- High accuracy in predicting advanced
NASHfibrosis (F2-F3) in Phase 3 MAESTRO- NASHstudy using clinical characteristics and simple, readily available non-invasive imaging and biomarkers
- Data from ongoing MAESTRO-NAFLD-1 open label arm confirm robust liver fat reduction on MRI-PDFF and reduction in liver fibrosis measured on magnetic resonance elastography (MRE) at Week 16 of resmetirom treatment
- Quality of life improvements in resmetirom-treated patients demonstrated in
NASHPhase 2 study
- Dr. Stephen Harrison will present resmetirom data from ongoing Phase 3 MAESTRO studies at AASLD on
Friday November 13, 2020
Madrigal, a Silver Level Sponsor of The Liver Meeting Digital Experience™, is looking forward to Dr. Stephen Harrison’s oral presentation as well as three poster presentations to registered attendees with access via The Liver Meeting Digital Experience™ website, beginning on
Friday, November 13, 2020, from 4:30-5:00 PM ET, Dr. Stephen Harrison, M.D., Medical Director for Pinnacle Clinical Research, San Antonio, Texas, and Visiting Professor of Hepatology, Oxford University, and Principal Investigator of the MAESTRO studies, will make a presentation in Madrigal’s product theater titled: “Resmetirom for the Treatment of NASH: Early Data from the Phase 3 MAESTRO Clinical Trials.”
“We remain confident in achieving the primary and key secondary endpoints in both of our studies. Open label MAESTRO-NAFLD-1 data, using non-invasive measures, predict a favorable probability of demonstrating primary and key secondary liver biopsy and lipid endpoints in the ongoing MAESTRO-
- ALGORITHM FOR PREDICTING ADVANCED
NASHFIBROSIS ON SCREENING BIOPSY IN RESMETIROM PHASE 3 MAESTRO- NASHCLINICAL TRIAL
Dr. Stephen A Harrison1, Dr.
Rebecca A. Taub2, Prof. Morten Asser Karsdal3, John Franc2, Dr. Mustafa R Bashir4, Mr. Jordan Mark Barbone2, Dr. Guy Neff5, Dr. Nadege T Gunn1 and Dr. Sam Moussa6, (1) Pinnacle Clinical Research, (2) Madrigal Pharmaceuticals, (3) Biomarkers & Research, Nordic Bioscience, (4) Department of Radiology, Duke University Medical Center, (5) Covenant Research, LLC, (6) Medical, Adobe Gastroenterology
NASHis a Phase 3 double-blind placebo-controlled serial liver biopsy study to evaluate resmetirom for the treatment of NASHwith F2 or F3 fibrosis and an exploratory F1 arm. Data was assessed for the power of the screening paradigm to predict eligible NASHwith fibrosis on liver biopsy. These data suggest that PRO-C3 is a marker not only of fibrosis stage in NASHbut also of the level of NASHactivity (inflammation and ballooning) in the NASHliver. In the absence of a liver biopsy, elevated PRO-C3 in the setting of metabolic syndrome (or FIBC3 (PRO-C3 [age, BMI, platelets, T2D]), fibroscan and MRI-PDFF may predict advanced NASH.
- TREATMENT WITH RESMETIROM IN PHASE 3 MAESTRO-NAFLD-1
NASHSTUDY OPEN LABEL ARM: EFFECTS ON BIOMARKERS AND IMAGING
Dr. Stephen A Harrison,
Pinnacle Clinical Research, Dr. Naim Alkhouri, Arizona Liver Health, Dr. Rebecca A. Taub, Madrigal Pharmaceuticals, Dr. Guy Neff, Covenant Research, LLC, Dr. Seth J Baum, Excel Medical Clinical Trials and Dr. Mustafa R Bashir, Department of Radiology, Duke University Medical Center
Data from the ongoing Open Label Arm of Madrigal’s MAESTRO-NAFLD-1 trial will be presented.
In this 52 week Phase 3 open label study,
NASHpatients identified using non-invasive imaging and biomarkers were treated with resmetirom 100 mg and demonstrated rapid reduction in hepatic fat, biomarkers and atherogenic lipids after 12-16 weeks of treatment, potentially supporting use of non-invasive tests to monitor individual NASHpatient response to resmetirom treatment.
