Orexigen Therapeutics Inc. reported positive top-line data from a Phase IIb study of Empatic, the company's second program aimed at the sizeable - and still growing - obesity market.
While the full data set will be presented at the North American Association for the Study of Obesity meeting in New Orleans this fall, the company reported that Empatic, a drug that combines the sustained formulations of approved epilepsy drug zonisamide plus the antidepressant buproprion, demonstrated statistically significant weight loss vs. placebo. At the highest dose tested, patients experienced an 8.6 percent weight reduction from baseline compared to 1.1 percent for placebo in the intent-to-treat group. In the completer group, a 10.3 percent weight loss from baseline was observed for patients receiving Empatic compared to 1.2 percent for placebo.
Data showed "the magnitude of the weight reduction coupled with a very nice" safety profile, said Gary Tollefson, president and CEO of San Diego-based Orexigen. Perhaps, most notably, the results suggested that Empatic can maintain the weight loss over a long period of time.
There already are anti-obesity drugs on the market, and while they might be effective in initiating weight loss, patients "hit a plateau, often between 16 and 24 weeks of treatment, sometimes earlier," Tollefson said.
Orexigen's CNS approach aims at managing obesity via the central nervous system, specifically the hypothalamus, which regulates eating and metabolic activity. That approach also targets the "brain's compensatory mechanisms," which work against drugs to preserve weight loss.
The ability to sustain weight reduction also has been demonstrated by the company's lead obesity program, Contrave, which entered Phase III testing a few months ago. That product, a formulation of buproprion and naltrexone, demonstrated in a Phase IIb study statistically significant weight loss after 48 weeks of treatment compared to sustained-release buproprion alone, immediate-release naltrexone alone and placebo. Pending positive Phase III data, Orexigen anticipates filing for regulatory approval of Contrave in the second half of 2009.
Empatic is about 12 to 18 months behind Contrave in development, Tollefson told BioWorld Today. The company expects to conduct another Phase IIb study comparing Empatic to buproprion alone and zonisamide alone before moving the product into pivotal trials.
If both drugs ultimately gain approval, Tollefson said they would not compete against each other; rather, both would allow Orexigen to reach a larger range of obese patients.
"Both drugs work by two different mechanisms," he said, "and we are positioning them for two different markets. There isn't just one phenotype of obesity."
Contrave is designed for initiating and maintaining weight loss, along with managing behavioral aspects of obesity, such as food cravings, and also addressing depression, a frequent comorbid condition of obesity, Tollefson said. Empatic, on the other hand, likely would be for patients with a higher body mass index, those who are severely obese to the point of considering surgical options.
Orexigen holds all rights to both drugs, though the company has said it might seek a commercialization partner.
According to the Centers for Disease Control and Prevention, about a third of Americans are obese and another third are classified as overweight, and both categories are growing, making obesity an appealing market for many companies, such as San Diego-based Arena Pharmaceuticals Inc., which recently completed enrollment in the first of three Phase III studies of lorcaserin hydrochloride, which targets the 5-HT2c serotonin receptor in the hypothalamus to regulate satiety and metabolic rate.
Another firm, Vivus Inc., of Mountain View, Calif., is getting ready to move into Phase III with its product Qnexa, which is formulated with low doses of the FDA-approved diet drug phentermine combined with topiramate, a drug approved for epilepsy and for migraine prevention.
San Diego-based Amylin Inc. also is in late-stage development with pramlintide, a neurohormone, and big pharma firms Pfizer Inc., of New York, and Merck & Co. Inc., of Whitehouse Station, N.J., are in Phase III development with cannabinoid-1 blockers CP-945588 and MK-0364, respectively.
Rimonabant, another CB-1 blocker, had been under FDA review until last month, when its developer, Paris-based Sanofi-Aventis, pulled the application following a negative opinion from an FDA advisory committee. The product previously was approved in Europe, where it is sold under the brand Acomplia.
Already approved in the U.S. are obesity drugs Xenical, a lipase inhibitor from Basel, Switzerland-based F. Hoffmann-La Roche Ltd., along with Meridia, a monoamine re-uptake inhibitor from Abbott Park, Ill.-based Abbot and Alli, an over-the-counter version of Xenical sold by London-based GlaxoSmithKline plc.
As an offshoot to its obesity program, Orexigen plans to investigate formulations of different components with the aim of mitigating the weight gain side effects of atypical antipsychotic medications. Tollefson said that program is in preclinical development. The company also is conducting early stage work in other indications, such as schizophrenia and obsessive compulsive disorder.
Shares of Orexigen (NASDAQ:OREX), which traded as high as $15.25 Tuesday, ended the day at $14.24, up 2 cents.