OREXIGEN Therapeutics Reports 48-Week Results of Phase IIb Trial of Empatic to Treat Obesity
This randomized, double-blind, placebo-controlled trial was the Company's first large, multi-center trial of its novel sustained release, or SR, formulation of zonisamide paired with bupropion SR. The primary trial objective was to determine the optimal dose ratios of bupropion and zonisamide. The trial randomized 623 obese patients and included only a minimal diet and exercise intervention.
The trial protocol permitted all patients who completed 24 weeks of treatment to continue on their existing double-blind therapy for an additional 24 weeks. Alternatively, patients who failed to achieve at least a 5% response 24 weeks after the start of treatment were permitted to switch to the highest Empatic dose in a 24-week open label extension. Most patients receiving Empatic therapy elected to continue on their existing double-blind therapy for an additional 24 weeks and continued to lose weight in the time period from weeks 24 to 48. Analysis of their weight loss, as specified by the study protocol, is referred to as the ITT--double blind extension. Patients from this group who completed treatment through week 48 are referred to as completers--double blind extension. Except with respect to the placebo patients, as explained below, only data for patients remaining on double-blind treatment beyond week 24 were included in the analysis and data from patients discontinuing blinded therapy through week 24 were not imputed. The double-blind extension results are detailed as follows: -0-
Weight loss @ 48 weeks ------------------------ Zonisamide SR Bupropion SR ITT - Completers - Double Double Blind Blind Extension Extension ----------------------------------------------------------- Group 1 120mg 280mg 10.1% 12.1% Group 2 120mg 360mg 12.1% 11.8% Group 3 240mg 280mg 11.8% 12.4% Group 4 240mg 360mg 12.0% 12.5% Group 5 360mg 280mg 10.8% 11.0% Group 6 360mg 360mg 14.0% 15.1% Group 7 * Placebo Placebo 1.1% 1.2% ---------- * Represents placebo weight loss at 24 weeks. The study design for the trial permitted patients who did not achieve a 5% weight loss from baseline to switch to the highest Empatic dose after 24 weeks. Because most (approximately 88%) of the placebo patients did not achieve a 5% clinical response at 24 weeks, most (approximately 79%) of the placebo patients who completed 24 weeks switched into the highest Empatic dose. This aspect of the trial, which permitted patients not achieving a 5% response to switch to the highest Empatic dose after 24 weeks, introduces selection bias for patients most likely to lose weight and enhances the results for all groups in the trial. However, the impact is greatest in the placebo arm because of the significantly higher proportion of placebo patients who switched to the highest Empatic dose after 24 weeks. As such, data for the actual 48-week double-blind placebo treatment arm are not presented.
Results of this trial also indicated that Empatic, which included Orexigen's proprietary zonisamide SR formulation, was safe and generally well tolerated. As reported previously, the overall rate of discontinuation due to adverse events for the Empatic treatment arms through the primary endpoint at 24 weeks was not statistically different than the rate seen with placebo. This was also true with the highest Empatic dose as compared to placebo. Between 24 and 48 weeks, the overall rate of discontinuation due to adverse events among the double-blind extension group receiving Empatic was less than 2%. Moreover, the discontinuation rate due to adverse events in the double-blind group of patients receiving the highest Empatic dose between weeks 24 and 48 was 0%. Adverse events were consistent with the existing package labels for one or both of the Empatic constituents and most commonly included headache, insomnia, nausea or dry mouth. There were no serious adverse events that were attributed by investigators to Empatic.
We recently submitted to the FDA the results of this trial at 24 weeks, the primary endpoint of the trial. In subsequent correspondence, the FDA confirmed the design of our next planned Phase IIb clinical trial. We plan to initiate this trial in the second quarter of 2008. This trial will be designed to evaluate Empatic against individual monotherapies and placebo. Based on the above results of our completed Phase IIb clinical trial, we expect to take the highest dose ratio of Empatic, and possibly one lower dose ratio, into this upcoming clinical trial.
Empatic employs a proprietary formulation of two CNS molecules, bupropion and zonisamide, that have been independently approved by the FDA in other indications. Bupropion and zonisamide each target reciprocal pathways in the hypothalamus that 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.
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 the later stages of Phase II clinical development. 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," "designed" 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 Empatic, and the potential to obtain regulatory approval for, and effectively treat obesity with, Empatic. 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 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 September 30, 2007 filed with the SEC on November 9, 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.
Orexigen Therapeutics, Inc.
Graham Cooper, 858-436-8600
Chief Financial Officer
GendeLLindheim BioCom Partners
Stephen Gendel, 212-918-4650
Porter Novelli Life Sciences
Jason Spark, 619-849-6005
Posted: January 2008