Orexigen Therapeutics Inc. is anxious to see its obesity medicine Contrave (naltrexone SR/bupropion SR) reach the market after watching two competitors pass by in the neck-and-neck race to bring the first novel obesity medicines to market in 13 years. The NDA for Contrave has been stalled at FDA after the agency required Orexigen to conduct a cardiovascular outcomes study in 2011 Also see "Losing The Battle Of The Bulge: FDA Holds Up Orexigen's Contrave" - Pink Sheet, 1 February, 2011..

But the company announced some progress Jan. 7 on a proposal that will get the PDUFA clock for the application ticking a little faster. In response to Orexigen’s formal Dispute Resolution Request, The Center for Drug Evaluation and Research’s Division of Metabolism and Endocrinology Products has proposed a resubmission procedure that will allow Orexigen to resubmit the NDA based on the summary report of the ongoing cardiovascular outcomes study, LIGHT, as long as the complete clinical study report for the interim analysis is supplied to the FDA within 60 days of the submission.

It was proactive steps by Orexigen that opened the timing door a crack. The company filed a dispute resolution request to the CDER director’s office asking that Contrave be considered for approval on the basis of existing data, with the interim CV outcomes data to be submitted shortly after approval. The company didn’t win that appeal, but did gain a little additional time.

That guidance could position the Contrave NDA resubmission for the second half of 2013, putting the drug on track for a potential approval six months later in early 2014, depending on the timing of the data. The formal announcement is in line with what management has been guiding in recent discussions with investors Also see "Orexigen Eyes Earlier Resubmission Of Contrave NDA" - Pink Sheet, 22 October, 2012..

But first Orexigen needs the interim data from LIGHT to turn out positively in favor of Contrave. The data will become available after at least 87 major adverse cardiovascular events (MACE), making the timing difficult to predict. However, Orexigen is targeting an event rate of around 1.5% annually based on a study population of 9,880; the company calculates that the 87^th event should occur in the second half of 2013. The trial was initiated in June 2012.

Orexigen In Partnering Talks For Rest-Of-World

The data from LIGHT will not only serve as the basis of the NDA resubmission, but will also inform partnering discussions. Orexigen is looking to sign an ex-North America commercial partner for Contrave. The company is already partnered with Takeda Pharmaceutical Co. Ltd. on Contrave in the U.S. in a deal dating to September 2010 [See Deal].The Japanese pharma paid $50 million upfront for rights to market the drug in the U.S., Canada and Mexico. The company will handle the marketing and cost of commercialization and pay Orexigen tiered royalties that begin at 20% of sales. Orexigen retained a co-promote option as well, but hasn’t decided whether or not it will exercise it.

The company is in partnering talks with big pharmas and regional companies, CEO Michael Narachi said in an interview. But he added, “Obviously it is easier to manage if we have a single rest-of-world player along with Takeda.” He said Takeda has also expressed interest in the rest-of-world rights and they are a potential partner as well, particularly since their 2011 acquisition of Nycomed.

The company has plenty of cash on hand to see it through to the interim study results and the signing of a potential partner. Orexigen completed a follow-on public offering in October, raising net proceeds of approximately $56.5 million, with the company announcing in its third quarter financials that it expects to end the year with cash and equivalents of between $130 million to $135 million.

“It was important to us to add a little bit to the balance sheet when we did the recent financings because we are going to be negotiating a rest-of-world transaction with the data from the LIGHT study, and we wanted to have sufficient runway at that time,” Narachi said.

Orexigen also said it remains on track to initiate the Ignite study, a randomized open-label clinical trial designed to study the weight loss potential of Contrave therapy in the real-world setting, along with a commercially available comprehensive lifestyle intervention program versus usual care. The company plans to initiate the trial in the first quarter of 2013 and enroll approximately 200 patients.

“People have so far had a hard time understanding the real-world promise of obesity therapeutics,” said Narachi. “The goal of the Ignite study is to enroll what we believe would be on label and representative population and also use the product in a way that we believe it would or should be used commercially.” That means studying the drug with a commercial behavioral modification program. The study will evaluate patients for 16 weeks before the data is unblinded. Responders will be able to continue therapy at week 16.

Orexigen hopes the data will help build a case for Contrave in what has been a difficult commercial market for obesity drugs and what could be even more difficult for Contrave given that it will be the third new obesity drug on the market. Arena Pharmaceuticals Inc.’s Belviq (lorcaserin) and Vivus Inc.’s Qsymia (phentermine/topiramate) were approved back-to-back on June 27 and July 17, respectively. Belviq has yet to launch as the drug is awaiting drug scheduling by the Drug Enforcement Agency; Arena expects to launch it in early 2013 Also see "Belviq Gains FDA Approval For Weight Loss, But DEA Review Will Delay Launch" - Pink Sheet, 28 June, 2012.. Vivus launched Qsymia in mid-September, but so far the drug has yet to gain serious traction, with uptake hindered by reimbursement hurdles and the company has largely had to navigate the cash-pay market ([A#00121210010]).

Orexigen Defines A Way To Get The Contrave PDUFA Clock Ticking

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