Orexigen Therapeutics Receives Dispute Response Indicating FDA is Highly Supportive of Exploration of a Faster Path to Resubmission of the Contrave NDA

SAN DIEGO, Oct. 22, 2012 /PRNewswire/ -- Orexigen® Therapeutics, Inc. (NASDAQ: OREX) today announced that it has received a response to a formal dispute resolution request (FDRR) from the United States Food and Drug Administration's (FDA) Center for Drug Evaluation and Research (CDER).

The response indicates that CDER highly supports further discussions regarding a faster path to resubmission of the Contrave® (naltrexone SR / bupropion SR) New Drug Application (NDA). Orexigen plans to explore with the FDA the possibility of resubmitting the Contrave NDA in advance of the interim data from the Light Study, the cardiovascular outcomes trial evaluating Contrave. Under this scenario data from the planned interim analysis would be provided during the anticipated review period. Although procedural details need to be addressed, the Company is optimistic that these discussions could result in a faster path to resubmission of the Contrave NDA.

Orexigen also announced that it has surpassed its goal to enroll 7,000 patients in the Light Study and plans to enroll approximately 9,000 patients through the end of 2012. With the resulting increase in observation time in the study, the time to accrual of the 87 major adverse cardiovascular events (MACE) needed to conduct the interim analysis should occur up to two months sooner, potentially as soon as the second quarter of 2013.

"We are encouraged by the ongoing dialogue with the FDA and are happy that FDA recognized the benefit of being prepared to act on Contrave soon after the interim data are available," said Michael Narachi, CEO of Orexigen. "We and our commercial partner, Takeda, are excited that the possibility of an earlier resubmission coupled with higher patient enrollment may result in a reduction in the time to potential approval for Contrave."

Orexigen's FDRR

Orexigen requested that Contrave be considered for approval on the basis of existing data together with a postmarketing requirement to supply the interim cardiovascular outcomes data shortly after approval. CDER denied this request, reaffirming that cardiovascular outcomes data from the interim analysis of the Light Study is required prior to approval; however, CDER indicated that it was highly supportive of the exploration of a faster path to resubmission of the Contrave NDA.

Light Study Enrollment Update

Orexigen has now enrolled more than 7,000 patients into the Light Study. To take advantage of ongoing enrollment momentum and potentially speed the time to the interim analysis, Orexigen is continuing to enroll up to 9,000 patients through the end of 2012.

The primary endpoint of the Light Study is the time to MACE during randomized treatment with Contrave compared to placebo. After at least 87 MACE have been adjudicated, the study's independent Data Monitoring Committee will conduct an interim analysis. The exclusion of a doubling of risk of MACE at the interim analysis was established as the threshold for approvability of Contrave during discussions with the FDA prior to the start of the Light Study. The timing of the 87^th MACE will be dependent upon the observed rate of MACE in the study, which at this time is too early to predict.  With today's recommendation from the FDA, Orexigen will work with CDER to define a path to expedite resubmission in advance of an anticipated completion of the interim analysis, in order to enable a potentially earlier PDUFA date for the Contrave application. 

About the Orexigen – Takeda Alliance

In 2010, Orexigen and Takeda Pharmaceuticals U.S.A., Inc., entered into an exclusive partnership to develop and commercialize Contrave® (naltrexone SR/bupropion SR), Orexigen's investigational drug for the treatment of obesity, in the United States, Canada and Mexico.

Conference call this morning at 8:30 a.m. Eastern Time

Orexigen will host a conference call and webcast this morning at 8:30 a.m. Eastern Time to discuss the Formal Dispute Resolution Response and the Light Study update.

To listen to the conference call, please dial:

A playback of the call will be available beginning today at 11:00 a.m. Eastern Time through November 5, 2012, and may be accessed by dialing:

Additionally, you may access the live and subsequently archived webcast of the conference call from the Investor Relations section of the Company's website at www.orexigen.com.

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 has completed Phase III clinical trials and for which a New Drug Application has been submitted and reviewed by the FDA. The Company has also reached agreement with the FDA on a Special Protocol Assessment (SPA) for the Light Study, the Contrave cardiovascular outcomes trial. The Company's other product candidate, Empatic™, has completed Phase II 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," "should," "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 possibility of resubmitting the Contrave NDA in advance of the interim data from the Light Study, the potential to accelerate resubmission of the Contrave NDA; the timing of patient enrollment and MACE in the Light Study; the ability to enroll the targeted patient population; the ability to enroll approximately 9,000 patients; the potential for, and timing of, the accrual and adjudication of MACE and the potential resubmission of the Contrave NDA; the safety and effectiveness of Contrave; and the potential for, and timing of, approval for Contrave. 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 the Orexigen business, including, without limitation: the possibility that the procedural details are not able to be worked out with the FDA resulting in the inability to resubmit the NDA prior to the receipt of the interim data from the Light Study; 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; Orexigen's ability to conduct the Light Study and the progress and timing thereof, including risks associated with recruiting and enrolling patients in the Light Study; Orexigen's ability to demonstrate in the Light Study that the risk of MACE in overweight and obese subjects treated with Contrave does not adversely affect the product candidate's benefit-risk profile; the potential that earlier clinical trials may not be predictive of future results in the Light Study; the potential for the FDA to not approve Contrave even after the resubmission with the MACE event data; the potential for the Light Study to cost more than what is projected; the potential for early termination of the collaboration agreement between Orexigen and Takeda; the costs and time required to complete additional clinical, non-clinical or other requirements prior to any resubmission of an NDA; the therapeutic and commercial value of Contrave; Orexigen's ability to maintain sufficient capital; and other risks described in the Company'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 Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission August 9, 2012 and which is 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.