West Coast Editor

Shares of Arena Pharmaceuticals Inc. enjoyed the benefit of positive data from a Phase IIb trial with the firm's 5-HT2C serotonin receptor agonist for obesity, which trimmed overweight patients an average of 4, 5.7 and 7.9 pounds at daily doses of 10, 15 and 20 mg respectively.

Patients on placebo lost an average of just 0.7 pounds. Wall Street took notice of the difference, and rewarded Arena's stock (NASDAQ:ARNA), which closed Wednesday at $13.48, up $2.07, or 18 percent.

"We hope to be in Phase III around the middle of next year," said Jack Lief, San Diego-based Arena's president and CEO.

The drug, APD356, was generally well tolerated at all doses, with no apparent effects on heart valves or pulmonary artery pressures, suggesting a side effect profile superior to that of would-be competitor, Meridia (sibutramine hydrochloride monohydrate), from Knoll Pharmaceutical Co., of Mt. Olive, N.J.

Meridia "has an [FDA] warning about hypertension and there have been some deaths," Lief said, adding dryly, "Other than that, it's a great drug."

Arena's trial enrolled 469 male and female obese patients with a body mass index of between 29 and 46. Patients were randomized into four groups to evaluate three doses, the 20-mg dose being split into 10 mg before breakfast and 10 mg before dinner.

That 20-mg dose was designed to provide similar peak blood levels as the 15-mg once daily dose, but higher blood trough levels, thereby maintaining higher average drug concentrations in the blood, as well as to bring about a second peak in drug level to cover the evening hours.

Along with the usual safety evaluations, patients were assessed by echocardiogram before they signed up and at the end of the treatment period. None were given diet or exercise advice but were required to abstain from alcohol during the study.

Arena, focused on G protein-coupled receptors as targets, plans an end-of-Phase II meeting with the FDA, with a Phase III trial slated for next year. Aside from Meridia, another drug is on the market - Xenical (orlistat), from Nutley, N.J.-based Hoffmann-La Roche Inc., which works by blocking the absorption of fat in the gastrointestinal tract.

"People hate it because of side effect issues," Lief said. Those are mainly changes in bowel habits, which some users have characterized as being "like excreting grease." Arena's drug aims to provide efficacy without risks or unpleasantness.

Other up-and-comers exist. Sanofi-Aventis Group, of Paris, won acceptance from the FDA of its filing of a new drug application for rimonabant, trademarked Acomplia, a cannabinoid Type 1 blocker for obesity.

Lief said he expects Acomplia to win approval before Arena's compound and to become a billion-dollar drug.

"The market needs a viable drug in obesity, and we're really happy that they're going to pave the way before us," he said, calling the patient base "substantial enough so that even if there are five or six or 15 drugs, they could each be billion-dollar drugs."

Roche and another big pharma, London-based GlaxoSmithKline plc, have separate 5-HT2C programs, as well. The former is collaborating with UK-based Vernalis plc, and the latter's program came from an agreement with Stockholm, Sweden-based Biovitrum AB in a $150 million deal made three years ago.

Vernalis said in February that a development candidate had been selected by Roche and was undergoing preclinical studies, which, if successful, would lead to further development by the pharma firm. Less is known of GSK's efforts.