Contrave Rejection and Obesity Drugs’ Future
Feb01

Contrave Rejection and Obesity Drugs’ Future

Today's a somber day for anyone looking to develop a weight-loss medication. Orexigen's potential obesity drug Contrave has failed to win FDA approval, just as Arena's Lorqess and Vivus's Qnexa before it. In other words, none of the big contenders in the diet drug race we've been covering for nearly a year has panned out. Contrave came into FDA decision-day with a a glimmer of hope behind it. Last December, an FDA panel voted in favor of approving Contrave, though they recommended that Orexigen conduct a clinical trial after approval to track the drug's cardiovascular risk. In contrast, Lorqess and Qnexa hadn't gotten a thumbs-up from the panel. But the agency turned out to be more conservative than its advisory panel. In a so-called Complete Response Letter, FDA told Orexigen it needed to conduct that cardiovascular clinical trial BEFORE Contrave could be approved, not after approval. Orexigen's stock fell over 70% on the news this morning. "Such a study would be huge, expensive, and would take years, and the request probably means that Contrave will never hit the market," writes Forbes's Matthew Herper. So where do we go from here? I hesitate to say that the obesity drug field is dead. We'll certainly continue to see scholarly papers about promising new obesity drug targets. But on the clinical side, the focus is going to have to shift away from weight loss to treating the conditions that tend to go hand-in-hand with obesity, like diabetes. That's what could help tip the safety-efficacy balance in a way that leads to new drug candidates being approved by FDA. This is not a new idea- for instance, C&EN contributing editor Aaron Rowe has covered companies' efforts to mimic bariatric surgery's beneficial effects on diabetes with a pill. Pfizer is in Rowe's story with a potential diabetes drug in clinical trials. The molecule targets an enzyme that reassembles triglycerides. One of its entries at clinicaltrials.gov says it all: "It is anticipated that PF 04620110 will have anti diabetic effects through inhibition of intestinal triglyceride absorption and potentially weight loss." Pfizer exited obesity drug research in 2008. But it didn't abandon efforts to treat some of the conditions that make obesity unhealthy. If targeting a certain enzyme happens to help with both diabetes symptoms and weight loss, so much the better. But weight loss isn't the top...

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Good News for Contrave, Qnexa Could Be Next
Dec08

Good News for Contrave, Qnexa Could Be Next

Apparently, third time’s a charm in the obesity drug world. Yesterday afternoon, an FDA advisory panel recommended approving Contrave, an obesity pill being developed by Orexigen Therapeutics and Takeda. The positive vote came just months after two other obesity drugs, Vivus’ Qnexa and Arena Pharmaceutical’s Lorqess, were rejected. There are plenty of caveats to the good news. First, FDA doesn’t always follow the advice of its advisory committees, although most analysts seem confident Contrave will make it onto the market. But Orexigen and Takeda will likely need to conduct a large, post-approval study to track cardiovascular issues, the details of which would be hammered out with FDA. Second, excitement over the next pill for obesity should be tempered with the reality that Contrave has shown only minimal weight loss. Contrave is a combination of two already-approved drugs, the antidepressant buproprion and the addiction treatment naltrexone. All that said, Orexigen stands to collect more money from Takeda if Contrave makes it to the finish line. Takeda paid just $50 million upfront to license the obesity drug, and will take on the lion’s share of the costs of a post-approval study. The thumbs up for Contrave could also be good news for Vivus’ Qnexa, also a combination of two existing drugs (phentermine and topiramate). In July, an FDA advisory committee, concerned about the lack of long-term safety data for the drug, voted against its approval. FDA backed up that decision in October, issuing a complete response letter (its version of a rejection) citing birth defect worries and cardiovascular risks. But yesterday’s panel was mainly focused on the cardiovascular risks associated with Contrave, and Qnexa is a cleaner drug on that front. One panel member, University of California, Davis, neurologist Michael Ragowski, even said he’d rather prescribe Qnexa versus Contrave. Vivus plans to submit a formal response to the CRL later this month, and FDA would provide its feedback in January. If all goes well, Vivus could gain approval for Qnexa in the second half of 2011, analysts say. Investors seemed optimistic on its chances, as Vivus' stock is up over 20% in pre-market trading. Orexigen is holding a conference call at 4:15pm this afternoon, to discuss the panel. If anything interesting comes out of it, we'll be sure to update...

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Orexigen And Takeda’s Contrave To Face FDA’s Panel Tuesday
Dec03

