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...

Read More
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...

Read More
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...

Read More
FDA Rejects Vivus’s Obesity Drug Qnexa
Oct29

FDA Rejects Vivus’s Obesity Drug Qnexa

As was widely expected, the Food and Drug Administration has rejected Vivus's experimental weight-loss drug Qnexa, making it the second obesity drug in a week to be turned away by the agency. On Saturday, Arena Pharmaceuticals said it had received a complete response letter (CRL) for  its obesity drug Lorqess (lorcaserin), based largely on worries that the drug caused tumors in rats. The biggest concerns in Vivus' CRL were around birth defects and cardiovascular risk. Vivus had already submitted a plan to keep tabs on pregnancy and birth defects after the drug was approved, and the agency seems to want to continue evolving that monitoring strategy. FDA also wants data showing that the drug's propensity to raise heart rate does not lead to an increased risk of cardiovascular events. If eventually approved, FDA said Qnexa would be considered a controlled substance along the lines of Xanax and Valium. The good news  is that Vivus says it doesn't believe it needs to generate any new clinical data to fulfill FDA's requests. Further, the agency didn't ask any questions about the drug's ability to induce weight loss. In a conference call with investors this morning, Vivus CEO Leland Wilson said it would take the company about six weeks to prepare its response to the CRL, and depending on how FDA classifies the application, the drug could be reviewed two-to-six months after the submission. Shares of Vivus were up over 30% in pre-market trading. As a reminder, Qnexa is the only drug in the three-way obesity race to lack a partner. Arena has licensed Lorqess to Esai, and Takeda has bought into Orexigen's Contrave. Qnexa is a combination of two drugs that are already FDA-approved: it’s a combination of topiramate, an antiseizure medication that enhances feelings of fullness, and phentermine, the “Phen” part of Fen-Phen, which was not linked to heart valve defects. When FDA posted briefing documents in advance of the Qnexa panel meeting, we learned that the agency had no problem with Qnexa's ability to help patients lose weight. But the committee had safety concerns in five areas: effects on pregnant women, cardiovascular risks, psychiatric events, cognitive events, and metabolic acidosis. Last July, an FDA panel thought that Vivus needed more long-term safety data on Qnexa and voted not to recommend the drug for approval. (Seven panel members voted for approval but nine recommended against...

Read More
Abbott Takes Diet Drug Meridia (Sibutramine) Off The Market
Oct08

Abbott Takes Diet Drug Meridia (Sibutramine) Off The Market

A diet pill bit the dust today- the Food and Drug Administration has asked Abbott Laboratories to take its drug Meridia off the market in the U.S. Meridia, or sibutramine, was approved by FDA in 1997, but the company voluntarily pulled Meridia after FDA's request, and is also halting sales of the drug in Canada and Australia. FDA's request was based mostly on a large study from last fall called the SCOUT trial. The trial suggested that patients on Meridia had more cardiovascular events, such as heart attacks and strokes, compared to patients taking a placebo. “Meridia’s continued availability is not justified when you compare the very modest weight loss that people achieve on this drug to their risk of heart attack or stroke,” said John Jenkins, M.D., director of the Office of New Drugs in the FDA’s Center for Drug Evaluation and Research (CDER), in an FDA press release. “Physicians are advised to stop prescribing Meridia to their patients and patients should stop taking this medication. Patients should talk to their health care provider about alternative weight loss and weight loss maintenance programs,” Jenkins said. Meridia was already pulled from the market in the UK and other European nations earlier this year. You can click here to read more about how the drug works. And last month an FDA advisory panel was split as to whether to keep Meridia on the market here in the U.S. Of 16 panelists, 8 voted to withdraw the drug, 2 voted to keep it on the market with more strict warning label language, and 6 voted to keep it on the market with label revisions and restrictions on which doctors can prescribe the drug. The loss of Meridia isn't a big blow to Abbott's stock. Prescriptions for Meridia have already dropped over the years because of safety concerns, from a high of 1.3 million prescriptions in 1998 to 250,000 in 2009, according to FDA. But the next wave of obesity drug news, should it be similarly negative, could take a bigger toll on the companies involved, which are both smaller than Abbott. Mark your calendars for October 22 and October 28- these are the goal dates for FDA to finish reviewing applications for Arena Pharmaceuticals' drug candidate Lorqess and Vivus' Qnexa. FDA panels have recommended against approving both drugs. UPDATED 3:59 PM- to reflect withdrawal of Meridia from Canada and Australia as well as...

Read More