SAN DIEGO -- Orexigen Therapeutics, a biopharmaceutical company focused on the treatment of central nervous system (CNS) disorders including obesity, today announced positive top-line results at the 24 week primary endpoint of its Phase IIb trial of Empatic(TM), one of its two obesity drug candidates. The trial demonstrated, across each of the six Empatic treatment arms, statistically significant weight loss against placebo (p less than .001).
The randomized, double-blind, placebo-controlled trial, conducted with the Company's novel sustained release (SR) formulation of zonisamide paired with bupropion SR, evaluated various ratios of bupropion and zonisamide in 620 patients. At the highest dose tested, patients experienced 8.6% weight loss from baseline compared to 1.1% weight loss for placebo in the intent-to-treat group, and 10.3% weight loss from baseline compared to 1.2% weight loss for placebo in the completer group. In addition, the trajectory of weight loss for all treatment arms appeared to continue downward through 24 weeks.
Results of the trial indicated that Empatic is safe and generally well tolerated. The pooled discontinuation rate for adverse events across the six Empatic dosages was 14%, which was meaningfully lower than the rate in the Company's previous trial employing an older immediate-release form of zonisamide (37%). The pooled discontinuation rate due to adverse events, across the six Empatic dosage groups, was not statistically different than the rate seen with placebo. Adverse events were consistent with the existing package labels for the two constituents and most commonly included headache, nausea, insomnia, anxiety or dry mouth.
"These trial results illustrate that we can delay the early weight loss plateau often seen with dieting and many existing pharmaceutical approaches and also improve tolerability with a sustained release formulation of zonisamide," said Orexigen President and Chief Executive Officer, Gary Tollefson, M.D., Ph.D. "If the magnitude of weight loss evident in this trial continues to be seen, we believe that Empatic may be particularly useful in severely obese individuals."
Empatic employs a proprietary formulation of two CNS molecules, bupropion and zonisamide, that have been independently approved by the US Food and Drug Administration in other indications. Orexigen developed its own proprietary SR version of zonisamide to improve drug tolerability. Bupropion and zonisamide each target reciprocal pathways in the hypothalamus that separately mediate appetite and energy expenditure. The unique combination of these molecules is designed to provide more clinically meaningful weight loss for patients by both initiating weight loss and sustaining it over a longer period of time.
"Despite epidemic rates of obesity, few people seek drug therapy. This may be because, as published reports indicate, currently approved regimens typically achieve only modest weight loss that stalls at an early plateau," said Orexigen Chief Scientific Officer Michael Cowley, Ph.D., scientist and Director of the Electrophysiology Core, Division of Neuroscience at Oregon Health & Science University. "By contrast, our approach is designed to achieve and sustain weight loss by enhancing satiety, diminishing appetite, improving energy expenditure and counteracting the body's efforts to compensate for weight loss."
Additional safety and efficacy data will be reported following completion of an ongoing 24-week trial extension. A detailed presentation of the primary trial results is scheduled to be presented at the 2007 meeting of the North American Association for the Study of Obesity (NAASO), to be held October 20-24 in New Orleans.
About Orexigen Therapeutics
Orexigen Therapeutics, Inc. is a biopharmaceutical company focused on the development of pharmaceutical product candidates for the treatment of central nervous system disorders including obesity. Orexigen's lead combination product candidates targeted for obesity are Contrave(TM), which is in Phase III clinical trials, and Empatic(TM) (formerly Excalia(TM)), which is in a Phase IIb clinical trial. Both product candidates take advantage of the Company's understanding of how the brain appears to regulate appetite and energy expenditure, as well as the mechanisms that come into play to limit weight loss over time. Each product candidate is designed to act on a specific group of neurons in the central nervous system with the goal of achieving appetite suppression and sustained weight loss. Further information about the Company can be found at http://www.Orexigen.com.
Forward-Looking Statements
Orexigen cautions you that statements included in this press release that are not a description of historical facts are forward-looking statements. These forward-looking statements include statements regarding the efficacy and safety of Empatic(TM), and the potential to obtain regulatory approval for, and effectively treat obesity with, any of Orexigen's product candidates. The inclusion of forward-looking statements should not be regarded as a representation by Orexigen that any of its plans will be achieved. The inclusion of forward-looking statements should not be regarded as a representation by Orexigen that any of its plans will be achieved. Actual results may differ from those set forth in this release due to the risk and uncertainties inherent in Orexigen's business, including, without limitation: the progress and timing of Orexigen's clinical trials; the potential that earlier clinical trials may not be predictive of future results; the ability for Empatic to receive regulatory approval on a timely basis or at all; the potential for adverse safety findings relating to Empatic or Contrave to delay or prevent regulatory approval or commercialization, or result in product liability claims; Orexigen and its licensors may not be able to obtain, maintain and successfully enforce adequate patent and other intellectual property protection of its product candidates; and other risks detailed in Orexigen's public filings with the Securities and Exchange Commission. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement and Orexigen undertakes no obligation to revise or update this news release to reflect events or circumstances after the date hereof. This caution is made under the safe harbor provisions of Section 21E of the Private Securities Litigation Reform Act of 1995.