CHAMGAP
APPROVEDReviewed and approved by the Chamgap Editorial Team (2026-07-24). The draft was written by AI, the existence of all 2 cited sources was verified at the original page, and the verdict passed blind grading and adversarial audit. Methodology v0.6.
Verdict No. 1625 · Search date 2026-07-24 · Methodology v0.6

Maralixibat,
does it really help with Relief of cholestatic pruritus in children with Alagille syndrome?

30-Second Summary
D
Evidence Grade D · 38 · Safety unknown
Pruritus may improve, but the evidence is very small and conflicts with an earlier trial
What the
research shows
Maralixibat is rated D. ICONIC enrolled 31 patients and 29 entered withdrawal after 18 weeks of open-label treatment, but the official modified intention-to-treat primary analysis included only 15 selected bile-acid responders, 5 on maralixibat and 10 on placebo. There was no washout, the primary endpoint was serum bile acid rather than pruritus, and two earlier controlled trials missed their primary endpoints, yielding D with 38 points.
What the
ads claim
Reduced serum bile acids or pruritus must not be expanded into cure, avoidance of transplantation, or longer survival. The small withdrawal design and conflicting evidence must accompany the symptom claim.
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Useful facts when choosing a product

  • Maralixibat is an oral prescription ileal bile acid transporter inhibitor used for cholestatic pruritus in Alagille syndrome.
  • The oral solution is titrated by age and weight; the current label and specialist instructions determine the exact dose.
  • Diarrhea, abdominal pain, vomiting, and liver-test abnormalities can occur and require follow-up.
  • Deficiency of fat-soluble vitamins A, D, E, and K can worsen, so levels and INR are monitored before and during treatment.
Gap Measurement · Verdict 1625 · D 38
What advertising claims
What independent, higher-quality research supports
△ GAP
01

What the research actually shows

ICONIC enrolled 31 patients for 18 weeks of open-label treatment and 29 entered the four-week withdrawal phase, but the official modified intention-to-treat primary analysis included only 15 open-label bile-acid responders, 5 on maralixibat and 10 on placebo. There was no washout. The primary endpoint was the surrogate serum bile acid, not pruritus. Two earlier controlled trials missed their primary endpoints, and clinical-event benefit remains unproven.

02

Why this is classified as D (38)

The no-washout withdrawal analysis included only 15 selected open-label responders and used a surrogate primary endpoint; with two earlier controlled trials missing their primary endpoints, it cannot reverse the prior failures and yields D with 38 points.

Counterpoint. The difficulty of running large independent rare-disease trials does not remove uncertainty.

Rejudgment record. Cross-check applied — Accepted the patient-important pruritus signal but applied rule ①-ⓒ because of a small withdrawal trial and a conflicting earlier failed primary analysis

Sub-claim grades by effect

This ingredient is marketed for several effects. A single overall grade blends strong and weak claims together, so each effect is graded separately here. The overall grade reflects the strongest disconfirming or core claim.

Effect (sub-claim)GradeBasis
Relief of cholestatic pruritusDPruritus is a treatment target, but the official primary analysis included only 15 selected responders and conflicts with two earlier controlled trials that missed their primary endpoints.
Reduced serum bile acidsDThis withdrawal analysis included 15 selected open-label bile-acid responders, and serum bile acid is a surrogate.
Improved clinical events such as avoidance of liver transplantation?This has not been demonstrated in randomized trials.

Cross-check — Codex and Claude

This verdict was drafted by Codex through literature review and source-existence checks, cross-checked through blind grading and adversarial audit, and settled by reapplying the methodology boundary rules. Cases with split grades were resolved through rejudgment.
03

Evidence Table

StudyDesignSampleFundingEndpointResultWeight
Gonzales E et al. 2021 ICONICPeer-reviewed original phase 2b placebo-controlled randomized-withdrawal study with open-label extension10Mirum PharmaceuticalsPrimary: serum bile acid change during four-week withdrawal among bile acid respondersPrimary endpoint met; LS mean difference −117 μmol/L. Pruritus was a positive secondary symptom endpoint.Pivotal small withdrawal study
Shneider BL et al.; Childhood Liver Disease Research Network. 2018 ITCHPeer-reviewed original double-blind randomized placebo-controlled trial37Lumena Pharmaceuticals, an NIH network, and othersPrimary: change in ItchRO at week 13The first prespecified primary analysis failed; difference −0.47 (95% CI −1.14 to 0.20), p=0.16.Conflicting direct randomized evidence
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Receipt — 2 References

All 2 cited sources were verified for existence at the original page (as of 2026-07-24).

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. PMID: 34755627. DOI: 10.1016/S0140-6736(21)01256-3.
checked
Shneider BL, Spino C, Kamath BM, et al.; Childhood Liver Disease Research Network. Placebo-Controlled Randomized Trial of an Intestinal Bile Salt Transport Inhibitor for Pruritus in Alagille Syndrome. Hepatol Commun. 2018;2(10):1184-1198. PMID: 30288474. PMCID: PMC6156750. DOI: 10.1002/hep4.1244.
checked
Draft and rewrite: Codex (AI) · Verification: Codex blind grading and adversarial audit · Final adjudication: Claude
Reviewed and approved: Chamgap Editorial Team · Approval date: 2026-07-24 · Corrections: none

Cite this verdict

Maralixibat x relief of cholestatic pruritus in children with Alagille syndrome Evidence Grade D card
[Chamgap] Maralixibat x relief of cholestatic pruritus in children with Alagille syndrome — Evidence Grade D·38. 2 cited sources checked. Source: https://chamgap.com/en/verdicts/liver/maralixibat-alagille-syndrome-cholestatic-pruritus/ · CC BY 4.0

CC BY 4.0 — free to use with attribution; do not distort grades, numbers, or verdict meaning.

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What this document does and does not do

Chamgap is an information source. It reports what research has and has not confirmed; it does not tell readers what to take or buy. That decision belongs to readers and, when needed, medical or legal professionals. This verdict reflects literature available up to the search date and may change as new research appears. Nothing here is medical advice.