In a 48-week clinical study called ICONIC, 31 patients with Alagille syndrome were treated with LIVMARLI to find out if it helped reduce levels of cholestatic pruritus and bile acids in the blood (known as serum bile acids, or sBAs). After 48 weeks, patients had the option to continue the study for up to 4 years.
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Relief through the first year
About 8 in 10 patients saw a big improvement in cholestatic pruritus* during their first year on treatment.
For many patients taking LIVMARLI, itch relief was seen at the very first assessment (Week 3).
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Reductions in sBA levels
About 8 in 10 patients had their sBA levels reduced by at least 20%†
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Improvements up to 7 years
About 14 of 16 patients (88%) who were still taking LIVMARLI in a long-term study saw their cholestatic pruritus improvements persist at 7 years‡
has been used by
patients
to treat cholestatic pruritus.§
- *Defined as an improvement in Itch Reported Outcome (Observer) (ItchRO[Obs]) score of 1 or more. ItchRO(Obs) is a tool designed to measure itch severity over time based on a 5-point scale.
- †24 of 29 patients (83%) experienced reductions in sBA during the 48-week period of the ICONIC study.
- ‡Based on data from MERGE, which evaluated results from 3 clinical studies to determine how long-term treatment affected cholestatic pruritus. These included data from 86 patients, including 23 who stayed on treatment for 7 years.
- §Estimation includes clinical studies, early access program, and commercial treatment. Not all patients taking LIVMARLI will have the same experiences.
The ICONIC study
ICONIC was a 48-week, multicenter, double-blind, placebo-controlled study, meaning the study was run in many locations, and patients and doctors were not aware which patients received LIVMARLI and which received placebo.
Patients were included if they were between 1 to 18 years old, diagnosed with Alagille syndrome, had serum bile acid (sBA) levels more than 3 times the highest level considered normal, and had moderate (or worse) cholestatic pruritus.
In the study, all 31 patients received LIVMARLI for 18 weeks, at which point some were switched to placebo. For those taking placebo, symptoms of cholestatic pruritus returned and bile acid levels rose within 4 weeks. At Week 23, all patients went back to taking LIVMARLI and their symptoms and bile acid levels improved.
Long-term data
Patients in the ICONIC study had the option of staying on LIVMARLI long term (up to 4 years). 23 patients entered the long-term part of the study, 15 of whom are included in the 4-year results.
The ItchRO scale
In the clinical study, patients kept an ongoing log of their itch using the ItchRO tool. This tool was used to measure itch severity over time based on a 5-point scale:
0
Not itchy at all
1
A little bit itchy
2
Somewhat itchy
3
Very itchy
4
Extremely itchy
Defining "improvement"
Changes in ItchRO score by 1 point or more represent noticeable differences in the itch; for example, a change from 3 to 2 means that a patient went from feeling very itchy to feeling somewhat itchy.
LIVMARLI may cause side effects.
Talk with your doctor about what to expect and how to manage any side effects.
Gastrointestinal (GI) events like diarrhea, stomach pain, or vomiting may occur as your body adjusts to LIVMARLI. Other common side effects include fat-soluble vitamin (FSV) deficiency, liver test abnormalities, and bone fractures. Learn more about safety with LIVMARLI.
Finley's mom, Dani, and dad, Jay, share a snapshot of their experience finding cholestatic pruritus relief with LIVMARLI. Watch Finley's full video.
Not all patients taking LIVMARLI and their caregivers will have the same experiences.
Jay: Finley started on LIVMARLI shortly after his first birthday 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 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.
Patients with Alagille syndrome were treated with LIVMARLI in 3 clinical studies (ICONIC as well as 2 additional studies called IMAGINE and IMAGINE-II), and some continued treatment long term.∥
- Data from these studies were later evaluated in the MERGE study to determine the long-term effects of LIVMARLI treatment. The MERGE study included 86 patients at the start of the study, with 23 patients completing the 7-year analysis¶
- In addition to cholestatic pruritus improvements, MERGE also evaluated sBA, growth, bilirubin levels, and liver enzymes called alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
How LIVMARLI affected sBA
sBA refers to the level of bile acid in a person's blood. High levels of bile acids in the body are associated with cholestatic pruritus. In Alagille syndrome, this bile acid buildup may also result in liver injury.
of patients (14 out of 16) who had experienced cholestatic pruritus improvements after starting LIVMARLI still felt significant relief.#
Overall, the 23 patients who continued LIVMARLI for up to 7 years saw improvements in sBA levels.
