age child as my kid. It was great to see adults and say, [00:03:30] "Wow, these kids have a future." Ironically, it felt very comforting to have someone on my side.

[music]

Learning about bile acids through the Alagille support page, I realized that that was a big factor to his itch. Basically, your liver has no natural flow of the bile, so it just reabsorbs and it's going through your bloodstream, so everywhere your blood is from head to toe [00:04:00] is going to be itchy. I started noticing him rubbing his eyes a ton. It was more than just the hunger cues, more than the tired cues, and so we went back into another pediatrician and asked, “What's going on?” They said, "No, it's not allergies. He's got to go through a whole season before it's diagnosed as allergies." It was just brushed off as, "We don't know what that is."

The itch was getting worse and every time we did a diaper change, he was scratching at his legs or his diaper area and then rubbing the eyes [00:04:30] constantly. That was the big thing for him. Then, it moved into putting toddler socks on his hands so that they went all the way up to his arms; that way, at night, he wasn't digging into his ears and making them bleed everywhere. The itch kind of normalized for us. We just knew it was there, but at the same time, we really kind of discredited a lot of the itch and a lot of the liver involvement to just being mild, even though we later learned that it was [00:05:00] much more severe than mild.

It just was changing bedsheets consistently, bandaging up all the cuts. Unfortunately, grieving the fact that I couldn't do the bed sharing and the cuddling with Tyler because he sweats so much and then it made him more itchy. Then, trying to sleep with him, he was tossing and turning and rolling and scratching, and I was like, "I can't do this. I'm not sleeping. He's not sleeping." Naps were few and far between. Just was never settled for a nap time because he was so itchy and there was no [00:05:30] medications out there at the time for Tyler to take that actually worked for him to relieve that itch.

Tyler: The itch is just bad. It's horrible and it keeps me from doing stuff. The itch just feels like an itch, a bug bite, or something. But then, it goes from here to your back, and then goes all over, and then you can't stop.

[music]

[00:06:00]

Terisa: We had learned that LIVMARLI was getting close to being FDA approved and we were very excited about something being an option for him again. We worked with our doctor [00:06:30] and got him on LIVMARLI. Tyler was a good candidate for LIVMARLI because he had Alagille syndrome, but then he had that very persistent pruritus. When he turned 10, he started LIVMARLI and that was great. It was a really fun day for him because it was his birthday, but also it was kind of the start of what could be his new normal, not itching as much as he had been.

On his 10th day was when we started realizing he's sleeping through the night. He's not tossing and turning. [00:07:00] There had been no new scabs, no bandages on his arms and legs. That was a sight to see to not have the bandages so much, but then also just to see him sleeping and his brothers sleeping because they all shared a room and they weren't being woken up by him tossing and turning so much. Once his doctor prescribed LIVMARLI, we got connected with the Mirum Access Plus Program and they got it right on our doorstep in less than 2 months.

It's been nice to not have to be chasing down doctors [00:07:30] for refills and going to the pharmacy to pick things up. It's just so convenient having it right to our door. One side effect that we've been battling is GI cramping. That's just something that we knew it was a possibility of this happening and we had to work with our doctor to make sure that we could manage this for him and let it be so that he could still attend school and do his daily activities. [00:08:00] I think he's great now. I mean, we're going strong on 10 months in. What do you think?

Tyler: I think we're doing good.

Terisa: You feel good on the medicine?

Tyler: Yes.

Terisa: I know 10 years is a long time, but I'm glad he wasn't 20 and he just got his hands on this. I wish it could have been sooner for him, but I'll take 10 years and then the rest of his life.

Tyler: Having Alagille syndrome doesn't really make me feel [00:08:30] much different. It just makes me feel like myself because it doesn't affect what's on the outside. It mostly affects what's on the inside. Now that I'm on LIVMARLI, I'm itching less and I'm sleeping better.

Terisa: There's people out there that are willing to connect and happy to connect and make sure that you feel supported through your journey because at the beginning, it can be very overwhelming and you can feel like you're drowning, but there's light on the other side and there's [00:09:00] a possibility of having happiness as part of your every day.