|Relative % change at Week 16||p- value||MRE, Baseline (>2.9, F1-F3) (kpa)||Change
|Open label cohort||17.6||53%||<0.0001||3.5||-0.34||0.003|
- IMPROVEMENT OF HEALTH-RELATED QUALITY OF LIFE IS ASSOCIATED WITH IMPROVEMENT OF FAT FRACTION BY MRI-PDFF IN PATIENTS WITH NONALCOHOLIC STEATOHEPATITIS TREATED WITH RESMETIROM
Zobair M. Younossi, MD, MPH, FAASLD1, Maria Stepanova2, Dr. Rebecca A. Taub3, Mr. Jordan Mark Barbone3, Dr. Sam Moussa4and Dr. Stephen A Harrison5, (1) Center for Liver Disease, Department of Medicine, Inova Health System, (2) Center for Outcomes Research in Liver Diseases, Washington, DC, United States, (3) Madrigal Pharmaceuticals, (4) Medical, Adobe Gastroenterology, (5) Pinnacle Clinical Research
A review of patient reported outcome data from resmetirom’s Phase 2 NASH study demonstrates that
NASHpatients treated with resmetirom who had liver fat reduction also improved some quality of life measures, particularly physical components such as bodily pain. Ongoing Phase 3 studies will assess long-term sustainability of quality of life improvements with resmetirom treatment.
About Resmetirom (MGL-3196)
Thyroid hormone, through activation of its β-receptor in hepatocytes, plays a central role in liver function impacting a range of health parameters from levels of serum cholesterol and triglycerides to the pathological buildup of fat in the liver. Thyroid hormone receptor (THR)-β action in the liver is key to proper function of the liver, including regulation of mitochondrial activity such as breakdown of liver fat and control of the level of normal, healthy mitochondria. Patients with
To exploit the thyroid hormone receptor (THR)-β pathway for therapeutic purposes in cardio-metabolic and liver diseases, it is important to avoid activity at the THR- receptor, the predominant systemic receptor for thyroid hormone that is responsible for activity outside the liver including in heart and bone. The lack of selectivity of older thyromimetic compounds, chemically-related toxicities and undesirable distribution in the body led to safety concerns. Madrigal recognized that greater selectivity for thyroid hormone receptor (THR)-β and liver targeting might overcome these challenges and deliver the full therapeutic potential of THR-β agonism. Resmetirom has been shown to be highly selective based on 1) THR- β receptor functional selectivity based on both in vitro and in vivo assays 2) specific uptake into the liver, its site of action, virtually avoiding any uptake into tissues outside the liver. In short and long term human and animal studies, resmetirom has been confirmed to be safe and devoid of activity at the THR- receptor and without impact on bone or cardiac parameters. Resmetirom does not impact the thyroid axis hormones, including the central thyroid axis. Madrigal believes that resmetirom is the first orally administered, small-molecule, liver-directed, truly β-selective THR agonist.
About the Phase 3 Registration Program for the Treatment of
Analyses from the resmetirom Phase 2 NASH study demonstrate that the magnitude of liver fat reduction accurately predicts
Madrigal has also reported, including in presentations by
The Phase 3 MAESTRO-
A second 52-week Phase 3 multi-center, double-blind, randomized, placebo-controlled study of resmetirom, MAESTRO-NAFLD-1, was initiated in
These and other data, including safety parameters, form the basis for potential subpart H submission to FDA for accelerated approval for the treatment of
About Resmetirom’s Potential to Confer Cardiovascular Risk Reduction in
Additionally, resmetirom lowers multiple atherogenic lipids, including LDL cholesterol, apolipoprotein B, triglycerides, and lipoprotein (a), as demonstrated in Phase 2, a key differentiating factor compared with other
Because of their diabetes, dyslipidemia, hypertension, obesity in concert with an inflamed, fatty liver,
This communication contains “forward-looking statements” made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, that are based on our beliefs and assumptions and on information currently available to us, but are subject to factors beyond our control. Forward-looking statements include but are not limited to statements or references concerning: our clinical trials; research and development activities; the timing and results associated with the future development of our lead product candidate, MGL-3196 (resmetirom); our primary and secondary study endpoints for resmetirom and the potential for achieving such endpoints and projections; optimal dosing levels for resmetirom; projections regarding potential future
Forward-looking statements are subject to a number of risks and uncertainties including, but not limited to: our clinical development of resmetirom; enrollment uncertainties, generally and in relation to COVID-19 shelter-in-place and social distancing measures and individual precautionary measures that may be implemented or continued for an uncertain period of time; outcomes or trends from competitive studies; the risks of achieving potential benefits in studies that includes substantially more patients than our prior studies; the timing and outcomes of clinical studies of resmetirom; and the uncertainties inherent in clinical testing. Undue reliance should not be placed on forward- looking statements, which speak only as of the date they are made. Madrigal undertakes no obligation to update any forward-looking statements to reflect new information, events or circumstances after the date they are made, or to reflect the occurrence of unanticipated events. Please refer to Madrigal's filings with the
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Source: Madrigal Pharmaceuticals, Inc.