1777-P: Early Real-World Liver Biomarker Changes among Resmetirom-Treated MASH Patients, with and without T2DM: A Descriptive Cohort Study

Introduction and Objective: Resmetirom is a THR-β agonist conditionally FDA-approved for noncirrhotic MASH with moderate-to-advanced fibrosis. As T2DM is common in MASH patients, we assessed early mean changes in liver biomarkers by T2DM status in resmetirom-treated adults. Methods: A retrospective, descriptive cohort study using Latica real-world data repository included adults with ≥1 resmetirom prescription (Apr 2024-2025; index date=first prescription) and ≥6 months follow-up, excluding those with end-stage liver disease 2 years pre-index. Patients were stratified by baseline T2DM. Outcomes included changes in liver enzymes, metabolic measures, and non-invasive fibrosis markers (FAST score, Liver Stiffness Measurement [LSM], Controlled Attenuation Parameter [CAP]). Responder endpoints were defined as FAST reduction ≥0.22, ALT reduction ≥17 U/L or ≥20%, and LSM reduction ≥30%. Results: The cohort included 712 patients; 411 (57.7%) hadT2DM, of which >70% had ≥2 additional comorbidities. Mean treatment duration was 5.7 months. In the entire cohort, resmetirom was associated with mean improvements in liver enzymes (ALT −13.6U/L [n=330], AST −8.5 U/L [n=322]), metabolic measures (LDL −12.8 mg/dL [n=19], triglycerides −65 mg/dL [n=24], BMI −0.68 kg/m2 [n=503]), and non-invasive fibrosis markers (FAST −0.18 [n=28], LSM −2.2 kPa [n=70], CAP −42.6dB/m [n=45]). Biomarker reductions were similar between T2DM and non-T2DMgroups (ALT −13.4 [n=206] vs −14.0 U/L [n=124]; AST −8.2 [n=199] vs −9.0 U/L[n=123]; BMI −0.8 [n=306] vs −0.5 kg/m2 [n=197]), but CAP improved more in patients without T2DM (CAP −34.9 [n=31] vs −59.9 dB/m [n=14]). Responder rates (%) were comparable in T2DM and non-T2DM groups for LSM (44.9 vs 33.3)and ALT (45.6 vs 48.4), but lower for FAST (35.0 vs 62.5). Conclusion: This descriptive analysis showed mean improvements in liver biomarkers and non-invasive tests over ~6 months of resmetirom therapy, with broadly similar patterns regardless of T2DM status. Disclosure Y. Kim: Employee; Current; Madrigal Pharmaceuticals, Inc. Stock/Shareholder; Current; Madrigal Pharmaceuticals, Inc. N. Alkhouri: Advisory Panel; Current; Madrigal Pharmaceuticals, Inc. Speaker's Bureau; Current; Madrigal Pharmaceuticals, Inc. Research Support; Current; Madrigal Pharmaceuticals, Inc. Advisory Panel; Current; Novo Nordisk. Speaker's Bureau; Current; Novo Nordisk. Research Support; Current; Novo Nordisk. J. O'Donnell: Employee; Current; Madrigal Pharmaceuticals, Inc. Stock/Shareholder; Current; Madrigal Pharmaceuticals, Inc. K.M. Johnston: None. R. Mustafa: None. Y. Silberberg: Other - Employees of Latica, which received funds from Madrigal Pharmaceuticals for this work.; Current; Madrigal Pharmaceuticals, Inc.