Primary Results From MAESTRO-NASH:
A Pivotal Phase 3 52-week Serial Liver Biopsy Study
in 966 Patients With NASH & Fibrosis
Stephen A. Harrison,1 Pierre Bedossa,2 Cynthia D. Guy,3 Jörn M. Schattenberg,4 Rohit Loomba,5 Rebecca Taub,6 Dominic Labriola,6 Sam E. Moussa,7 Guy W. Neff,8 Arun J. Sanyal,9 Mazen Noureddin,10 Meena Bansal,11 Naim Alkhouri,12 Vlad Ratziu13
1University of Oxford, Oxford, UK & Pinnacle Clinical Research, San Antonio, TX, USA; 2Translational & Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK; 3Duke University Medical Center, Durham, NC, USA; 4University Medical Center, Mainz, Germany; 5University of California San Diego, La Jolla, CA, USA; 6Madrigal Pharmaceuticals, Conshohocken, PA, USA; 7University of Arizona for Medical Sciences, Tucson, AZ, USA; 8Covenant Metabolic Specialists, Sarasota, FL, USA;
9Virginia Commonwealth University, Richmond, VA, USA; 10Houston Research Institute, Houston, TX, USA; 11Mt Sinai, New York, NY, USA; 12Arizona Liver Health, Tucson, AZ, USA; 13Pitie-Salpetriere Hospital, Institute of Cardiometabolism & Nutrition, Sorbonne Universite, Paris, France.
Presented at The International Liver Congress; 21-24 June 2023; Vienna, Austria.
Disclosures
DISCLOSURES: I disclose the following financial relationship(s) with a commercial interest:
- Scientific advisor or consultant for Akero, Aligos, Altimmune, Arrowhead, Bluejay Therapeutics, Boxer Capital, Chronwell, Echosens, Enyo, Foresite Labs, Galectin, Galecto, Gilead, GSK, Hepagene, Hepion, Hepta Bio, HistoIndex, Humana, Intercept, Ionis, Madrigal, Medpace, NeuroBo Pharmaceuticals, Northsea, Novo Nordisk, Perspectum, Pfizer, Sonic Incytes, Sagimet, Terns, Viking.
- Stock options: Akero, Chronwell, Cirius, Galectin, Genfit, Hepion, Hepta Bio, HistoIndex, Metacrine, NGM Bio, Northsea, Sonic Incytes
- Grant/Research support: Akero, Altimmune, Axcella, BMS, Corcept, Cymabay, Enyo, Galectin, Genentech, Genfit, Gilead, GSK, Hepion, Hightide, Immuron, Intercept, Inventiva, Ionis, Madrigal, NGM Bio, Novartis, Novo Nordisk, Northsea, Pfizer, Poxel, Sagimet, Terns, Viking.
Resmetirom
- Resmetirom is an oral, liver-targetedTHR-βselective agonist in development for NASH1
- In patients with NASH, selectivity for THR-β may provide metabolic benefits of thyroid hormone that are mediated by the liver (reduction of excess hepatic fat & atherogenic lipids/lipoproteins), while avoiding negative systemic effects of excess thyroid hormone in heart & bone
- In the randomized, double-blind,placebo-controlled Phase 2 serial liver biopsy trial in adults with biopsy- confirmed NASH (NCT02912260), resmetirom treatment resolved NASH in a significantly greater percentage of patients & reduced liver enzymes, inflammatory biomarkers, & fibrosis compared with placebo2
- MAESTRO-NASHis a randomized, double-blind,placebo-controlled Phase 3 serial liver biopsy trial evaluating the efficacy & safety of resmetirom in adults with biopsy-confirmed NASH (NCT03900429)
Here we report Week 52 data in 966 patients with NASH & F1B, F2, or F3 fibrosis from the MAESTRO-NASH trial
1. Kelly MJ, et al. J Med Chem. 2014;57(10):3912-3923. 2. Harrison SA, et al. Lancet. 2019;394(10213):2012-2024
.
