-- Statistically significant improvement in the relative decrease in liver fat in patients treated with MGL-3196 compared with placebo, determined by magnetic resonance imaging-estimated proton density fat fraction (MRI-PDFF) at 12-weeks, the primary end point in this Phase 2 proof-of-concept trial–
-- Statistically significantly more MGL-3196 than placebo treated patients achieved clinically relevant (at least 30%) liver fat reduction at 12 weeks relative to baseline MRI-PDFF–
-- Statistically significant improvements in drug-treatment group compared to placebo in low-density lipoprotein cholesterol (LDL-C), triglycerides and lipoprotein (a) (Lp(a)); these lipids when elevated are associated with increased cardiovascular risk–
-- Statistically significant improvements in liver enzymes in drug-treatment group, with very good all subject tolerability, few serious adverse events, none related to MGL-3196–
-- Clinical trial continues blinded with potential for correlating improvement in non-invasive imaging test (MRI-PDFF at 12 and 36 weeks) with improvement in repeat liver biopsy obtained at 36 weeks–
- Conference call scheduled for
|ALL MGL-3196||HIGH MGL-3196**||Placebo|
|Numbers of patients||78||44||38|
|Relative change in MRI-PDFF (% change from baseline, median)
Significance relative to placebo
|Percentage of patients attaining ≥30% liver fat reduction
Significance relative to placebo
**Prespecified group of patients (44/78) with relatively higher MGL-3196 drug levels
Statistically significant reductions in ALT and AST were observed in MGL-3196 treated patients; greater reductions in ALT and AST, statistically significant relative to placebo, were observed in the prespecified group of 44/78 patients with relatively higher MGL-3196 drug levels. In drug-treated relative to placebo patients, statistically significant improvements were also seen in multiple secondary endpoints considered to be potentially clinically relevant in patients with
MGL-3196 has been well-tolerated with mostly mild AEs, and a few moderate AEs, the numbers of which are balanced between placebo and drug-treatment groups. There are no adverse effects of MGL-3196 on safety laboratory or vital sign parameters. There have been three serious adverse effects in the study, all considered unrelated to MGL-3196.
The on-going study remains blinded. Safety, efficacy of
“NASH is a common liver disease in
Conference Call and Webcast Information
Madrigal will hold a conference call and webcast this morning at
The conference call will also be webcast live and can be accessed at http://www.madrigalpharma.com/newsroom/presentations/ in the “Events and Presentations” section of the Madrigal website.
If you are unable to participate, a replay of the conference call will be available on the website under http://www.madrigalpharma.com/newsroom/presentations/.
About the Phase 2 NASH Study
The randomized, double-blind, placebo-controlled, multi-center Phase 2 study enrolled 125 patients 18 years of age and older with liver biopsy-confirmed
The primary endpoint of the study is the reduction of liver fat at 12 weeks compared with baseline (relative change), assessed by MRI-PDFF, with efficacy confirmed at the end of the trial (36 weeks) by repeat MRI-PDFF and conventional liver biopsy to examine histological evidence for the resolution of
Other secondary endpoints include changes in clinically relevant biomarkers at 12 and 36 weeks, improvement in fibrosis by at least one stage with no worsening of steatohepatitis, and safety and tolerability. Results at 36-weeks are expected in the second quarter of 2018. Additional information about the study [NCT02912260] can be obtained at www.ClinicalTrials.gov.
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 MGL-3196 is the first orally administered, small-molecule, liver-directed, truly β-selective THR agonist. MGL-3196 has demonstrated the potential for a broad array of therapeutically beneficial effects, improving components of both metabolic syndrome, such as insulin resistance and dyslipidemia, and fatty liver disease, including lipotoxicity and inflammation. These pleiotropic actions, coupled with an excellent safety profile, suggest that MGL-3196 could be the preferred treatment option for
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,” “will,” “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. 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 MGL-3196, the timing and outcomes of clinical studies of MGL-3196, 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
Source: Madrigal Pharmaceuticals, Inc.