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Arena Pharmaceuticals Initiates Phase 2 Efficacy Study for Its Novel Anti-Obesity Compound
PR Newswire via NewsEdge Corporation : SAN DIEGO, Dec. 22 /PRNewswire-FirstCall/ -- Arena Pharmaceuticals, Inc. (Nasdaq: ARNA) announced today that it has started dosing patients in a Phase 2 clinical trial of APD356, an orally administered small molecule designed to regulate satiety for the treatment of obesity. This compound is a selective agonist of 5-HT2C serotonin receptors, which are concentrated in the hypothalamus, an area of the brain known to play an important role in regulating food intake and metabolism.
This Phase 2 clinical trial of APD356 is a randomized, double-blinded, multiple-dose, 28-day trial examining 400 obese volunteers. Arena expects that the trial will compare doses of 1, 5 and 15 mg of APD356 to a placebo and will evaluate weight loss after administration once daily for 28 days. Doses for the Phase 2 trial were chosen to bracket the 10 mg dose that evidenced a pharmacologic signal (a reduction in meal size) with a single dose in Arena's Phase 1a trial. The 1 mg dose was chosen as the lowest dose because Arena believes that a 1 mg dose has the potential to produce therapeutic drug levels in the central nervous system if APD356, as observed in rats, achieves higher concentrations in the human brain than in blood. Arena expects to announce initial results from this trial in the second quarter of 2005.

The initiation of this Phase 2 trial of our lead anti-obesity compound marks a significant achievement for Arena, stated Jack Lief, Arena's President and CEO. This strengthens our pipeline of compounds, which have the potential to treat major unmet medical needs. We anticipate that this Phase 2 study will provide further favorable safety data and validate the preliminary efficacy data observed in earlier pre-clinical studies of APD356.

About APD356.

Obesity and metabolic syndrome are conditions that affect tens of millions of adults and children and pose a serious long-term threat to their health and welfare. In two previous Phase 1 clinical trials, APD356 was well tolerated at doses up to 20 mg once daily for 14 days and the compound evidenced a pharmacological effect on food intake with a single 10 mg dose. Side effects were similar to placebo at the 3 and 10 mg doses of APD356, but tended to occur more frequently than placebo at the 20 mg dose. The most common side effects, occurring primarily at the 20 mg dose, were headache, nausea and vomiting. These side effects were occasional and generally mild in nature. In addition, APD356 demonstrated predictable pharmacokinetic behavior and a half-life potentially sufficient to allow once daily dosing.

In animal models of obesity, APD356 reduced body weight and food intake, which Arena believes is due to the compound's ability to regulate satiety and perhaps metabolism. Arena's in vivo experiments showed a desirable outcome by demonstrating that APD356 selectively reduced fat mass in obese animals, while leaving lean body mass unchanged. Stimulation of the 5-HT2C receptor is thought to play an important role in food intake. APD356 has approximately 100-fold selectivity in vitro for the 5-HT2C receptor relative to the 5-HT2B receptor, which Arena believes is the receptor primarily implicated in the cardiac valvulopathy observed with non-selective serotonergic drugs. In addition, APD356 has approximately 15-fold selectivity in vitro for the 5-HT2C receptor versus the 5-HT2A receptor, the central nervous system (CNS) receptor thought to be primarily responsible for most of the CNS adverse effects of non-selective serotonergic agents. Arena believes that the selectivity of APD356 may allow the compound to be dosed at a well-tolerated level that will induce clinically relevant weight loss without the side effects observed with non-selective serotonergic agents.

About Arena Pharmaceuticals.

Arena is a biopharmaceutical company focusing on the discovery, development and commercialization of drugs in four major therapeutic areas: metabolic, cardiovascular, inflammatory and central nervous system diseases. Arena is developing a broad pipeline of highly selective compounds that act on an important class of drug targets called G protein-coupled receptors, or GPCRs, and that are being developed using Arena's proprietary technologies, including CART(TM) (Constitutively Activated Receptor Technology) and Melanophore. Arena's most advanced clinical compound is APD356, an anti- obesity compound that is a selective 5-HT2C serotonin receptor agonist. Arena is also pursuing Phase 1 clinical trial evaluation of APD125, a compound with a novel mechanism (selective 5-HT2A receptor antagonism) for the treatment of insomnia. Arena recently announced the initiation of a global diabetes collaboration with Ortho-McNeil Pharmaceutical, a Johnson & Johnson company, and the extension and expansion of its collaboration with Merck & Co. for cardiovascular disease.

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 relating to Arena's Phase 2 clinical trials of APD356 and activities expected to occur in connection with such clinical trial, the potential for a 1 mg dose of APD356 to produce therapeutic drug levels in the central nervous system (or CNS), anticipated results from the Phase 2 clinical trial of APD356, the effects of administration of APD356, including APD356's safety profile, potency, pharmacological behaviour and half-life, expectations for future safety and efficacy data and results relating to APD356, about when and whether Arena expects to continue further clinical testing on APD356 and APD125 and about Arena's strategy, technologies, pre-clinical and clinical programs, and ability to identify and develop drugs, as well as other statements that are not historical facts. 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, the risk that the results of preclinical and initial clinical trials may not be predictive of future results, and that APD356 may not have favorable results in the Phase 2 clinical trial discussed in this press release or later clinical trials, if any, the timing, success and cost of Arena's research, out-licensing endeavors and clinical studies, Arena's ability to obtain additional financing, and the timing and receipt of payments and fees, if any, from Arena's collaborators, including Ortho-McNeil and Merck. 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 SEC reports, including Arena's most recent quarterly report on Form 10-Q. These forward-looking statements represent Arena's judgment as of the date of this release. Arena disclaims any intent or obligation to update these forward- looking statements.