Orexigen Announces Positive Clinical Results of Its Proprietary Naltrexone Sustained Release Formulation for Use in ContraveSAN DIEGO--(BUSINESS WIRE)--Sep 25, 2007 - Orexigen(TM) Therapeutics, Inc. (NASDAQ: OREX), a biopharmaceutical company focused on the treatment of central nervous system (CNS) disorders including obesity, today announced positive results in two Phase I clinical trials of its proprietary sustained release (SR) formulation of naltrexone. Orexigen has developed this proprietary SR formulation of naltrexone with the objective of improving tolerability by modifying the pharmacokinetics of immediate release (IR) naltrexone. Naltrexone is a key component of the Company's lead product candidate for obesity, Contrave, which is currently being studied in Phase III clinical trials.
The first trial was conducted among 40 healthy obese subjects and was designed to compare the pharmacokinetics of a single dose of naltrexone IR to a similar dose of naltrexone SR. Results of the trial indicated that the SR formulation reduced naltrexone peak blood concentration, or Cmax, by approximately 25% compared to the older IR formulation while retaining approximately 99% of the exposure to drug, or area-under-the-curve (AUC). The time to peak concentration (Tmax) was also prolonged. In addition, fewer subjects in this trial experienced more than one adverse event with naltrexone SR.
The second trial was designed to evaluate the pharmacokinetics, safety and tolerability profile of naltrexone SR when given in combination with bupropion SR. This was a single-center, randomized, double-blind trial in which 60 healthy obese subjects were randomized to receive bupropion SR and either naltrexone SR or naltrexone IR. The safety analyses suggested that the novel Orexigen naltrexone SR formulation has certain advantages over the naltrexone IR formulation including the following: lower adverse event rates (especially in the gastrointestinal or central nervous systems); lower rate of adverse events categorized as moderate or severe in intensity; and lower rate of two or more adverse events concurrently. The pharmacokinetic analyses indicated a reduction in Cmax and comparable AUC. These pharmacokinetic results were consistent with the results seen in the first trial.
Gary D. Tollefson, M.D.,Ph.D., President and CEO of Orexigen stated, "These results are interesting both from a scientific and a patient perspective. We believe that these results support our hypothesis that lowering naltrexone Cmax and moving absorption of naltrexone out of the stomach contributes to a reduction in the occurrence of the most common adverse events that were seen in our previous Phase II studies including nausea, somnolence, headache and dizziness. From the patient's viewpoint, these data suggest that the new SR formulation may improve overall tolerability, reducing the likelihood that a side effect may lead to early discontinuation of treatment."
Contrave employs a proprietary formulation of two CNS molecules, bupropion and naltrexone, that have been independently approved by the US Food and Drug Administration in other indications. Orexigen chose these two constituent drugs based on the results of a proprietary screening model and the Company's understanding of circuitries in the brain that regulate appetite and energy balance. 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. In a previous Phase IIb multi-center clinical trial, Contrave demonstrated significantly greater weight loss at 48 weeks than the weight loss seen with bupropion SR alone, naltrexone IR alone and placebo.
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), which is in a Phase IIb clinical trial. Both product candidates are designed to 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.
Orexigen cautions you that statements included in this press release that are not a description of historical facts are forward-looking statements. Words such as "believes," "anticipates," "plans," "expects," "indicates," "will," "intends," "potential," "suggests," "assuming" and similar expressions are intended to identify forward-looking statements. These statements are based on Orexigen's current beliefs and expectations. These forward-looking statements include statements regarding the efficacy and safety of the various formulations of Contrave or Empatic, 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. 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 Contrave or 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 described in Orexigen's filings with the Securities and Exchange Commission (SEC), including those detailed under the heading "Risk Factors" in Orexigen's Quarterly Report on Form 10-Q for the quarter ended June 30, 2007 filed with the SEC on August 10, 2007. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and Orexigen undertakes no obligation to revise or update this news release to reflect events or circumstances after the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement. This caution is made under the safe harbor provisions of Section 21E of the Private Securities Litigation Reform Act of 1995.
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Posted: September 2007