[music]

Narrator:

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 [00:09:30] 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. [00:10:00]

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, [00:10:30] 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 [00:11:00] 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 [00:11:30] (≥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 [00:12:00] 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. [00:12:30]

[music]

[00:12:40] [END OF AUDIO]

[00:00:00]

[music]

Téa: Hi.

Dr Bass: Wow.

Téa: How are you?

Dr Bass: Oh, this is so nice.

Téa: I just wanted you to come. I-

Dr Bass: Oh, this is great.

Téa: -wanted to-

Dr Bass: Can I sit here?

Téa: -surprise you. Yes.

Dr Bass: Oh, great.

Téa: I wanted to surprise you.

Dr Bass: You did. I'm so surprised. This is amazing. What are we going to be doing here? This is great.

Téa: [00:00:30] I'm going to be asking you some questions and I'm going to be interviewing you.

Dr Bass: Oh, wow. Okay.

[music]

Téa: If you could only eat one food for the rest of your life, what would it be?

Dr Bass: See, I have a hard time with this because there's foods that I love. I probably would say either pizza or french fries.

Téa: Okay. Good job. Who's your favorite superhero? [00:01:00] Batman.

Dr Bass: [laughs] You knew this.

Téa: I knew.

Dr Bass: You knew this, I like because he's smart and he has all these gadgets that he creates. It's really cool.

Téa: You're smart.

Dr Bass: I like the fact that he could—that he didn't have a power, he had his mind.

Téa: Yes. What is Alagille syndrome in your own words?

Dr Bass: Alagille syndrome is a condition that you're born with [00:01:30] and it impacts the ability of some parts of your organs to form. Alagille syndrome can cause you to have problems with your liver or with your heart or with your kidneys. One of the things with your liver that it can impact is that it can cause difficulty in getting something that your liver makes called bile. Bile is this yellowish liquid that dissolves fat. When you eat something that [00:02:00] has fat in it, bile is what's breaking it down and that bile backs up in the setting of Alagille syndrome and that's what causes some of the symptoms of Alagille syndrome.

Téa: How did you know that I had Alagille syndrome?

Dr Bass: When you were a little baby you had jaundice, meaning you had elevated levels of bilirubin and your skin looked a little yellow and your eyes looked a little yellow. [00:02:30] There was a genetic test that was done that demonstrated that you had Alagille syndrome. Then we took care of you and tried to help you through that time and you've done really well since that time.

Téa: Why do kids like me with Alagille syndrome itch?

Dr Bass: That's exactly it. There's not enough tubes for that bile to flow through and so it goes into other parts of the body. [00:03:00] You may not even notice that you're itching, but for some people it can feel like they're wiggly, it can feel like they are just scratching distractedly. They don't even know. (This is my example of doing this.) But it's the bile that's in their bloodstream that's causing that to happen because there's too much of it and the liver can't put it all down through the bile ducts or the tubes into the intestine.

Téa: What do you tell kids like [00:03:30] me and their families to look for with the itch?

Dr Bass: There's a lot of different aspects and it's important that, as a doctor, I understand that itch can be impacting a lot of patients, because I see you—and I love seeing you when I see you—but I see you for 30 to 60 minutes a couple of times a year and so I get a really [00:04:00] small snapshot of your life. And if I'm not asking, "How are you sleeping? How's it going in school? Can you pay attention? Can you sit at the dinner table and eat? What happens when you're watching TV? Are you paying attention or are you potentially itching and distracted by it?"

It's important to me to make sure that I'm asking those questions that might be impacting you. [00:04:30] When you say what's important for you, it's to make sure that you communicate to me what's your life like, what is your daily life like, and how we can help understand that because that helps us understand how we can treat this.

Téa: Does your other patients feel like they're grasping their arm and go itch?

Dr Bass: I don't know that I've heard that exact [00:05:00] description. The things that I look for is sometimes I come in the room and I'm talking to mom, but I'm looking at you. I want to see what you're doing when you're just sitting there, just like listening. So I see what the patients are doing and trying to make an observation of what's going on. It's one of the ways I can rate how kids are itching or if kids are scratching [00:05:30] and watching what they're doing as they're going.

Téa: Why did you decide that LIVMARLI was right for me?

