Madrigal Pharmaceuticals, Inc. (NASDAQ:MDGL) announced today that
on Friday, August 28, 2020 at the Digital International Liver
Congress
™ 2020, European Association for the Study
of the Liver (EASL), secondary analyses of data from its Phase 2
NASH study with MGL-3196 (resmetirom) will be presented. Resmetirom
is currently in Phase 3 development for the treatment of NASH
patients with stage 2-3 fibrosis (ClinicalTrials.gov NCT03900429
and ClinicalTrials.gov/NCT04197479).
Rohit Loomba, MD, MHSc, Professor of Medicine (with tenure),
Division of Gastroenterology, Department of Medicine, and
Director, NAFLD Research Center and Director, Liver Epidemiology
Training Program, University of California at San Diego, will
present “Magnetic resonance imaging-proton density fat fraction
(MRI-PDFF) to predict treatment response on NASH liver biopsy: a
secondary analysis of the resmetirom randomised placebo-controlled
phase 2 clinical trial” (AS077), during the Abstract session: NAFLD
- Pharmacological Therapy, on Friday, August 28, 2020, at 12:00 PM
CET (6:00 AM EDT). Registered attendees will be able to watch
the live presentation on the Digital ILC 2020 website, Channel
3.
Dr. Loomba commented, “MRI-PDFF reduction has been shown to be
associated with improvement in NASH components as assessed on liver
biopsy. These secondary analyses of Madrigal’s Phase 2 NASH
clinical trial add significant additional insight into the
potential of PDFF to predict NASH response. These findings support
the pathogenicity of liver steatosis in NASH and fibrosis
progression.“
Madrigal is excited to host four presentations by NASH experts,
Impacting NASH: Focus on Liver and Cardiovascular Benefits, that
registered attendees will be able to access via the Madrigal
virtual booth on the Digital ILC 2020 website, on Friday, August
28, 2020, beginning at 1:00 PM CET. The presentations will
also be available via the Newsroom-Webcasts page on Madrigal’s
website beginning at the same time:
- “Epidemiology of NASH: CV- and Liver-related Outcomes”Zobair
Younossi, MD, MPH, FACP, FACG, AGAFChairman, Department of
Medicine, Inova Fairfax Medical Campus. He is also Professor of
Medicine, Virginia Commonwealth University, Inova Campus and
Affiliate Professor of Biomedical Sciences at George Mason
University.
- Dr. Younossi focuses on global prevalence and trends in
NAFLD/NASH, including the comprehensive burden of clinical,
economic, and quality of life factors associated with the
disease.
- “Resmetirom for the Treatment of NASH”Stephen A. Harrison,
MDVisiting Professor of Hepatology, Radcliffe Department of
Medicine, University of Oxford, Oxford, England and Medical
Director Pinnacle Clinical Research San Antonio, TX
- Dr. Harrison discusses the non-invasive and clinical
identification of patients at high risk for NASH with fibrosis,
highlighting findings from the resmetirom clinical trial
program.
- “Real-life Treatment of NASH: Non-invasive Imaging in NASH
Diagnosis and Treatment. Magnetic resonance imaging-proton density
fat fraction (MRI-PDFF) to Predict Benefit in Patients with NASH:
Focus on Resmetirom”Rohit Loomba, MD, MHScProfessor of Medicine
(with tenure), Division of Gastroenterology, Department of
Medicine, and Director, NAFLD Research Center and Director, Liver
Epidemiology Training Program, University of California at San
Diego
- Dr. Loomba provides an overview of MRI-PDFF as a non-invasive
diagnostic for NASH and discusses findings from a secondary
analysis of the resmetirom Phase 2 study that examine MRI-PDFF
response as a predictor of histologic response in patients with
NASH.
- “The Intersection of CVD and NASH, the Next CVD Prevention
Frontier”Seth Baum, MD, FACC, FACPM, FAHA, FNLA,FASPCFounder and
CEO, Excel Medical Clinical Trials, and Clinical Affiliate
Professor of Medicine at Florida Atlantic University (FAU) Medical
School in Boca Raton, FL
- Dr. Baum highlights topics of dyslipidemia, carotid-artery
intimal medial thickness (CIMT), coronary artery calcification
(CAC), and cardiovascular mortality in NAFLD/NASH, in addition to
the role of resmetirom as experts consider cardiovascular disease
in the NASH treatment landscape.
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 NASH have reduced levels of thyroid
hormone activity in the liver with resultant impaired hepatic
function, in part due to the inflamed state of the liver that
causes degradation of thyroid hormone.
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-α 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-α 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 NASH (Non-alcoholic steatohepatitis)Analyses from the
resmetirom Phase 2 NASH study demonstrate that the magnitude of
liver fat reduction accurately predicts NASH resolution and liver
fibrosis reduction and, specifically, that the resmetirom doses
being used in Madrigal’s Phase 3 MAESTRO-NASH trial could achieve
the level of fat reduction predictive of NASH resolution and
fibrosis reduction [Madrigal COVID and ABSTRACT Press
Release_20200414].
The Phase 3 MAESTRO-NASH trial is expected to enroll 900
patients with biopsy-proven NASH (fibrosis stage 2 or 3),
randomized 1:1:1 to receive resmetirom 80 mg once a day, 100 mg
once a day, or placebo. After 52 weeks of treatment a second biopsy
is performed. The primary surrogate endpoint on biopsy will
be NASH resolution, with at least a 2-point reduction in
NAS (NASH Activity Score), and with no worsening of fibrosis. Two
key secondary endpoints are liver fibrosis improvement of at least
one stage, with no worsening of NASH, and lowering of
LDL-cholesterol [ClinicalTrials.gov/NCT03900429].
