Author: Lynda Williams
medwireNews: Further findings on the efficacy and safety of ileal bile acid transporter (IBAT) inhibitors for patients with progressive familial intrahepatic cholestasis (PFIC) have been presented at the 2024 AASLD The Liver Meeting in San Diego, California, USA.

The updates include a late-breaking abstract poster on the long-term efficacy and safety of odevixibat and an oral presentation on the relationship between improvements in pruritus and growth during maralixibat therapy.
Richard Thompson (King’s College London, UK) and co-workers reported a late-breaking abstract with efficacy data from an integrated analysis of the 116 patients participating in the PEDFIC 1 and/or 2 trials, including 30 patients who had received around 152 weeks of treatment with odevixibat and 12 patients who had received around 216 weeks at time of analysis.
“In patients with PFIC on long-term odevixibat treatment, there were clinically meaningful improvements in pruritus, as well as reductions in sBA [serum bile acid] levels across PFIC types: improvements occurred rapidly and were sustained for those remaining on treatment,” the researchers said.
This included a decrease in scratch severity and an increase in the rate of pruritus response, defined as at least a1-point reduction from baseline, from 61% after 72 weeks of treatment to 88% after 96 weeks, while sBA level response, defined as no higher than 70 µmol/L or at least a 70% reduction from baseline, was 45% at 72 weeks and 58% after 96 weeks of odevixibat.
Compared with baseline, patients given odevixibat experienced improvements at 72 weeks in their height and weight Z-scores and the quality of sleep, as assessed by the number of wakenings and daytime tiredness.
There were no new safety signals during follow-up, with most treatment-emergent adverse events (TEAEs) mild or moderate and unrelated to treatment.
A second update from the PEDFIC 1 study, presented by Tassos Grammatikopoulos (King’s College London, UK) confirmed that odevixibat was associated with a reduction in alanine aminotransferase, aspartate aminotransferase, and total bilirubin after 24 weeks of treatment compared with placebo but that these differences were not significant.
Although there was a “numerically higher incidence” of liver-related TEAEs with odevixibat than placebo, the researchers say that these were judged to be unrelated to treatment and there were no episodes of drug-induced liver injury.
Meanwhile, Alexander Miethke (Cincinnati Children’s Hospital Medical Center, Ohio, USA) presented an analysis of MARCH and MARCH-ON trial data demonstrating that children whose pruritus improved during maralixibat therapy experienced a significant improvement in growth.
Specifically, both the 28 children with the bile salt export pump (BSEP) subtype and the 60 with any form of PFIC who achieved a 1-point or greater decrease in their Itch-Reported Outcome (ItchRO) score or an average score of less than 1 point experienced “sustained, significant improvements” in their height Z-score between baseline and weeks 26 (MARCH) and week 70 (MARCH-ON) compared with nonresponders.
Similar, significantly greater improvements in weight Z-score from baseline were also found among both the BSEP and all-PFIC cohort patients with pruritus response compared with nonresponders.
These “consistent trends” may “indicate a potential disease-modifying effect of maralixibat treatment in PFIC,” Miethke said, suggesting that further research could look at mechanisms for this relationship, such as impact on growth hormone secretion and improvements in “caloric utilization.”
Other updates from the MARCH and MARCH-ON trials indicated better clinically significant event-free survival (EFS) for patients with an sBA response to maralixibat, defined as at least a 75% reduction from baseline or a concentration below 102 or 65 µmol/L for patients with BSEP or FIC1 disease, respectively,
None of the sBA responders with BSEP or FIC1 PFIC experienced liver transplantation, liver decompensation, surgical biliary diversion, or death compared with 13% and 22% of BSEP and FIC1 nonresponders, respectively.
“These data support the importance of sBA reduction in PFIC and the potential of maralixibat to facilitate this biochemical change and improve EFS in patients with PFIC,” say lead author Richard Thompson and colleagues. “While these results are promising, additional time is needed to assess longer-term outcomes.”
Finally, Henkjan Verkade (Beatrix Children’s Hospital University Medical Center, Groningen, the Netherlands) and colleagues presented a poster elucidating the relationship between pruritus response to maralixibat and changes to BA subspecies in 60 PFIC participants of the MARCH and MARCH-ON trials.
Specifically, they identified a significant negative association between unconjugated primary BAs and both ItchRO score and direct bilirubin concentrations, but significant positive correlations between conjugated primary BAs and these endpoints.
There was also a significantly different BA composition in sBA responders compared with nonresponders and placebo-treated children, the authors reported.
“These data help elucidate the pathophysiology of how maralixibat may improve both pruritus and underlying liver health in patients with PFIC,” Verkade et al conclude.
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AASLD The Liver Meeting; San Diego, California, USA: 15–19 November 2024