Dr Bass: I was very ready to give you LIVMARLI as soon as I saw the FDA approval for it. I knew that you were doing okay. We had you on medicine that was keeping you okay, but I also knew that you weren't perfect. I knew that you would itch a lot. I knew that you would sometimes [00:06:00] have scratches on you when I would see you in the office. The medicines that we were using didn't seem to be enough to take away your itch and so my hope was that I could use LIVMARLI to improve that symptom for you.

Téa: How does LIVMARLI work?

Dr Bass: What LIVMARLI does is it blocks the absorption of bile acids in the lower part of the intestines. When your liver—I almost like to think of this: Have you ever been to a water park?

Téa: Yes.

Dr Bass: Okay. The way I like to think about this, the [00:06:30] bile is all going down this big water slide and what do you do at the end of a big water slide?

Téa: You go in the water.

Dr Bass: You go in the water, and then what do you do right after that? You get up and you want to go right back up the water slide, right?

Téa: Yes.

Dr Bass: That's really what's happening with all the bile. All the bile goes through and then it goes right back up to the liver, but if there's not enough tubes for that bile to flow, then that bile goes into the rest of the body. What LIVMARLI does is it blocks the ability of that bile [00:07:00] to get out of the water and go back up to the slide. It allows it to leave the body. That's how it works.

Téa: How do kids like me know if LIVMARLI is working?

Dr Bass: For you, you should hope that you feel less itching. You should hope that you should sleep better. You should hope that you have less irritation and agitation. If sometimes [00:07:30] kids have some jaundice and hopefully that should go away too. For me, I can measure the bile in your blood and so one of the things that I've done as we've done some of the blood tests, and I know you don't love the blood test. As we've done that, we've measured and we've found that your bile acids, which were high, are much lower now on the LIVMARLI, so that improved things. Certainly, there are some side effects that can occur with LIVMARLI as we talked [00:08:00] about. When I talked about the blocking the absorption of the intestine in the bile well, and we get that bile out of your body.

How does stuff get out of your body? One of two different ways. You either go pee or you go poop and so it goes out through your poop. Sometimes people have to go to the bathroom and go poop more. They might have some diarrhea. They might, if they feel like they have to go poop, sometimes they [00:08:30] feel like that they have a little bit of pain and sometimes they can, sometimes even have a little bit of nausea and throw up but in reality, my experience has been that people have tolerated it really well so far.

[music]

Téa: When I went in, when I was younger, I used to be very scared. But since I got older, I was so happy that I got to see you [00:09:00] more and more often, and that's the memories I have with you.

Dr Bass: Yes. I remember now actually it's really nice to see you grow up because at one point you were happy to see me and then I would examine you and you wouldn't like that I was doing anything. Now you actually are very informed about what's going on with your body and you're asking questions and you're taking [00:09:30] some ownership of that. That's really going to be useful for you, for your health going forward if that's a really good habit and thing to have for you.

Téa: That's amazing.

Dr Bass: I always look forward to seeing you guys. As a doctor, I don't do this for thank-yous. I do it because I like doing it, but when I get thank-yous and appreciation from families, it's [00:10:00] really a wonderful thing and it keeps me going, and you and your family and your mom, your grandpa, you always show appreciation.

Téa: You have made me happy for the last—for my whole life. You always make me happy. You are just the best doctor I could ever have. I'm very, very glad you came here today.

Dr Bass: I am so glad I came here. I'm so glad that [00:10:30] we could sit and talk like this. This has really been wonderful.

[music]

Dr Bass: First off, what is your favorite sport or activity outside of school?

Téa: Gym.

Dr Bass: Gym? What do you like to do in gym class?

Téa: I like to do cartwheels. I like to do the splits.

Dr Bass: Okay.

Téa: I like to run, and I like [00:11:00] to do—I like to exercise.

Dr Bass: Excellent. Now do you do cartwheels, or do you do roundoffs, because I learned that there was a difference?

Téa: Yes, roundoff.

Dr Bass: Roundoffs? Excellent. When you had the itch, what did it feel like to you? How did you feel it inside?

Téa: It felt really bad. It felt like something was in my body, and when I was younger, I didn't know any of this stuff, but now since I'm getting older and I know what's in my body and LIVMARLI is [00:11:30] helping.

Dr Bass: That's wonderful. Did you have certain times of day, like morning it was worse, right before you went to bed it was worse? What was—Did you have [crosstalk]

Téa: I think night was the worst.

