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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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...

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What’s Next for Lorqess?
Sep17

What’s Next for Lorqess?

Arena Pharmaceuticals’ obesity drug candidate Lorqess was summarily dismissed by an FDA advisory committee yesterday, leaving many to wonder: what’s next? The panel had few questions about the drug's efficacy, but voted it down in large part due to worrisome data showing high doses of the compound caused tumors in rats. So is there a way forward for Lorqess? Or will it be relegated to the annals of Dead-in-the-Water Obesity Drugs? Analysts have mixed opinions on how Arena could get itself out of this pickle. Some think  the biotech could salvage the drug if it could offer up one key piece of information: the mechanism of action of the tumors seen in rats. In a call with analyst this morning, Arena suggested it had already proven this point, noting that the presentation by Gary Williams, an expert on the mechanisms of carcinogenesis, showed that the rat findings did not translate to humans. “It’s a shame there were no carcinogenicity experts on the panel,” Arena’s president and CEO Jack Lief said. “My view is they were having difficulty understanding our presentation.” The company didn't offer much guidance as to what other data it had on hand or other studies it could conduct to close the book on the issue. Other industry watchers are focused on another issue the panel had: the unrealistic patient population in which Arena chose to test lorcaserin. They thought the people in the trial were not close enough to the kind of folks who would really be taking the drug in the real world--in other words, people with the kind of health complications typically associated with obesity. Later this year, Arena will release data from its BLOOM-DM study, which is meant to test the drug’s efficacy in diabetics. Cowen & Co’s Phil Nadeau suggested that trial may satisfy the agency’s patient population worries. But JPMorgan’s Cory Kasimov was less optimistic about the diabetes data providing reassurance about the drug’s safety. “With only 604 patients randomized to either drug or placebo (not to mention dropouts), it’s just way too small to generate any satisfactory answers,” Kasimov said in a note last night. Not to mention the drug has to show it still works in this tough-to-treat group. BMO Capital analyst Jason Zhang suggested that another path forward would be for Arena to conduct a Phase II proof of concept trial of lorcaserin and phentermine in the right patient population (i.e. diabetics). He thinks the combination should be more effective at helping people shed weight than lorcaserin alone, and notes that data from Arena and academic researchers suggest the duo would not have the same heart  issues that...

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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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