A second 52-week Phase 3 multi-center, double-blind, randomized,
placebo-controlled study of resmetirom, MAESTRO-NAFLD-1, was
initiated in December 2019 in 700 patients with non-alcoholic fatty
liver disease (NAFLD), presumed NASH, randomized 1:1:1 to receive
resmetirom 80 mg once a day, 100 mg once a day, or placebo.
MAESTRO-NAFLD-1 also includes a 100 mg resmetirom open label arm in
up to 100 patients. Unlike MAESTRO-NASH, MAESTRO-NAFLD-1 is a
non-biopsy study and represents a “real-life” NASH study. NASH or
presumed NASH is documented using historical liver biopsy or
non-invasive techniques including fibroscan and MRI-PDFF. Using
non-invasive measures, MAESTRO-NAFLD-1 is designed to provide
incremental safety information to support the NASH indication as
well as provide additional data regarding clinically relevant key
secondary efficacy endpoints to better characterize the potential
clinical benefits of resmetirom on cardiovascular and liver related
endpoints. These key secondary endpoints include LDL-cholesterol,
apolipoprotein B and triglyceride (TG) lowering; reduction of liver
fat as determined by magnetic resonance imaging, proton density fat
fraction (MRI-PDFF); and reduction of PRO-C3, a NASH fibrosis
biomarker. [ClinicalTrials.gov/NCT04197479] Additional
secondary and exploratory endpoints will be assessed including
reduction in liver enzymes, fibroscan scores and other fibrosis and
inflammatory biomarkers.
These and other data, including safety parameters, form the
basis for potential subpart H submission to FDA for
accelerated approval for the treatment of NASH. The original 900
patients in the MAESTRO-NASH study will continue on therapy after
the initial 52-week treatment period; up to another 1,100 patients
are to be added using the same randomization plan and the study is
expected to continue for up to 54 months to accrue and measure
clinical events, most relevantly progression to
cirrhosis.
About Resmetirom’s Potential to Confer Cardiovascular
Risk Reduction in NASH patientsAdditionally, 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 NASH therapeutics. The magnitude of reduction of these lipids
support a potential indication for treatment of hyperlipidemia in
NASH patients and predicts a potential for benefit on
cardiovascular (CV) events in NASH patients who die most frequently
of CV, not liver disease.
Because of their diabetes, dyslipidemia, hypertension, obesity
in concert with an inflamed, fatty liver, NASH patients,
particularly those with advanced fibrosis, are at a substantially
increased CV risk compared to the general population. Resmetirom’s
ability to decrease liver fat, which is an independent risk factor
for CV events, and resmetirom’s effect to reduce atherogenic lipids
are being further evaluated in several key secondary endpoints in
both MAESTRO Phase 3 clinical studies.
About Madrigal Pharmaceuticals Madrigal
Pharmaceuticals, Inc. (Nasdaq: MDGL) is a clinical-stage
biopharmaceutical company pursuing novel therapeutics that target a
specific thyroid hormone receptor pathway in the liver, which is a
key regulatory mechanism common to a spectrum of cardio-metabolic
and fatty liver diseases with high unmet medical need. Madrigal’s
lead candidate, resmetirom, is a first-in- class, orally
administered, small-molecule, liver-directed, thyroid hormone
receptor (THR)-β selective agonist that is in currently in two
Phase 3 clinical studies, MAESTRO-NASH and MAESTRO-NAGLD-1,
designed to demonstrate multiple benefits across a broad spectrum
of NASH (non-alcoholic steatohepatitis) and NAFLD (non-alcoholic
fatty liver disease) patients. For more information, visit
www.madrigalpharma.com.
Forward-Looking Statements 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 NASH resolution, safety,
fibrosis treatment, cardiovascular effects, lipid treatment or
biomarker effects with resmetirom; the predictive power of liver
fat reduction on NASH resolution with fibrosis reduction or
improvement; the achievement of enrollment objectives concerning
patient number, safety database and/or timing for our studies;
potential NASH or NAFLD patient risk profile benefits with
resmetirom; and our possible or assumed future results of
operations and expenses, business strategies and plans, capital
needs and financing plans, trends, market sizing, competitive
position, industry environment and potential growth opportunities,
among other things. Forward-looking statements: reflect
management’s current knowledge, assumptions, judgment and
expectations regarding future performance or events; include all
statements that are not historical facts; and can be identified by
terms such as “anticipates,” “be,” “believes,” “continue,” “could,”
“demonstrates,” ”design,” “estimates,” “expects,”
“forecasts,” “future,” “goal,” “hopeful,” “intends,” “may,”
“might,” “plans,” “potential,” “predicts,” ”predictive,”
“projects,” “seeks,” “should,” “will,” “would” or similar
expressions and the negatives of those terms. Although
management presently believes that the expectations reflected in
such forward-looking statements are reasonable, it can give no
assurance that such expectations will prove to be correct and you
should be aware that actual results could differ materially from
those contained in the forward-looking statements.
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 U.S. Securities and Exchange Commission for more
detailed information regarding these risks and uncertainties and
other factors that may cause actual results to differ materially
from those expressed or implied. We specifically discuss these
risks and uncertainties in greater detail in the section entitled
"Risk Factors" in our Annual Report on Form 10-K for the year ended
December 31, 2019 and our Quarterly Report on Form 10-Q for the
period ended June 30, 2020, as well as in our other filings with
the SEC.
Investor Contact: Marc Schneebaum, Madrigal
Pharmaceuticals, Inc. IR@madrigalpharma.com
Media Contact: Mike Beyer, Sam Brown Inc.
mikebeyer@sambrown.com 312 961 2502
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