- Reported that MGL-3196 demonstrated highly statistically significant results for the primary endpoint in its Phase 2 clinical trial in heterozygous familial hypercholesterolemia (HeFH).
- Announced the acceptance of an abstract for a main plenary presentation at the Annual Meeting of the
European Association for the Study of the Liver(EASL) during The International Liver CongressTM 2018. The abstract summarized 12-week results of Madrigal’s Phase 2 clinical trial of MGL-3196 in patients with non-alcoholic steatohepatitis ( NASH). Those results were presented at EASL by Stephen Harrison, M.D., Principal Investigator of the study as well as Medical Director for Pinnacle Clinical Research, San Antonio, Texas, and Visiting Professor of Hepatology, Oxford University.
“The results to date from our Phase 2 clinical studies of MGL-3196 suggest, in addition to
In addition, in
Clinical Program Summaries for MGL-3196
Non-alcoholic Steatohepatitis (
In October 2016, the first patient was treated in the ongoing Phase 2 trial of MGL-3196 for the treatment of
Patients were randomized to receive either MGL-3196 or placebo in a 2:1 ratio.
The primary endpoint of the study, the reduction of liver fat at 12 weeks compared with baseline (relative change), assessed by magnetic resonance imaging-estimated proton density fat fraction (MRI-PDFF), was achieved. Liver fat was reduced by 36.3% in all MGL-3196 treated patients (78) and 42.0% in a pre-specified group of high exposure MGL-3196 treated patients (44/78), as compared with 9.6% median reduction in liver fat in 38 placebo treated patients. These results were statistically significant (p<0.0001) for both MGL-3196 treatment groups. MGL-3196 was well tolerated with few serious adverse events noted during the 12-week portion of the study, none of which was related to MGL- 3196.
Additional efficacy endpoints are being assessed at the end of the 36-week treatment period based on repeat MRI-PDFF and conventional liver biopsy to examine histologic evidence for the resolution of and improvement in
Results of the 36-week endpoints are expected by the end of
Heterozygous familial hypercholesterolemia (HeFH), and a much rarer form called homozygous familial hypercholesterolemia (HoFH), are severe genetic dyslipidemias typically caused by inactivating mutations in the LDL receptor. Both forms of FH lead to early onset cardiovascular disease. HeFH, the most common dominantly inherited disease, is present in up to 1 in 200 people; the disease is found in higher frequencies in certain more genetically homogenous populations. Treatments exist for both HeFH and HoFH but many patients (as many as 40 percent of HeFH patients) are not able to reach their cholesterol (LDL-C) reduction goals on these therapies, reflecting the lifetime burden of cholesterol buildup in their bodies. Based on evidence of impressive LDL cholesterol lowering in Phase 1, and data suggesting that MGL-3196 has a mechanism of action that is different from and complementary to statins, Madrigal initiated a Phase 2 proof-of-concept trial in HeFH in February 2017 and enrolled 116 patients.
In this Phase 2 HeFH trial, patients who were not at their LDL-C goal were randomized in a 2:1 ratio to receive either MGL-3196 or placebo, in addition to their current cholesterol lowering regimen, which included approximately 75% taking high intensity statins (20/40 mg rosuvastatin or 80 mg atorvastatin), and about 2/3 of patients also taking ezetimibe. MGL-3196 treated patients (placebo corrected) achieved highly significant (p< 0.0001) LDL-C lowering of 18.8%, and 21% LDL-C lowering in those on an optimal dose of MGL-3196. LDL-C lowering was 28.5% in MGL-3196 treated compared to placebo in a prespecified group of patients who did not tolerate high intensity statin doses. Highly significant reductions (p<0.0001) relative to placebo were also observed with ApoB, triglycerides (TG) (25-31%), apolipoprotein CIII (Apo CIII) and Lp(a) (25-40%) in all MGL-3196 treated patients and prespecified subgroups, irrespective of statin treatment.
MGL-3196 was well-tolerated with primarily mild and some moderate AEs, the numbers of which were balanced between placebo and drug-treatment groups.
Financial Results for the Three Months Ended March 31, 2018
Operating expenses were
Research and development expenses for the three month period ended
General and administrative expenses for the three month period ended
Interest income for the three month period ended
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
|Madrigal Pharmaceuticals, Inc.|
|Condensed Consolidated Statements of Operations|
|(in thousands, except share and per share amounts)|
|Three Months Ended|
|Research and development||5,198||4,380|
|General and administrative||1,871||1,695|
|Total operating expenses||7,069||6,075|
|Loss from operations||(7,069||)||(6,075||)|
|Interest income (expense), net||705||76|
|Basic and diluted net loss per common share||$||(0.45||)||$||(0.50||)|
|Basic and diluted weighted average number of common shares outstanding||14,127,868||11,955,739|
|Madrigal Pharmaceuticals, Inc.|
|Condensed Consolidated Balance Sheets|
|March 31,||December 31,|
|Cash, cash equivalents and marketable securities||$||182,825||$||191,527|
|Other current assets||374||485|
|Other non-current assets||279||301|
|Liabilities and Equity|
|Total liabilities and stockholders’ equity||$||183,478||$||192,313|
Source: Madrigal Pharmaceuticals, Inc.