How LIVMARLI affected growth (height and weight)
Children with conditions that cause cholestatic pruritus can sometimes experience poor growth (shorter stature and decreased weight). Results from the MERGE study show that patients who stayed on LIVMARLI long term also saw improvements in their height and weight over time.
Patients grew taller and gained weight
within the first year of treatment with LIVMARLI. Improvements in height and weight continued through 7 years for patients who stayed on treatment.**
How LIVMARLI affected bilirubin, ALT, and AST
Doctors measure bilirubin, ALT, and AST to detect, monitor, and understand the severity of liver injury or disease.
- Bilirubin is a part of bile that forms when your body breaks down red blood cells. If bile is not flowing properly, bilirubin can build up in the blood
- ALT and AST are liver enzymes that help process proteins and are used as an indicator of liver health. When liver cells are damaged or inflamed, these enzymes can leak into the bloodstream, causing higher levels of ALT and AST in the blood
Lower bilirubin levels were seen through 7 years
of treatment with LIVMARLI.
Reductions were seen in both total bilirubin (all bilirubin in your blood) and direct bilirubin (bilirubin that your liver processed to exit your body).
No significant changes were seen in ALT or AST from the start of treatment in patients taking LIVMARLI.
Data from 3 long-term clinical studies for LIVMARLI were also assessed to better understand which factors may be linked to living longer without a liver transplant.
Patients included in the long-term studies:
Transplant-free survival
Transplant free means patients had not undergone a liver transplant. Transplant-free survival refers to the percentage of patients who are alive and have not gotten a liver transplant at a certain point in time.
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Patients who experienced a significant improvement in their cholestatic pruritus were also more likely to experience transplant-free survival.
of patients who had a >1-point reduction in their itch score
stayed alive and didn’t need a transplant
6 years after starting LIVMARLI.††‡‡§§
For those who did not achieve more than a 1-point reduction in their itch score, only 57% remained alive and did not have a transplant 6 years after starting LIVMARLI.§§
Unmanageable itch was a common reason for liver transplant in many patients with Alagille syndrome.
- ∥MERGE was a multicenter, open-label study, meaning the study was run in many locations, and patients and doctors were aware of the treatment being given. Some people chose to keep taking LIVMARLI long term because they felt it was helping them, even if they did not meet the study’s formal measures showing improvement in cholestatic pruritus.
- ¶ICONIC was a 48-week study of 31 patients. IMAGINE and IMAGINE-II were 72-week studies that included 53 patients. In all studies, those taking LIVMARLI saw improvements in cholestatic pruritus and sBA that lasted up to the end of the study.
- #Improvements in cholestatic pruritus defined as a reduction in ItchRO score of 1 or more. ItchRO is a tool designed to measure itch severity over time based on a 5-point scale. A total of 23 patients were evaluated for cholestatic pruritus improvements at 7 years.
- **A total of 23 patients remained on treatment at Year 7. Changes in height and weight were measured against the average patient Z-score at the start of treatment.
- ††The impact of LIVMARLI on transplant-free survival has not been established. No information about liver fibrosis (scarring) was collected.
- ‡‡Patients' itch was scored using ItchRO(Obs): a tool designed for caregivers to measure cholestatic pruritus severity over time.
- §§During treatment with LIVMARLI, 13 patients had a 1 point or greater reduction in ItchRO score. Five patients did not achieve more than a 1-point reduction in their ItchRO score.
How transplant-free survival was assessed
There were 3 clinical studies conducted for patients with Alagille syndrome. Some patients from those studies chose to stay on LIVMARLI long term. These patients were observed to see if there were any factors that could predict transplant-free survival.
Patients were included if they were 1 to 18 years old, had moderate-to-severe itch, were considered to be benefiting from LIVMARLI, stayed on treatment for at least 48 weeks, and had lab results at 48 weeks. All patients took LIVMARLI.
ItchRO and transplant-free survival
Patients used ItchRO to measure itch severity over time based on a 5-point scale:
0
Not itchy at all
1
A little bit itchy
2
Somewhat itchy
3
Very itchy
4
Extremely itchy
So, for those who had more than a 1-point improvement in their itch—for example, going from “very itchy” to “a little bit itchy”—93% were alive with their liver after 6 years of taking LIVMARLI.
For those who had a 1-point improvement in their itch or less—for example, going from "very itchy" to "somewhat itchy"—57% were alive with their liver after taking LIVMARLI for 6 years.
