Metabasis Announces Preliminary Safety and Efficacy Results from an Ongoing Phase 1b Clinical Trial for MB07811, Its Novel Product Candidate for the Treatment of Hyperlipidemia
Jan 4, 2008 09:00:04 (ET)
SAN DIEGO, Jan 04, 2008 (BUSINESS WIRE) -- Metabasis Therapeutics, Inc. (MBRX, Trade ) announced today that it has completed the four protocol-defined dose groups in its Phase 1b multiple-dose clinical trial evaluating the safety and tolerability of MB07811, its novel product candidate for the treatment of hyperlipidemia. Preliminary results from this ongoing trial indicate that MB07811 is safe and well tolerated at the doses studied, and based on these findings, the Company plans to explore the safety and tolerability of higher doses. In addition, the Company announced that the preliminary results from this trial suggest that MB07811 reduced fasting low-density lipoprotein (LDL) cholesterol levels, as well as fasting triglyceride (TG) levels.
MB07811 is a novel, orally administered, beta-subtype-selective thyroid hormone receptor (TR beta) agonist that is designed to specifically target the liver and thereby avoid well known side effects of thyroid hormone receptor (TR) agonists at doses that reduce LDL-cholesterol and TG levels. The Phase 1b clinical trial is evaluating MB07811 dosed once-a-day for 14 days in healthy volunteers (eight subjects per cohort: six administered MB07811 and two administered a placebo) with serum LDL-cholesterol levels greater than 100 mg/dL.
The trial was designed to study safety and tolerability of four doses of MB07811 (0.25 mg, 1 mg, 2.5 mg and 5 mg). Because these doses were found to be safe and well tolerated, Metabasis plans to evaluate a dose of 10 mg and to escalate to higher doses if the 10 mg dose proves to be safe and well tolerated. The preliminary results of the trial also suggest that MB07811 reduced LDL-cholesterol and TG levels following administration of MB07811 for 14 days.
TR agonists represent a novel and potentially important approach for reducing LDL-cholesterol (known as the "bad" cholesterol) and total cholesterol, liver and serum triglycerides and lipoprotein (a) (Lp(a)). However, use of this approach has been hampered by well-known side effects associated with thyroid hormone, which include cardiac effects, as well as, effects on the thyroid hormone axis, muscle metabolism and bone turnover. Metabasis believes that the combination of a TR beta-selective receptor agonist and its proprietary liver-targeting could improve the therapeutic index by avoiding the extra-hepatic activation of thyroid receptors that may lead to therapy-limiting side effects.
"We are very pleased with the results seen to date with MB07811," commented Dr. Paul Laikind, president and chief executive officer. "The safety and tolerability observed at the doses evaluated in this on-going study combined with the preliminary evidence of efficacy is very encouraging. We believe that liver-targeting may avoid the therapy-limiting side effects previously seen with non-liver-targeted TR beta agonists and thus unlock the therapeutic potential of this approach. MB07811 could prove to be the first in an important new class of therapies for hyperlipidemia with a unique profile that combines total and LDL-cholesterol reduction with significant reductions in serum and liver TGs and Lp(a). Our plans for MB07811 in 2008 include completion of the current trial, as well as a Phase 2 proof-of-concept clinical trial in patients with elevated cholesterol levels and a drug-drug interaction trial with a statin."
High levels of cholesterol and triglycerides are associated with an increased risk of cardiac disease and fatty liver, which results from high levels of liver TGs and is associated with an increased risk of diabetes and chronic liver disease. Preclinical studies demonstrated that MB07811 significantly lowers LDL and total cholesterol and TG levels and in certain animal models, reduces liver fat content, all with a significantly improved safety profile relative to non-liver-targeted TR beta agonists. Oral administration of MB07811 in a primate model led to cholesterol-lowering comparable to atorvastatin (Lipitor(R)) and provided an additive benefit when administered in combination with this widely used statin.
Cardiovascular disease is the leading cause of death worldwide and in the U.S. alone, claims more lives than cancer, chronic respiratory diseases, accidents and diabetes combined. Patients with hyperlipidemia, a clinical condition characterized by an elevation of cholesterol and/or triglycerides in the bloodstream, are at greater risk of cardiovascular disease and of experiencing a heart attack or stroke. Even though many patients take medications designed to lower serum cholesterol, such as statins, more than half of patients with hyperlipidemia are reported to remain above the targeted levels set by the National Cholesterol Education Program. Although effective for treating many patients with elevated LDL-cholesterol, statins have little affect on TGs.
About Metabasis ( www.mbasis.com ):
Metabasis Therapeutics is a biopharmaceutical company focused on the discovery, development and commercialization of novel drugs by applying our proprietary technology, scientific expertise and unique capabilities for targeting the liver and liver pathways. We have established a broad pipeline of product candidates and advanced research programs targeting large markets with significant unmet medical needs. Our primary focus is on drug candidates to treat metabolic diseases such as diabetes, hyperlipidemia and obesity, among others. We have also advanced drug candidates to treat liver diseases such as hepatitis and primary liver cancer, however, we are currently not seeking new drug candidates in that area of focus. We have discovered all of our product candidates internally using our proprietary technologies.
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