NASH, nonalcoholic steatohepatitis; THR, thyroid hormone receptor. | 3 |
MAESTRO-NASH Trial Design
KEY ELIGIBILITY CRITERIA
Presence of ≥3 metabolic risk factors
NASH on biopsy: NAS ≥4
(with ≥1 in each component) Fibrosis stage F1B, F2, or F3 ≥8% hepatic fat by MRI-PDFF
MAESTRO-NASH
1:1:1 | Randomization |
Placebo |
Resmetirom 100 mg |
Resmetirom 80 mg |
Liver Biopsy | Screening | D1 |
MRI-PDFF/MRE | ||
LDL-C/Biomarkers | ||
VCTE/CAP |
W16 | W24 | W52 | Month 54 |
52 Week | 54 Month Outcome | ||
Primary Endpoint | Primary Endpoint |
DUAL PRIMARY
ENDPOINT
AT WEEK 52
NASH resolution (ballooning score=0, inflammation score=0/1, & ≥2-point reduction in NAS) with no worsening of fibrosis
≥1-stage improvement in fibrosis with no
worsening of NAS
LDL-C,low-density lipoprotein cholesterol; MRI-PDFF, magnetic resonance imaging-proton density fat fraction; NAS, nonalcoholic fatty liver disease activity score; NASH, nonalcoholic steatohepatitis. | 4 | |
Demographic & Baseline Characteristics (Primary Analysis Population n=966)
Resmetirom 80mg | Resmetirom 100mg | Placebo | ||||||
(n=322) | (n=323) | (n=321) | ||||||
Age, years | 55.9 (11.5) | 57.0 (10.8) | 57.1 (10.5) | |||||
Sex, male | 140 | (43.5) | 141 | (43.7) | 143 | (44.5) | ||
Race, White | 291 (90.4%) | 291 (90.1%) | 281 (87.5%) | |||||
Ethnicity, Hispanic or Latino | 71 (22.0%) | 81 (25.1%) | 52 (16.2%) | |||||
Body mass index | 35.5 (6.4) | 36.2 (7.4) | 35.3 (6.5) | |||||
Type 2 diabetes | 224 | (69.6) | 213 | (65.9) | 210 | (65.4) | ||
Hypertension | 243 | (75.5) | 254 | (78.6) | 257 | (80.1) | ||
Dyslipidemia | 230 | (71.4) | 236 | (73.1) | 224 | (69.8) | ||
Hypothyroidism* | 39 (12.1) | 46 (14.2) | 45 (14.0) | |||||
FibroScan VCTE/LSM, kPa | 13.3 (6.8) | 13.6 (7.1) | 12.9 (5.5) | |||||
FibroScan CAP, dB/m | 346.1 (37.2) | 349.4 (38.7) | 347.2 (37.0) | |||||
MRI-PDFF, % fat fraction | 18.2 (6.8) | 17.2 (6.6) | 17.8 (6.8) | |||||
MRE, kPa | 3.5 (0.9) | 3.7 (1.1) | 3.5 (1.0) | |||||
Baseline medications | ||||||||
GLP-1 RA | 54 (16.8) | 41 (12.7) | 42 (13.1) | |||||
Statin | 149 | (46.3) | 166 | (51.4) | 157 | (48.9) | ||
Baseline liver biopsy | ||||||||
NAS ≥5 | 266 | (82.6) | 288 | (89.2) | 253 | (78.8) | ||
Fibrosis 1B | 16 | (5.0) | 15 | (4.6) | 18 | (5.6) | ||
Fibrosis 2 | 107 | (33.2) | 100 | (31.0) | 112 | (34.9) | ||
Fibrosis 3 | 194 | (60.2) | 203 | (62.8) | 186 | (57.9) | ||
Data are mean (SD) or n (%)
*Patients on thyroxine replacement therapy at screening.
CAP, controlled attenuation parameter; GLP-1 RA, glucagon-likepeptide-1 receptor agonist; LSM, liver stiffness measurement; mITT, modified intent-to-treat; MRE, magnetic resonance elastography; MRI-PDFF, magnetic resonance imaging-proton density fat fraction; NAS, nonalcoholic fatty liver disease activity score; SD, standard deviation; VCTE, vibration-controlled transient elastography.
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Madrigal Pharmaceuticals Inc. published this content on 22 June 2023 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 22 June 2023 13:24:09 UTC.