Z Gastroenterol 2023; 61(01): e26
DOI: 10.1055/s-0042-1759975
Abstracts | GASL
Poster Visit Session lll Metabolism (incl. NAFLD) 27/01/2023, 16.20 pm – 16.55 pm

Biomarkers, Imaging, and Safety in a Well-compensated NASH Cirrhotic Cohort Treated With Resmetirom, a Thyroid Hormone Receptor-beta Selective Agonist, for 52 Weeks

Jörn Schattenberg
1   Metabolic Liver Research Program, I. Department of Medicine, University Medical Center, Mainz
,
KrisV. Kowdley
2   Liver Institute Northwest, Seattle, WA, USA
,
Rebecca A. Taub
3   Madrigal Pharmaceuticals, Conshohocken, PA, USA
,
Naim Alkhouri
4   Arizona Liver Health, Tucson, AZ, USA
,
Guy W. Neff
5   Covenant Metabolic Specialists, Sarasota, FL, USA
,
Stephen A. Harrison
6   University of Oxford, UK & Pinnacle Clinical Research, San Antonio, TX, USA
› Author Affiliations
 
 

    MAESTRO-NAFLD-1 is a randomized, double-blind, placebo-controlled Phase 3 trial evaluating resmetirom, a thyroid hormone receptor-beta selective agonist, in NASH patients identified using noninvasive biomarkers and imaging (NCT04197479). MAESTRO-NAFLD-1 includes an open-label resmetirom arm in well-compensated NASH cirrhotic patients. Eligibility required≥3 metabolic risk factors and NASH cirrhosis (diagnosed by biopsy or accepted criteria). Primary and key secondary endpoints include safety, relative percent reduction in MRI-PDFF (Week 16), LDL-C, apoB, and triglycerides (Week 24), and fibrosis markers. All patients received 80 or 100mg resmetirom daily for 52 weeks. Cohort 1 (n=105) has completed 52 weeks of treatment. Cirrhosis stage inversely correlated with baseline MRI-PDFF. At Week 52, resmetirom reduced FibroScan CAP by 42dB/m (p<0.0001) and FibroScan VCTE (LSM) by 7.6kPa (p=0.02). In patients with baseline MRI-PDFF>5% (5%=ULN), resmetirom reduced MRI-PDFF by 37% (p<0.0057). At Week 52, resmetirom reduced MRE by 0.68kPa; 34% of patients achieved an MRE reduction≥15%. GGT and ALP were reduced with resmetirom (by 27% and 18%, respectively; p=0.04 for both). Liver volume, which was elevated at baseline, was reduced by 15.9% at Week 16 (p<0.0001), independent of baseline MRI-PDFF. Liver volume reduction correlated with reduction in MRE, MRI-PDFF, TIMP, P3NP, and SHBG. Resmetirom reduced LDL-C (20%), apoB (20%), triglycerides (21%), and Lp(a) (30%), independent of cirrhosis stage. Resmetirom was well tolerated. BP decreased by 4-5mmHg. Overall, resmetirom reduced markers of cardiovascular risk and fibrosis in NASH cirrhotic patients.


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    Publication History

    Article published online:
    18 January 2023

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