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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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...

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Arena’s Weight-Loss Pill Lorqess (lorcaserin): Waiting For FDA
Oct21

Arena’s Weight-Loss Pill Lorqess (lorcaserin): Waiting For FDA

Tomorrow is the deadline for the Food and Drug Administration to make a decision about whether or not to approve Arena Pharmaceuticals' experimental obesity drug Lorqess (lorcaserin). In advance of the decision I've recapped some Lorqess news and information from the last several months. We will update you when FDA's decision comes in. Of the three potential new diet pills racing to reach the market, Lorqess (lorcaserin) is the only one where the active ingredient is a completely new molecule. Its competition, Vivus's Qnexa and Orexigen's Contrave, are both combinations of drug molecules that have already been FDA-approved for other conditions. Lorqess targets an appetite-suppressing serotonin receptor located in the brain. It's the same receptor that was targeted by fenfluramine, an ingredient in the infamous Fen-Phen obesity drug combo. Fenfluramine was associated with heart valve damage and a fatal lung disorder- it was pulled from the market in 1997. Lorcaserin is different from fenfluramine- it is more selective for the specific subtype of serotonin receptor found in the brain and avoids the one that’s found in the heart. Arena's idea behind Lorqess was that a more selective drug might have the weight-loss benefits with fewer side effects. Arena has had to pay special attention to safety throughout lorcaserin’s development and they haven’t run into heart valve trouble. In July, Arena landed a partner for marketing Lorqess- Japan's Eisai. But last month, when an FDA panel met to discuss Lorqess, the outcome was disappointing for Eisai and Arena. Background materials for the panel session raised questions about malignant tumors that occurred in rats given high doses of lorcaserin. And the panel itself recommended that FDA not approve Lorqess by a 9 to 5 vote. The panel decided not enough data was available to assuage concerns about safety, and was also concerned about how the drug would work in a wider population than was tested during clinical trials. In the aftermath of the panel recommendation, analysts suggested a number of pieces of data that Arena could provide to improve its overall package of information about Lorqess, and thus the drug's chances. But many of the suggestions, which included a detailed study of the mechanism behind the rat tumors, and a Phase II proof of concept trial of lorcaserin and phentermine in diabetics, take years, not months. Today's FDA decision is sure to set the tone for the next couple of months, since Lorqess is the first of the three big contenders to be judged. FDA could decide to ask for more data on Lorqess, or make a decision outright. Stay...

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FDA Panel Thumbs-Down For Arena and Eisai’s Diet Pill Lorcaserin (Lorqess)
Sep17

FDA Panel Thumbs-Down For Arena and Eisai’s Diet Pill Lorcaserin (Lorqess)

Yesterday brought yet another disappointment to the obesity drug development field- an FDA panel recommended rejecting Arena and Eisai's potential diet pill lorcaserin (Lorqess) by a vote of 9 to 5. The message from the panelists was that not enough data was available to assuage concerns about safety, as well as concerns about how the drug would work in a wider population. This marks the second thumbs-down for a prospective obesity drug this year. Vivus's drug candidate Qnexa received a 'no' vote from the panel in July. Going into the yesterday's panel, the mood wasn't exactly sunny. As I wrote yesterday, the FDA briefing documents for lorcaserin contained an unexpected safety surprise. The agency was concerned about malignancies that cropped up in rats taking high doses of lorcaserin. And Arena's stock had tanked on the news. At the panel, Arena tried to allay FDA's concerns right off the bat- in its presentation to the panel, the company said that the tumors were attributable to rat-specific mechanisms, so they wouldn't apply to people. The company even presented a slide listing FDA approved drugs that showed higher rates of rat cancers than lorcaserin (I do not have this information but will update if I get it). The company reiterated that in clinical trials, patients taking lorcaserin did not have an increased risk of cancer. FDA's briefing documents also contained a safety note about heart valve problems. As I've written before, lorcaserin had a lot to prove in this department. It targets the same serotonin receptor as fenfluramine, an ingredient in the infamous Fen-Phen obesity drug combo. Fenfluramine was associated with heart valve damage and a fatal lung disorder- it was pulled from the market in 1997. But lorcaserin is different from fenfluramine- it is more selective for one specific subtype of serotonin receptor and avoids the one that’s found in the heart. Arena had surmised that this would help avoid the valve problems that plagued fenfluramine, and the company has had to pay special attention to heart valve safety throughout lorcaserin’s development. The reason FDA is concerned is that their statistical analysis of Arena's heart valve data (using a different method from Arena) suggests a risk for heart valve damage for patients on lorcaserin. FDA said the company could not statistically rule out a 50% increase in the risk of heart valve problems. At the panel, Arena defended its own data and statistics and said it was committed to continued safety monitoring in a post-approval period. But at the end of the day, it was the safety-efficacy balance that led to the thumbs-down vote from FDA's panel. As I wrote back...

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Waiting For Arena, Thoughts On Meridia
Sep16

Waiting For Arena, Thoughts On Meridia

Today the second of three potential drugs in the weight-loss race is in the hot seat- Arena Pharmaceuticals' lorcaserin, which we recently learned will be called Lorqess, if approved. An FDA panel is meeting to decide whether it will recommend the drug for approval. I'm following two liveblogs of the panel, from Lisa LaMotta of Minyanville and Adam Feuerstein of TheStreet.com, and will post my thoughts on the aftermath tomorrow. Obesity drug watchers are looking for clues about today's panel based on one that happened yesterday- that was when Abbott Laboratories' obesity drug Meridia, on the market since 1997, came under FDA's microscope. Meridia works by blocking reuptake of the neurotransmitters serotonin and noradrenalin in the brain, leading to a decrease in appetite. It's effective at helping patients shed pounds, but the drug also boosts blood pressure and heart rate. So doctors and patients have had to deal with a tradeoff between weight loss efficacy and safety (this theme seems to come up a lot in the obesity drug field). Things shifted last November, when a large study called the SCOUT trial suggested that patients on sibutramine had more cardiovascular events compared to patients on placebo. As this WebMD article puts it: The drug is already not supposed to be used in patients with known cardiovascular disease. But experts said they were troubled that many patients with undiagnosed disease could be at greater risk if they use the drug to lose weight. In the aftermath, sibutramine was pulled from the market in the UK and other European nations. And stateside, concern mounted. Which brings us to yesterday's panel. The panel vote was split as to whether to keep sibutramine on the market. 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. (Hat tip to Shelley Wood at theheart.org for getting the vote results up on Twitter asap). So in short, it's not clear to me what will become of Meridia. As for whether the Meridia panel outcome will affect the Lorqess panel today, Leerink Swann analyst Joshua Schimmer wrote in a note to investors that FDA's safety concerns for lorcaserin/Lorqess are likely to be different than the concerns about sibutramine/Meridia. "Because lorcaserin drops both heart rate and blood pressure (albeit in a non-statistically significant manner), we believe the CV issue will not be a major issue," he wrote. But FDA's briefing documents for Lorqess had a safety surprise, which Schimmer says may come into play....

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