Orexigen Resubmits Contrave New Drug Application

SAN DIEGO, Dec. 11, 2013 /PRNewswire/ -- Orexigen® Therapeutics, Inc. (Nasdaq: OREX) today announced that the Company has resubmitted the Contrave® New Drug Application to the United States (U.S.) Food and Drug Administration (FDA). Investigational drug Contrave (naltrexone sustained release (SR) / bupropion SR) is being developed for weight loss and maintenance of weight loss.

The resubmission follows the November 25, 2013 announcement of the successful interim analysis of the Light Study, the Contrave cardiovascular outcomes trial (CVOT), which is being conducted under a Special Protocol Assessment with the FDA. In January 2011, Orexigen received a Complete Response Letter (CRL) from the FDA detailing a single approval deficiency—the need to conduct a clinical trial of sufficient size and duration to exclude excess risk of major adverse cardiovascular events. In less than three years, Orexigen negotiated with FDA a feasible CVOT design, enrolled the CVOT, and generated safety data responsive to the CRL.

"Resubmitting the Contrave NDA is an exciting moment for Orexigen," said Michael Narachi, CEO of Orexigen. "I am proud of our team and admire their determination to bring Contrave forward to help patients with obesity."

Narachi continued: "This resubmission sets in motion the first of four potential key catalysts in 2014. With the successful Light Study interim analysis, we are confident in the prospect for approvals next year in the United States and in Europe. If Contrave is approved, we look forward to a well-executed U.S. launch by Takeda. Additionally, we anticipate making progress next year in our discussions with potential partners for Contrave for territories outside North America."

By agreement with the FDA, the independent Data Monitoring Committee's summary report of the Light Study interim analysis formed the basis of the resubmission of the NDA. The interim analysis clinical study report (CSR) will be supplied to the FDA within 60 days of the NDA resubmission. The review period for the resubmission is expected to be six months.

About the Light Study
The Contrave Light Study is a double-blind, placebo-controlled cardiovascular outcomes trial that randomized approximately 8,900 patients. The primary objective of the Light Study, which Orexigen is conducting under a Special Protocol Assessment with the FDA at approximately 260 clinical sites in the United States, is to rule out excess cardiovascular risk in overweight and obese patients receiving Contrave. In November 2013 Orexigen announced successful results of the interim analysis of the Light Study, stating that it met the prespecified criteria to exclude a hazard ratio of 2.0, using the upper bound of the 95% confidence interval, for excess risk of major adverse cardiovascular events (MACE) in patients receiving Contrave as compared to placebo.

About Contrave
Contrave (naltrexone sustained release (SR)/bupropion SR) is an investigational medication being evaluated for weight loss and maintenance of weight loss. Prior to initiation of the Light Study, Contrave was studied in clinical trials enrolling more than 4,500 people. In these clinical trials, 53 percent of study participants taking Contrave and 21 percent of those taking placebo lost five percent or more of their body weight over the 12 month trial duration. Many patients saw improvements in cholesterol levels, and blood sugar control. Those who combined Contrave with intensive diet and exercise experienced the most reduction in body weight. There is no guarantee that Contrave will help patients lose weight.

In the Contrave Phase 3 clinical development program, the most frequent adverse events in patients on Contrave were nausea, constipation, headache, vomiting, dizziness, insomnia, dry mouth, and diarrhea. These were mostly mild to moderate in severity.

Orexigen has licensed North American Contrave rights to Takeda Pharmaceuticals. Orexigen owns Contrave rights in Europe and throughout the rest of the world outside of North America and will seek a partner to commercialize Contrave in those territories. In October 2013, Orexigen submitted a Marketing Authorization Application (MAA) for Contrave to the European Medicines Agency (EMA).

About Orexigen Therapeutics

Orexigen Therapeutics, Inc. is a biopharmaceutical company focused on the treatment of obesity. The Company's lead product candidate is Contrave, which the Company is evaluating in the Light Study, a cardiovascular outcomes trial being conducted under a Special Protocol Assessment (SPA) with the FDA. Based on successful results of the Light Study, the Company resubmitted the Contrave NDA to the FDA. The Company's other product candidate, Empatic, has completed Phase 2 clinical trials. Further information about the Company can be found at 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. Words such as "believes," "anticipates," "plans," "expects," "indicates," "will," "should," "intends," "potential," "suggests," "assuming," "designed" and similar expressions are intended to identify forward‐looking statements. These statements are based on the Company's current beliefs and expectations. These forward‐looking statements include statements regarding: the timing of potential approval of the NDA for Contrave in the U.S. and the MAA for Contrave by the European Medicines Agency (EMA); the benefit risk profile for Contrave; and the execution of the Contrave U.S. launch by Takeda; Orexigen's plans to seek a commercialization partner in territories outside of North America; and the timing of the submission of the CSR for the interim analysis. 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 materially from those expressed or implied in this release due to the risk and uncertainties inherent in the Orexigen business, including, without limitation: the possibility that the FDA determines not to initiate review of the Contrave NDA until it has received the CSR for the interim analysis; the SPA is not binding on the FDA if public health concerns unrecognized at the time the SPA agreement was entered into become evident, other new scientific concerns regarding product safety or efficacy arise, or if Orexigen fails to comply with the agreed upon trial protocol; the potential for the FDA to not approve Contrave even after meeting the prespecified threshold and resubmitting the NDA; the possibility that public disclosure of the results of the interim analysis would later be deemed to jeopardize the integrity of the Light Study potentially resulting in the requirement to conduct additional, costly studies; additional analysis of the interim results or new data from the continuing Light Study, including safety-related data, may produce negative or inconclusive results, or may be inconsistent with the conclusion that the interim analysis was successful; the potential that the interim analysis may not be predictive of future results in the Light Study; the potential for early termination of Orexigen's North American collaboration agreement with Takeda; the results from the interim analysis may not be sufficient to satisfy or respond to the Day 120 List of Questions from the EMA or any other data requirements of the EMA in connection with the review of the MAA; even if the NDA is approved by the FDA, the final results of the Light Study may not support continued approval of Contrave; the therapeutic and commercial value of Contrave; and other risks described in Orexigen's 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, and Orexigen undertakes no obligation to revise or update this news release to reflect events or circumstances after the date hereof. Further information regarding these and other risks is included under the heading "Risk Factors" in Orexigen's Current Report on Form 8-K filed with the Securities and Exchange Commission December 2, 2013 and its other reports, which are available from the SEC's website (www.sec.gov) and on Orexigen's website (www.orexigen.com) under the heading "Investor Relations." 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.

SOURCE Orexigen Therapeutics, Inc.