SAN DIEGO, Jan. 9 /PRNewswire-FirstCall/ -- Arena Pharmaceuticals, Inc. today announced positive results from a single dose Phase 1a clinical trial of APD791 and the initiation of a multiple dose Phase 1b clinical trial to further evaluate the compound’s safety, pharmacokinetics and pharmacodynamics. APD791 is Arena’s internally discovered oral drug candidate intended for the treatment of arterial thrombosis.
The Phase 1a trial was a randomized, placebo-controlled, double-blind, single-ascending dose trial in 90 healthy male and female volunteers. Doses originally intended for study ranged from 1 mg to 160 mg, but due to excellent tolerability the maximum dose was increased to 320 mg. Doses were well tolerated, without any dose related adverse events, such that a maximum tolerated dose could not be defined despite achieving high concentrations in blood. APD791 was rapidly absorbed and exposures were generally related to dose. Terminal half-life (t1/2) of the parent plus active metabolites was also related to dose, and was approximately 11 hours at the higher doses. Dose dependent inhibition of serotonin-mediated amplification of platelet aggregation was demonstrated starting at the 1 mg dose, supporting APD791 preclinical data and establishing initial clinical validation of APD791’s novel mechanism of action.
Based on the positive Phase 1a results, a Phase 1b trial was initiated. The Phase 1b trial is a randomized, placebo-controlled, double-blind, multiple-ascending dose trial in up to 50 healthy male and female volunteers between the ages of 19 and 45 years old. In addition to evaluating APD791’s safety and tolerability profile, the trial will also evaluate the pharmacokinetics and pharmacodynamics of multiple oral doses of APD791 over a period of one week. Results from the Phase 1b trial are anticipated in mid 2008.
“We are encouraged by these early results and look forward to the results from the Phase 1b trial around the middle of the year,” said William R. Shanahan, M.D., Arena’s Vice President and Chief Medical Officer.
About APD791
APD791 is a novel, orally available and selective inverse agonist, or inhibitor, 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 (or thickening of the vessel wall). 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 the risk of 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. APD791 demonstrated improved coronary artery flow in a preclinical study using the Folts model, an established model of acute coronary syndrome.
About Thrombosis
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 13.6 million people alive in 2004 had survived either a myocardial infarction or a stroke. To reduce the risk of future events, many patients receive daily anti-thrombotic therapy.
Forward-Looking Statements
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 protocol, design, scope and other aspects of the Phase 1b clinical trial of APD791; the timing of the results from the Phase 1b clinical trial of APD791; 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 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.
CONTACT: Jack Lief, President and CEO, or David Walsey, Director,
Corporate Communications, both of Arena Pharmaceuticals, Inc.,
+1-858-453-7200, ext. 1682; or Mary Claire Duch of WeissComm Partners,
Media Relations, +1-212-301-7228, for Arena Pharmaceuticals, Inc.
Web site: http://www.arenapharm.com/
