OREXIGEN(TM) Therapeutics Reports Detailed Results of Phase IIb Trial of Empatic(TM) to Treat Obesity
"We believe these trial results further validate the early and sustained weight loss profile that may be achieved with Empatic over the first 24 weeks of therapy," said Orexigen President and CEO, Gary Tollefson, M.D., Ph.D. "Perhaps more importantly, we believe this trial demonstrated a substantial improvement in Empatic's tolerability. We feel this improvement is attributable to our novel and proprietary sustained release (SR) formulation of zonisamide. This tolerability profile improvement is important because it may allow more patients to have the opportunity to realize the potential weight loss benefits of Empatic."
This randomized, double-blind, placebo-controlled trial was the Company's first large, multi-center trial of its novel 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. Each of the six Empatic groups experienced weight loss that was statistically significantly greater than seen with placebo. As previously reported, patients in the intent to treat group receiving the highest dose ratio (360/360 mg) experienced average weight loss of 8.6% from baseline (compared to 1.1% weight loss from baseline for patients on placebo). Among patients completing the first 24 weeks of the trial, the highest dose group achieved a 10.3% weight loss from baseline (compared to 1.2% weight loss from baseline for patients on placebo).
Results of this trial also indicated that Empatic was safe and generally well tolerated. Nearly 80% of subjects completed the trial. The rates of discontinuation due to adverse events for all Empatic patients in the trial (14.0%) and the highest dose group (16.9%) were not significantly different than the 9.1% reported with placebo. Moreover, this overall rate was meaningfully lower than the rate seen in Empatic patients in the Company's previous trial employing an immediate-release form of zonisamide (37.3%). Adverse events were consistent with the existing package labels for one or both of the Empatic constituents and most commonly included headache, nausea, insomnia, anxiety or dry mouth.
The results, by trial arm, are detailed as follows: -0-
Dosage Weight loss @ 24 Discontinuations weeks --------------------------------------------- Bupropion SR Zonisamide SR Intent- Completers Due to AE to- treat ------------ ------------- ------- ---------- ---------------- Group 1 280mg 120mg 4.5% 5.3% 10.3% Group 2 360mg 120mg 6.4% 7.3% 9.2% Group 3 280mg 240mg 6.6% 7.2% 10.0% Group 4 360mg 240mg 6.2% 7.4% 20.7% Group 5 280mg 360mg 7.3% 8.3% 16.9% Group 6 360mg 360mg 8.6% 10.3% 16.9% Group 7 Placebo Placebo 1.1% 1.2% 9.1%
In addition, the trajectory of weight loss for all treatment arms continued downward through 24 weeks without evidence of a plateau. This downward slope was particularly pronounced in the highest dosage group.
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. 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 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 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.
Graham Cooper, 858-436-8600
Stephen Gendel, 212-918-4650
Jason Spark, 619-849-6005
Posted: October 2007