OC22 Long-term maintenance of response and improved liver heath with maralixibat in patients with progressive familial intrahepatic cholestasis (PFIC): 2-year data from the MARCH-ON study
Bibliographic record
Abstract
Progressive familial intrahepatic cholestasis (PFIC) is a group of genetic disorders resulting in disrupted bile composition, cholestasis, and pruritus. Maralixibat, an inhibitor of the ileal bile acid transporter, is approved in the EU for the treatment of Progressive Familial Intrahepatic Cholestasis (PFIC) in individuals ≥3 months of age. In the 26-week placebo-controlled MARCH Phase 3 study, MRX at 570 μg/kg BID demonstrated significant improvements in pruritus, serum bile acids (sBA), total bilirubin (TB) and growth in patients across the broadest range of PFIC types studied to date. We report on long-term maintenance of effect of up to 2 years of treatment with MRX in MARCH-ON, an open-label, long-term extension study of MARCH. Long-term maintenance of response was assessed for patients who were originally randomized to receive MRX in MARCH and continued with treatment in MARCH-ON (MRX-MRX group: n=47), and for patients who received placebo (PBO) in the MARCH study and switched to open-label MRX in MARCH-ON (PBO-MRX group: n=41). Assessments included: pruritus, sBA, TB, growth z-scores, and incidence of treatment-emergent adverse events (TEAEs). Baseline (BL) was defined as the start of MRX for each group. For the MRX-MRX group, the median (min, max) time on MRX was 638 days (10, 1135). 13 of 47 patients reached Week 104 at time of analysis. Significant improvements observed in the first 26 weeks of the MARCH study were sustained through Week 104 in MARCH-ON for pruritus (-2.03, p<0.0001), sBA (-166 μmol/L, p=0.003), TB (-27.7 μmol/L, p=0.02), and growth (height z-score: +0.40, p=0.046; weight z-score: +0.52, p=0.01). In the PBO-MRX group, the median time on MRX was 456 days (22, 720). 18 of 41 patients reached Week 52 of MRX treatment at time of analysis. Significant improvements through Week 52 for pruritus (-1.1, p=0.0001), sBA (-71 μmol/L, p=0.03), and growth (height z-score: +0.37, p=0.01; weight z-score: +0.32, p=0.03) were in line with observations from the initial MARCH MRX group. Additionally, numeric reductions in TB (-6.4 μmol/L; p=0.7) were observed. No new safety signals were identified. The most common TEAEs were GI-related with diarrhea (50%) being mostly mild and transient. Significant and sustained improvements in pruritus, sBA, TB, and growth are observed with up to 2 years of MRX treatment across the broadest range of genetic PFIC types studied to date. These data suggest overall improved liver health with MRX treatment which can be maintained long-term.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".