>>Metabasis Therapeutics Announces Initiation of a Clinical Trial for MB07811, Its Novel Product Candidate for the Treatment of Hyperlipidemia
Wednesday June 20, 9:00 am ET
SAN DIEGO--(BUSINESS WIRE)--Metabasis Therapeutics, Inc. (Nasdaq:MBRX - News), a biopharmaceutical company focused on the discovery, development and commercialization of novel drugs for the treatment of metabolic and liver diseases by targeting the liver and liver pathways, announced today that it has initiated a Phase 1b clinical trial for MB07811, a novel, orally active product candidate for the management of hyperlipidemia. MB07811, Metabasis' fifth internally discovered product candidate in clinical development, uses the Company's proprietary HepDirect® prodrug technology to target a novel beta-subtype-selective thyroid hormone receptor (TR beta) agonist to the liver to reduce serum cholesterol (LDL) and triglycerides (TGs).
The Company successfully completed a Phase 1a clinical trial for MB07811 at the end of 2006, which provided evidence that the candidate is safe and well-tolerated when administered as a single dose. The current clinical trial, designated as a Phase 1b study, will be a 14-day, multiple dose trial in healthy volunteers with modestly elevated LDL-cholesterol levels. The clinical trial will evaluate the safety and tolerability of MB07811 in approximately 60 patients, and could potentially provide preliminary evidence of cholesterol-lowering activity and evidence of an improvement of the therapeutic index, a key property that the liver-targeting is designed to address. The therapeutic index is a measure of the relative safety of a drug for a particular treatment and is defined as the ratio between the toxic dose and the therapeutic dose of a drug.
Thyroid hormone receptor (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 liver-targeting could improve the therapeutic index by avoiding the extra-hepatic activation of thyroid receptors that may lead to therapy-limiting side effects.
High levels of cholesterol and triglycerides are associated with an increased risk of cardiac disease, and fatty liver is associated with increased risk of diabetes and chronic liver disease. Preclinical studies demonstrated that MB07811 significantly lowers LDL- and total cholesterol and triglyceride 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®) and provided an additive benefit when administered in combination with this widely used statin. Some of these findings were presented by Metabasis last week at the Endocrine Society's 89th Annual Meeting.
"We believe that liver-targeting may avoid therapy-limiting side effects previously seen with non-liver-targeted TR beta agonists and thus unlocks the therapeutic potential of this approach," commented Dr. Mark Erion, executive vice president, research and development and chief scientific officer. "We feel that MB07811 could prove to be the first in an important new class of therapies for hyperlipidemia which, even with the availability of statins, remains inadequately treated in many patients."
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.
"This year is turning out to be a very exciting one for Metabasis," stated Dr. Paul Laikind, president and chief executive officer. "With five important product candidates at various stages of clinical development, we are making significant progress. So far, in addition to this new trial for MB07811, we initiated a Phase 2a clinical trial for our second generation diabetes product candidate, MB07803, and we could have data from both these studies toward the end of the year. In the meantime, we are eagerly awaiting the data from a Phase 2b clinical trial, conducted by our partner Daiichi-Sankyo on our first generation diabetes product candidate, CS-917, expected later this summer. Meanwhile, work on our two liver disease products, MB07133 and pradefovir, continues.<<
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OK, another little deadline met, good. I imagine analysts on the 2nd quarter CC will be asking when the data from this P1b will be announced; I'd like to know, too. It should move the stock a bit more than the prior trial, because, as the PR says, this trial "could potentially provide preliminary evidence of cholesterol-lowering activity and evidence of an improvement of the therapeutic index, a key property that the liver-targeting is designed to address." So this is somewhat proof of concept. Being a 14 day trial, I'd expect data by year end, unless enrollment sucks . . . but I have no feel for how quickly such a trial should enroll, which is why I'll be interested in hearing about that on the upcoming CC.
And management is not the only one "eagerly awaiting the data from a Phase 2b clinical trial, conducted by our partner Daiichi-Sankyo on our first generation diabetes product candidate, CS-917, expected later this summer." Fall begins in three long months . . . sigh.
Cheers, Tuck |