Dr Bass: Nighttime was worse? Okay. This is actually a really good question, I've never asked you this before. How would you describe Alagille syndrome to your friends?

Téa: I would describe that I have Alagille syndrome [00:12:00] and sometimes they would ask me, "What is that?" "It's something that makes you itch a lot and you can't stop, and even though you're trying to stop, it's not working."

Dr Bass: Okay.

Téa: Now that I'm taking LIVMARLI, it's helping, and you guys don't see me itching more. You just see me itching less.

Dr Bass: That's good. That's a good description. I like the description. What advice [00:12:30] would you give other kids with Alagille syndrome?

Téa: I would say to ask your doctor if you can have LIVMARLI like me.

Dr Bass: Okay. That's great. One of the other things that I was curious about is would you tell other kids to say, "Don't be afraid to talk about the itch"?

Téa: Do not be afraid.

Dr Bass: Yes.

Téa: You tell anybody.

Dr Bass: Right, because people don't know they should tell people. We want other kids to know that they can talk about what they're feeling.

Téa: Yes. [00:13:00] Anybody you know, you immediately tell. It's better than just keeping it away.

Dr Bass: Excellent. Well, those are all the questions I have for you.

Téa: Well, I have a special guest coming named Mom.

Dr Bass: Really?

Téa: Yes.

Dr Bass: Oh, wow. I'd love to see her.

[music]

Téa: Yes, she's coming.

Téa's Mother: Hi.

Dr Bass: Hi.

Téa's Mother: Hi, Dr Bass. It's so good to see you, Dr Bass.

Dr Bass: Yes.

Téa's Mother: I definitely wanted to just thank you—[tears up] [00:13:30]

Téa: For everything?

Téa's Mother: [laughs] Sorry.

Dr Bass: It's okay.

[silence]

Téa's Mother: Not only are you her doctor, but you're just such an amazing person. You saved her, you saved me. I would hope everybody has relationships with their doctors as we do with you. It was hard at first. We couldn't find a doctor that was just [00:14:00] a right fit. You're our third doctor that we saw and I would never change you. You speak to me like a human. Sometimes the scientific words get out of hand and you never do that to me. You talk to me, you draw me diagrams, and we appreciate that.

You hold such a special place in all of our family's hearts and everything that you have done for us. Nothing in the world can ever [00:14:30] repay you what you have done for Téa mentally, physically, and for all of us. Téa loves coming to see you. A lot of kids are scared of their doctor, and they don't really talk to them, but no, I've seen you dance in the room with her and you make her laugh, and your jokes are funny.

[laughter]

She talks about you all the time. She loves to come see you and that's [00:15:00] huge. It's so heartfelt. When she tells everybody and she's like, "I'm going to go see Dr Bass, he's my favorite." It means a lot as a parent for her to be, not just you, the whole team. She's so excited to see your team and your nurses and she knows that there's a special place for her there. The fact that she's excited to come there is all I can ever ask for, and I can't thank you enough.

Dr Bass: [00:15:30] For me this is why I do what I do. It's to see her grow up. It's to have the ability to see her really sick as a baby and to get her better and to see her like this today is the biggest reason that I do what I do to have a relationship with you guys. It's not just you, it's the entire family. It's all Team Téa and [00:16:00] has been just amazing to work with you. Then the advocacy to be like, we know there's something better out there for her. We know we can do this. We know we are watching for this and being able to try and find the next thing to help her get better, which is how we got to this today with this drug, is that we're working together to do it.

Téa's Mother: I agree.

Dr Bass: For her, and of course the [00:16:30] most important thing is her.

Téa's Mother: Always. [laughs]

Téa: Would you like some tea?

Dr Bass: I would love some tea.

Téa: Here is your tea, here is your coffee and—

Téa's Mother: [laughter] Can we get a cheers?

Téa: Yes. Let's do it. [crosstalk] Cheers.

Speaker 3: [music]

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 [00:17:00]

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 [00:17:30] 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. [00:18:00] 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 [00:18:30] 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 [00:19:00] 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 [00:19:30] 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. [00:20:00] Any remaining LIVMARLI should be discarded 100 days after first opening the bottle.

[00:20:26] [END OF AUDIO]