Alagille Syndrome
Conference Roundup

Maralixibat shows promise in treating rare cholestatic diseases in infants under 1 year of age

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Maralixibat (MRX) has shown promising results in treating rare cholestatic diseases, specifically Alagille syndrome (ALGS) and progressive familial intrahepatic cholestasis (PFIC), in infants under 1 year of age, according to data presented at NASPGHAN 2023.

In the RISE study, MRX led to a reduction in serum bile acid levels and was well-tolerated in the participants, indicating its potential use in children as young as 2 months old. The trial also highlighted MRX’s well-characterized safety profile, supported by over 5 years of data in a substantial number of pediatric patients with cholestasis.

In the open-label Phase 2 trial that assessed the safety and efficacy of MRX in infants under 1 year of age diagnosed with ALGS or PFIC, a total of 12 participants (8 with ALGS and 4 with PFIC) with a follow-up period of 13 weeks were included. The participants ranged in age from 2 to 11 months, with a median age of 8.5 months.

Key inclusion criteria were the presence of cholestasis, gestational age of 36 weeks or more, and a body weight of at least 2.5 kg.

At the beginning of the trial, the average serum bile acid levels were 348 µmol/L for ALGS and 212 µmol/L for PFIC.

Of the 12 participants, 11 experienced at least 1 treatment-emergent adverse event (TEAE). Only 3 of these events were related to the study drug, all of which were categorized as Grade 1 gastrointestinal disorders and subsequently resolved. Most events were mild in nature, and none required a change in dosage.

In patients with ALGS, there was a mean change from baseline to Week 13 (CFB) in alanine aminotransferase (ALT) levels, with an increase of 148 U/L, primarily attributed to an intercurrent illness. However, this elevation promptly returned to baseline levels. In contrast, PFIC patients saw a reduction of 13 U/L in ALT levels.

In patients with ALGS, there was a CFB of -89 µmol/L, signifying a substantial reduction in serum bile acid. Patients with PFIC also experienced a notable reduction in serum bile acid, with a CFB of -72 µmol/L.

There were no cases of drug discontinuation throughout the trial. Furthermore, serum MRX levels were either below the limit of quantification or minimally detected, suggesting a well-tolerated pharmacokinetic profile.

Jankowska I, et al. Safety and tolerability of Maralixibat in infants from 2 months of age with Alagille syndrome or progressive familial intrahepatic cholestasis: Results from the RISE Study. Presented at NASPGHAN 2023.


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