Orexigen And Takeda’s Contrave To Face FDA’s Panel Tuesday

Today FDA released its briefing documents for Orexigen and Takeda's experimental obesity drug Contrave. And they've got more than one news outlet wondering whether the third time will be the charm in the obesity drug race. On Tuesday, FDA's outside advisers will meet to review the potential drug and make recommendations on whether to approve it. You can read our ongoing coverage of Contrave as well as Arena's Lorqess and Vivus's Qnexa, the other two obesity drug candidates FDA reviewed, here. At first glance, the documents don't contain any big surprises in terms of safety or efficacy. And Orexigen's had time to learn from what happened at the Lorqess and Qnexa panel meetings. That said, Adam Feuerstein makes an interesting comparison- to Meridia, Abbott Labs' diet pill that was pulled from the market this fall because of its cardiovascular risks. We've known that Contrave can raise blood pressure, but the memory of Meridia may influence some of FDA's outside experts. Contrave's cardiovascular risk profile somewhat resembles Abbott Lab's Meridia, which was recently pulled off the market after a September advisory panel meeting. Eight of the 10 experts who will be reviewing Contrave Tuesday voted to recommend Meridia's withdrawal from the market due to the drug's cardiovascular risks. These eight experts are the people Orexigen needs to be most worried about Tuesday. An analyst at Rodman & Renshaw in New York had similar concerns in an interview with Bloomberg. “They may have to do a thorough cardiovascular study before approval,” said Elemer Piros, an analyst at Rodman & Renshaw in New York, in a telephone interview today. “The clear precedent is Meridia. It’s so fresh in our minds that I don’t think the FDA wants to embark on a public experiment in an uncontrolled setting without this information.” So if more studies will be needed, it's a good sign that Leerink Swann analysts Joshua Schimmer and Steve Yoo are impressed with Orexigen's long-term safety strategy, according to a note sent to investors. While no FDA panel is without risk and the track record of obesity drugs at the Endocrine Division is unquestionably poor, we have been impressed with OREX's strategic approach to tackling Contrave's safety-issues head on and its rational explanation for a post-approval study commitment. That's important because at least some of what sank Vivus's Qnexa at its FDA advisory panel evaluation was a desire for more long-term data. But at the end of the day, panelists who voted ‘no’ felt like more long-term safety data was in order. From Feuerstein’s liveblog: one of the “no” votes says obesity is a chronic disease, so tell me what happens to...

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Orexigen Partners With Takeda for Potential Obesity Drug Contrave
Sep02

Orexigen Partners With Takeda for Potential Obesity Drug Contrave

This morning Orexigen Therapeutics became the second of the three leaders in the obesity drug race to partner with a larger company. They've successfully courted Takeda, which now gets exclusive marketing rights to obesity drug Contrave in the U.S., Canada, and Mexico, if the drug gets regulatory approval. Orexigen's shares soared on the news, first released in the pre-dawn hours this morning. In the deal, Orexigen gets $50 million upfront from Takeda and could nab up to $1 billion more, depending on whether Contrave meets certain regulatory and sales milestones. Further details about the agreement are available on an Orexigen press release. Contrave refresher: Contrave is a combination of two drugs already on the market: naltrexone, which is typically used to manage alcohol or opioid dependence, and the antidepressant bupropion. Orexigen’s developed a sustained-release formulation of those active ingredients. This is thought to alleviate the nausea that cropped up in clinical trials, but also could come in handy in terms of real-world prescriptions if the drug is approved. People might want to save money by taking the generic versions of Contrave’s two components but it isn’t clear how that would work for them. In July we covered the first partnership deal in the obesity drug race, that of Eisai and Arena Pharmaceuticals, which is developing the obesity drug candidate lorcaserin. It's worth stepping back to compare and contrast the deals. At a glance, much looks the same. U.S.-based biotech company developing a potential obesity medication partners with a company based out of Japan. Biotech gets $50 mil upfront, with a tantalizing promise of more if certain milestones are met. But Arena's press release about the Eisai deal contains a few more specifics about pricing. I don't see comparable language in the Orexigen release. From Arena's release: Under the terms of the agreement, Arena will receive an upfront payment of $50 million from Eisai and, upon regulatory approval and the delivery of product supply for launch, up to an additional $90 million in milestone payments. Arena will sell lorcaserin to Eisai for a purchase price starting at 31.5% of Eisai's annual net product sales, and the purchase price will increase on a tiered basis to as high as 36.5% on the portion of annual net product sales exceeding $750 million. Arena is also eligible to receive $1.16 billion in one-time purchase price adjustment payments based on annual sales levels of lorcaserin and up to an additional $70 million in regulatory and development milestone payments. John Carroll of FierceBiotech noticed something's been missing from the obesity drug deals: U.S. companies. Noticeably absent from the deal-making are the U.S. pharma companies, several...

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Orexigen’s Obesity Drug Candidate Contrave Gets 12/7 FDA Review Date
Jun23

Orexigen’s Obesity Drug Candidate Contrave Gets 12/7 FDA Review Date

Mark December 7, 2010 on your obesity drug watch calendar. Orexigen Therapeutics has just announced that on that date, an advisory committee at FDA is tentatively set to review the company's new drug application for its obesity drug candidate, Contrave. Symbolically, I can imagine folks might've preferred a different date. December 7, is, after all, best remembered as a day that will live in infamy. But the December date is good for Orexigen in other ways. It's much later than July 15, when FDA is set to evaluate Vivus's experimental obesity drug Qnexa. We've already written about Orexigen's opportunities to learn from its competitors. Here's more of what we've written before about Contrave. Contrave, like Qnexa, is a combination of two drugs already on the market, bupropion and naltrexone. As we explained in 2009, Orexigen’s developed a sustained-release formulation of those active ingredients. This is thought to alleviate the nausea that cropped up in clinical trials, but also could come in handy in terms of real-world prescriptions if the drug is approved. People might want to save money by taking the generic versions of Contrave’s two components but it isn’t clear how that would work for...

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