For Patients With Alagille Syndrome, LIVMARLI Helps Keep Itch at Bay
OUTMATCH THE SCRATCH!
Cholestatic Pruritus Efficacy
LIVMARLI Provides Significant Improvements in Cholestatic Pruritus1
Significant improvements in cholestatic pruritus from baseline were achieved as early as Week 3 and maintained through 1 year in patients with Alagille syndrome taking once-daily LIVMARLI (P<0.0001).1,2
For patients who remained on treatment with LIVMARLI in the open-label extension (n=15), cholestatic pruritus responses compared with baseline were durable through nearly 4 years.1
IMPROVEMENTS IN CHOLESTATIC PRURITUS OVER TIME1,2
View Study Design and Select Baseline Characteristics
ICONIC is the first and only pivotal study of an IBAT* inhibitor in Alagille syndrome to demonstrate significant improvement in cholestatic pruritus1†
The ICONIC study assessed efficacy and safety of treatment with LIVMARLI in children ≥1 year old with cholestatic pruritus associated with Alagille syndrome.1,2
This study consisted of an 18-week open-label treatment period; a 4-week randomized, double-blind, placebo-controlled drug-withdrawal period; a subsequent 26-week open-label treatment period; and a long-term open-label extension period.1,2
Cholestatic pruritus responses to LIVMARLI were assessed through approximately 4 years.1
SELECT BASELINE CHARACTERISTICS1
|All Participants (N=31)|
|Mean age at baseline visit, years (SD)||5.4 (4.2)|
|Sex, n (%)||—|
|Genotyped mutation within JAG1, n (%)||31 (100)|
|History of receiving treatment for pruritus, n (%)||—|
|Any medication||29 (94)|
|Ursodeoxycholic acid||25 (81)|
|Trial parameter, mean (SD)||—|
|ItchRO(Obs) weekly morning |
average severity score‖
|CSS score||3.3 (0.9)|
|sBA, µmol/L||283 (211)|
*IBAT=ileal bile acid transporter.
†Mean difference –1.4 points [95% CI, –2.1, –0.8].1
‡Included a 6-week dose escalation period for all participants during the first 6 weeks of the open-label treatment period and for participants who received placebo during the RWD.
§Twice per day dosing was allowed after Week 100. The approved dosage of LIVMARLI is 380 mcg/kg once daily.
‖Average ItchRO(Obs) scores are based on the 7 days prior to baseline visit.
CSS=Clinician Scratch Scale; FSV=fat-soluble vitamin; ItchRO=Itch Reported Outcome; JAG1=jagged canonical Notch ligand 1; sBA=serum bile acid; SD=standard deviation; SOC=standard of care.
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) oral solution. Prescribing Information. Mirum Pharmaceuticals, Inc.
FSV supplements were available as SOC throughout the study. No changes beyond SOC in supplementation occurred during the study.1
During the first year of treatment, 84% (n=26/31) of patients with Alagille syndrome experienced clinically meaningful improvements in cholestatic pruritus compared with baseline with once-daily LIVMARLI.1
- “Clinically meaningful” was defined as ≥1-point ItchRO(Obs) improvement vs baseline (caregiver-reported pruritus score)1
At 1 year, improvements in cholestatic pruritus were correlated with decreases in serum bile acid (sBA) (r=0.47).3
POST HOC ANALYSIS:
During the first year, patients receiving LIVMARLI in the pivotal ICONIC trial had an increasing proportion of days with minimal to no itch.4
- In patients who remained on LIVMARLI (n=21) during the open-label extension (beyond 48 weeks), the median proportion of days with minimal to no itch was 95%4§
*Pruritus was assessed each day, in the morning and evening, using the Itch Reported Outcome (ItchRO) scale—a validated tool designed to assess the impact of itching in children with cholestatic liver disease, including Alagille syndrome. The ItchRO score is a 0–4 scale, where 0 is none, 1 is mild, 2 is moderate, 3 is severe, and 4 is very severe. Changes in ItchRO score of 1.0 or more have been shown to be clinically meaningful. ItchRO(Obs) was completed by caregivers and was the basis for the key pruritus endpoint. The patient-rated ItchRO (ItchRO[Pt]) was completed independently by participants aged 9 years or older and with caregiver assistance for participants aged 5–8 years.1
†Change from baseline, P<0.0001.
‡Included an initial 6-week dose escalation for participants previously receiving placebo.
§Based on mean daily morning ItchRO(Obs) scores in patients who remained on LIVMARLI through 4 years.
LIVMARLI has a well-characterized safety and tolerability profile for cholestatic pruritus in patients with Alagille syndrome who are ≥1 year old.5,6See the Safety Profile
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