Madrigal Pharmaceuticals Announces First Patient Dosed in MAESTRO-NAFLD-1, a Second Phase 3 Multi-Center, Double-Blind, Randomized, Placebo-Controlled Study of Resmetirom (MGL-3196) in Patients With Non-Alcoholic Steatohepatitis (NASH) and Presumed NASH (
-- MAESTRO-NAFLD-1 is the second resmetirom Phase 3 clinical trial in patients with
- The primary goals of MAESTRO-NAFLD-1 are to:
- collect additional safety data in resmetirom treated patients with biopsy-confirmed or presumed
NASH ; - further support the broad potential therapeutic benefits of resmetirom on liver and cardiovascular endpoints that were demonstrated in Phase 2 clinical studies; and,
- assess noninvasive lipid, fibrosis and imaging biomarkers to monitor clinical improvement in
NASH patients.
- collect additional safety data in resmetirom treated patients with biopsy-confirmed or presumed
MAESTRO-NAFLD-1 is a 52-week Phase 3, double-blind, placebo-controlled clinical study in 700 patients designed to evaluate the safety and biomarkers in resmetirom as compared with placebo treated patients in a broad segment of patients with
MAESTRO-NAFLD-1 is expected to enroll 700 patients with biopsy-proven or presumed
“The initiation of this second Phase 3 NASH safety and biomarker study is an important next step in establishing the broad therapeutic benefits of resmetirom and its unique potential among NASH drugs in development to decrease cardiovascular risk through the reduction of hepatic fat and multiple atherogenic lipids including LDL-cholesterol,” stated Dr. Rebecca Taub, M.D., Chief Medical Officer and President of R & D of Madrigal. “It is well-established that NAFLD/NASH patients are at significantly increased risk of cardiovascular morbidity and mortality. Based on treatment effects on
Dr. Stephen Harrison, M.D., Principal Investigator of the study, Medical Director for Pinnacle Clinical Research, San Antonio,
“Because the leading cause of death for patients with
About NASH
Non-alcoholic Steatohepatitis (
Patients with NASH are at heightened cardiovascular risk. Patients across the spectrum of non-alcoholic fatty liver disease (NAFLD) die more frequently from cardiovascular events than from their liver disease. Multiple factors may contribute to this risk, including elevated levels of LDL-C and excess liver fat. A significant segment of this large group of patients may also suffer from diabetes and metabolic syndrome, and have lipid levels that are above target despite treatment with established therapies. These patients may benefit from therapy to lower their lipid levels, including excess liver fat.
About Resmetirom (MGL-3196)
Among its many functions in the human body, thyroid hormone, through activation of its beta receptor, plays a central role in controlling lipid metabolism, impacting a range of health parameters from levels of serum cholesterol and triglycerides to the pathological buildup of fat in the liver. Attempts to exploit this pathway for therapeutic purposes in cardio-metabolic and liver diseases have been hampered by the lack of selectivity of older compounds for the thyroid hormone receptor (THR)-β, chemically-related toxicities and undesirable distribution in the body.
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. Madrigal believes that resmetirom is the first orally administered, small-molecule, liver-directed, truly β-selective THR agonist.
Based in part on the positive Phase 2 clinical study results in patients with NASH [see: Madrigal Pharmaceuticals Announces Lancet Publication of Positive Phase 2 Results for resmetirom], in
About the Phase 3 Registration Program for the Treatment of
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 will be fibrosis improvement of at least one stage, with no worsening of NASH, and lowering of LDL-cholesterol.
In the NASH Phase 2 study and a second positive Phase 2 clinical study in patients with heterozygous familial hypercholesterolemia [Madrigal Pharmaceuticals Phase 2 HeFH Results], significant reductions in multiple atherogenic lipids were observed.
A second 52-week Phase 3 multi-center, double-blind, randomized, placebo-controlled study of resmetirom, MAESTRO-NAFLD-1, in 700 patients with non-alcoholic fatty liver disease (NAFLD), presumed
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 Madrigal Pharmaceuticals
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. Such statements contain words such as “expect,” “could,” “may,” “might,” “will,” “be, “predict,” “project,” “intend,” “believe,” “estimate,” "continue," "future,” or the negative thereof or comparable terminology and the use of future dates. Forward-looking statements reflect management's current knowledge, assumptions, judgment and expectations regarding future performance or events. Such forward-looking statements include but are not limited to statements or references concerning: our primary and secondary study endpoints and their achievement potential; optimal dosing levels for resmetirom; projections regarding potential future NASH resolution, fibrosis treatment, cardiovascular effects and lipid treatment; the achievement of enrollment objectives concerning patient number and/or timing; and potential NASH or NAFLD patient risk profile benefits. Although management believes that the expectations reflected in such statements are reasonable, they 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, the company's clinical development of resmetirom, enrollment uncertainties, outcomes or trends from competitive studies, the risks of achieving potential benefits in a study that includes substantially more patients than our prior study, 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 Part I, Item 1A of our Annual Report on Form 10-K for the year ended December 31, 2018, as well as in our other filings with the SEC.
Investor Contact:
Marc Schneebaum, Madrigal Pharmaceuticals, Inc. IR@madrigalpharma.com
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Source: Madrigal Pharmaceuticals, Inc.