UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, DC 20549

FORM 8-K

CURRENT REPORT

Pursuant to Section 13 or 15(d) of the

Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): September 20, 2011

OREXIGEN THERAPEUTICS, Inc.

(Exact Name of Registrant as Specified in its Charter)

Registrant’s telephone number, including area code: (858) 875-8600

(Former Name or Former Address, if Changed Since Last Report.)

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instruction A.2. below):

On September 20, 2011, Orexigen Therapeutics, Inc. (the “Company” or “Orexigen”) announced that following a recent meeting with senior officials in the U.S. Food and Drug Administration’s (the “FDA”) Office of New Drugs (“OND”), the Company received written correspondence detailing OND’s design requirements for a cardiovascular outcomes trial (“CVOT”) for Contrave^® that would address the Complete Response Letter received in January 2011. Orexigen believes that these design requirements are reasonable and feasible and provide the certainty required to reinitiate development of Contrave. Importantly, FDA stated that “if the interim analysis meets the specified criteria to exclude an unacceptable increased cardiovascular (“CV”) risk, the drug could be approved.” Furthermore, FDA stated that “While we still plan to convene a public advisory committee meeting to discuss topics related to obesity drug development early next year, that meeting will not impact on the advice provided in this letter and the agency will honor the advice provided.”

The most important aspects of the CVOT design outlined by FDA include that the trial be powered based on an intent-to-treat analysis, along with criteria for interpreting the results at interim and final analyses that are similar to those that are applied to diabetes drugs. Specifically, FDA advised that the trial enroll a population of overweight and obese patients with an estimated background rate of 1.0-1.5% annual risk of major CV events. In this population, the upper bound of the 95% confidence interval should exclude a hazard ratio of 2.0 and 1.4 at the interim and final analyses, respectively. Both FDA and Orexigen estimate that such a study would require approximately 87 total events by the interim analysis to enable resubmission of the NDA for approval. Orexigen estimates that the entire study would require less than 10,000 patients and less than two years from study start to the interim analysis. The Company plans to meet with the review division to finalize a protocol with the objective of initiating the CVOT in the first half of 2012, with potential approval in 2014.

Based on this new feedback from FDA outlining a clear and feasible path forward for Contrave, the Company’s three near-term priorities for the program are to: (1) finalize the trial protocol with FDA; (2) re-engage with parties that expressed interest in partnering the ex-North American markets for Contrave; and (3) implement the CVOT as soon as it is able.

Orexigen cautions you that statements included in this report 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 the Company’s current beliefs and expectations. These forward-looking statements include statements regarding: the study design for, and the timing and feasibility of, the CVOT; the potential for resubmission and approval of an NDA based on interim results of the CVOT; the prospects for ultimate approval of an NDA for Contrave; and the potential to complete a partnership or similar transaction for ex-North American rights to Contrave and maintain the Company’s existing North American collaboration with Takeda Pharmaceuticals. 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: Orexigen’s ability to maintain and raise sufficient capital to fund the CVOT and maintain its other operations; the uncertainty of the FDA approval process, including requirements for additional clinical and non-clinical studies or other commitments prior to the submission and approval of an NDA for Contrave; Orexigen’s ability to demonstrate that the risk of major adverse CV events in overweight and obese subjects treated with Contrave does not adversely affect the product candidate’s benefit-risk profile; the potential for FDA’s planned 2012 public advisory committee meeting on obesity drug development to result in additional NDA approval requirements for Contrave as well as post-approval commitments; Orexigen’s dependence on Takeda Pharmaceuticals for aspects of the development and commercialization of Contrave; reliance on third parties to supply Contrave and assist with the development of Contrave and the regulatory submissions related thereto; the potential for adverse safety findings relating to Contrave; intense competition in the obesity marketplace and the potential for new products to emerge that provide different or better therapeutic alternatives for obesity and weight loss compared to Contrave; and other risks described in the Company’s filings with the Securities and Exchange Commission (the “SEC”). 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 report 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 Quarterly Report on Form 10-Q, which was filed with the SEC on August 8, 2011 and is available from the SEC’s website (www.sec.gov) and the Company’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.

SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.