Madrigal Pharmaceuticals Launches Multiple Dose Phase I Clinical Study for 3196 in Dyslipidemia
Published: Mar 05, 2012
FORT WASHINGTON, PA--(Marketwire - March 05, 2012) - Madrigal Pharmaceuticals, a development company focused on novel small-molecule drugs addressing major unmet needs in cardiovascular and metabolic diseases, today announced that the first human volunteers have been dosed in a multiple dose Phase I clinical trial of the Company's lead product candidate, 3196.
3196 is a liver-directed thyroid hormone receptor-beta (THR-ß) agonist for the treatment of hypercholesterolemia, or high blood cholesterol levels, and other dyslipidemias. It is designed to specifically target receptors in the liver involved in metabolism and cholesterol regulation, delivering the validated benefits of THR-ß agonism, which include a lowering of LDL cholesterol, triglycerides and Lp(a), while avoiding the side effects associated with receptor activation outside the liver. Preclinical studies in a variety of animal models demonstrated 3196's safety advantages relative to other thyroid hormone ß-agonists profiled. A single ascending dose Phase I study of 3196 was recently completed, and the drug was found to be safe and well-tolerated at all doses tested.
"Dyslipidemias are a leading factor in the formation of atherosclerosis, a hardening of the arteries which can lead to major adverse cardiovascular events such as heart attack and stroke," said Rebecca Taub, M.D., Chief Executive Officer of Madrigal Pharmaceuticals. "By targeting THR-ß in the liver, 3196 may reduce dyslipidemia while avoiding potential side effects associated with systemic activation of the thyroid hormone receptors. Initial safety has been demonstrated in both our single dose and now multiple dose studies. We look forward to characterizing the efficacy of this potentially important compound, and to understanding its benefit in a variety of significant unmet needs."
The Phase I clinical trial is a multiple dose study to evaluate the safety, pharmacokinetics and pharmacodynamics of 3196 in healthy subjects with mildly elevated LDL cholesterol. The single-center trial, which will enroll approximately 40 subjects, is being conducted by Cetero Research at its clinical study site in Fargo, ND. Results from the study are expected mid-year 2012.
Following a successful outcome, Madrigal intends to investigate the possibility of using 3196 alone or in combination with statins for the treatment of hypercholesterolemia in high risk cardiovascular patients whose LDL cholesterol is not controlled by statins alone, and in patients with genetic dyslipidemias such as familial hypercholesterolemia and mixed dyslipidemia.
3196 is an orally administered, small-molecule ß-selective THR agonist designed to specifically target receptors in the liver involved in metabolism and cholesterol regulation, and avoid side effects associated with thyroid hormone receptor activation outside the liver, including those mediated by THR-a receptors. The mechanisms by which 3196 lowers cholesterol are distinct from and complementary to statins. Preclinical studies demonstrated a rapid reduction of non-HDL cholesterol and the drug was shown to be synergistic with statins in animal studies. THR-ß agonists are believed to promote reverse cholesterol metabolism by causing increased uptake of cholesterol into the liver and increased cholesterol elimination from the body through excretion into the bile. The compound also reduces triglycerides in the plasma and liver by increasing fat metabolism.
About Madrigal Pharmaceuticals, Inc.
Madrigal Pharmaceuticals, Inc. is a company focused on the development of novel compounds for the treatment of cardiovascular and metabolic diseases. Madrigal's drug candidates include 3196 and other compounds that address the underlying causes of metabolic and cardiovascular disease: high cholesterol and diabetes. For more information, visit: http://www.madrigalpharma.com.
Madrigal Pharmaceuticals, Inc.
Rebecca Taub, M.D.
Chief Executive Officer