Arena Pharmaceuticals Announces Positive Phase 1b Clinical Trial Results of APD791 for the Treatment of Arterial Thrombosis
SAN DIEGO, July 09, 2008 /PRNewswire-FirstCall/ -- Arena Pharmaceuticals, Inc. today announced positive results from a multiple-ascending dose Phase 1b clinical trial of APD791 to evaluate the compound's safety, pharmacokinetics and pharmacodynamics. APD791 is Arena's internally discovered oral drug candidate intended for the treatment of arterial thrombosis and other related conditions.
The Phase 1b trial was a randomized, double-blind, placebo-controlled, multiple-ascending dose trial in 50 healthy adult male and female volunteers. Daily doses ranged from 15 mg to 240 mg and were generally well tolerated. The most frequently reported adverse event was headache, which was more common in the placebo group than in any APD791 dose group. None of the adverse events occurred in a dose-related fashion with the exception of epistaxis (nose bleed), which occurred in two volunteers in the 240 mg group, a dose outside the anticipated therapeutic range.
In addition to evaluating APD791's safety and tolerability profile, the trial evaluated the pharmacokinetics and pharmacodynamics of multiple oral doses of APD791 over a period of one week. APD791 was rapidly absorbed and exposures were related to dose. Dose-dependent inhibition of serotonin-mediated amplification of platelet aggregation was demonstrated starting at the 15 mg dose and will permit the identification of exposure ranges that produce minimal, moderate and near-complete inhibition of serotonin-mediated platelet aggregation. These results further support APD791's novel mechanism of action and preclinical and Phase 1a clinical trial data.
"These results support APD791's potential to treat a variety of central and peripheral conditions related to arterial thrombosis with a novel mechanism that may provide advantages over currently available therapies," said William R. Shanahan, M.D., Arena's Vice President and Chief Medical Officer. "We will review and evaluate the results with our consultants to develop the best approach to advance APD791 into Phase 2 clinical trials. We are also actively exploring partnership opportunities for this candidate."
"These positive results also demonstrate the utility of our focus on G protein-coupled receptor (GPCR) drug research and the general approach we take toward developing innovative treatments for serious medical conditions. Applying our GPCR focus and expertise, we've developed a pipeline of seven novel development stage drug candidates, five of which are in the clinic," stated Dominic P. Behan, Ph.D., Arena's Senior Vice President and Chief Scientific Officer.
APD791 is a novel, oral and selective inverse agonist of the 5-HT2A serotonin receptor. Serotonin activation of the 5-HT2A receptor on platelets and vascular smooth muscle is thought to play an important role in events leading to thrombosis, and elevated serotonin levels have been associated with increased cardiovascular risk. Normally, when a platelet is activated by one of a number of factors, such as thrombin or collagen, the platelet releases serotonin, which, based on preclinical studies, promotes platelet aggregation, vasoconstriction and intimal hyperplasia. By blocking activation of the 5-HT2A receptor on platelets and other cardiovascular tissues, APD791 may curb these serotonin-mediated effects in the clinical setting, thereby reducing or preventing thrombosis. Furthermore, based upon preclinical studies, Arena believes that APD791, by preventing only the amplification of platelet aggregation induced by primary aggregators such as ADP and collagen, may allow sufficient platelet aggregation at therapeutic doses to avoid the bleeding risk associated with other anti-platelet agents while preventing the robust activation of platelets needed to cause thrombosis. In a Phase 1a clinical trial, dose-dependent inhibition of serotonin-mediated amplification of platelet aggregation was demonstrated, supporting the preclinical data generated around APD791 and establishing initial clinical validation for APD791's novel mechanism of action.
Thrombosis is the formation of a clot, or thrombus, inside a blood vessel that restricts the flow of blood. The formation of a thrombus is often caused by an injury to the wall of a blood vessel. The injury to the blood vessel activates platelets, which then aggregate and adhere to one another as they start to release certain factors, including serotonin, that facilitate thrombosis. Thrombi that form in diseased atherosclerotic arteries of the heart may cause acute coronary syndrome or myocardial infarction, and thrombi that form in the vessels of the brain may cause stroke.
The American Heart Association estimates that in the United States over 13.9 million people alive in 2005 had survived either a myocardial infarction or a stroke. To reduce the risk of future events, many patients receive daily anti-thrombotic therapy.
About Arena Pharmaceuticals
Arena is a clinical-stage biopharmaceutical company focused on discovering, developing and commercializing oral drugs in four major therapeutic areas: cardiovascular, central nervous system, inflammatory and metabolic diseases. Arena's most advanced drug candidate, lorcaserin, is being investigated in a Phase 3 clinical trial program for the treatment of obesity. Arena's broad pipeline of novel compounds target G protein-coupled receptors, an important class of validated drug targets, and includes compounds being evaluated independently and with partners, including Merck & Co., Inc. and Ortho-McNeil Pharmaceutical, Inc.
Arena Pharmaceuticals(R) and Arena(R) are registered service marks of the company. "APD" is an abbreviation for Arena Pharmaceuticals Development.
Certain statements in this press release are forward-looking statements that involve a number of risks and uncertainties. Such forward-looking statements include statements about the therapeutic range of APD791 and the exposures which may produce minimal, moderate or near-complete inhibition of serotonin-mediated amplification of platelet aggregation; the potential for APD791 to provide advantages over currently available therapies; determination of the best approach to advance APD791 into Phase 2 clinical trials; the tolerability, side effects and efficacy of APD791; the role of serotonin in thrombosis and in increasing cardiovascular risk; how APD791 is believed to work and its intended use and therapeutic potential; and about Arena's strategy, internal and partnered programs, and ability to develop compounds and commercialize drugs. For such statements, Arena claims the protection of the Private Securities Litigation Reform Act of 1995. Actual events or results may differ materially from Arena's expectations. Factors that could cause actual results to differ materially from the forward-looking statements include, but are not limited to, Arena's planned clinical trials and studies may not proceed at the time or in the manner Arena expects or at all, the results of preclinical studies or clinical trials may not be predictive of future results, Arena's ability to partner lorcaserin, APD125, APD791 or other of its compounds or programs, the timing, success and cost of Arena's research, out-licensing endeavors and clinical trials, Arena's ability to obtain additional financing, Arena's ability to obtain and defend its patents, and the timing and receipt of payments and fees, if any, from Arena's collaborators. Additional factors that could cause actual results to differ materially from those stated or implied by Arena's forward-looking statements are disclosed in Arena's filings with the Securities and Exchange Commission. These forward-looking statements represent Arena's judgment as of the time of this release. Arena disclaims any intent or obligation to update these forward-looking statements, other than as may be required under applicable law.
Contacts: Jack Lief Mary Claire Duch President and CEO WeissComm Partners Media Relations 212.301.7228 David Walsey Director, Corporate Communications Arena Pharmaceuticals, Inc. 858.453.7200, ext. 1682
CONTACT: Jack Lief, President and CEO, or David Walsey, Director,Corporate Communications, +1-858-453-7200, ext. 1682, both of ArenaPharmaceuticals, Inc.; or Media Relations, Mary Claire Duch of WeissCommPartners, +1-212-301-7228, for Arena Pharmaceuticals, Inc.
Web site: http://www.arenapharm.com/
Ticker Symbol: (NASDAQ-NMS:ARNA)
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Posted: July 2008