Stock Chart for Orexigen Therapeutics Inc (OREX) 
 
 Orexigen Therapeutics Inc.’s success in winning the first U.S. panel recommendation for a long-sought prescription diet pill led its shares to almost double and shows the company benefited from its rivals’ earlier difficulties. 
 
 Outside advisers to the Food and Drug Administration said weight-loss benefits of Orexigen’s product, Contrave, exceed the dangers of elevated pulse and blood pressure and that a large study on cardiovascular risk can wait until after the drug is approved. The FDA delayed competing treatments from Arena Pharmaceuticals Inc. and Vivus Inc. in October after they failed to win panel backing on safety. 
 
 “The fact that they were able to convince the panel not only that the cardiovascular study can wait, but that the drug can be approved, is exciting, particularly after we saw the other obesity drugs voted down,” Joshua Schimmer, a Leerink Swann analyst, said yesterday in a telephone interview. “It’s hard to know to what extent their strategy was altered by the first two, but it sure as heck didn’t hurt.” 
 
 While the FDA isn’t obliged to follow recommendations of advisers, their support eases concern that had caused Orexigen shares to drop more than a third this year. The La Jolla, California-based company gained from watching the FDA’s safety focus and saw that a commitment to minimize risks and conduct more studies would be needed for approval, Schimmer said. 
 
 Stocks Surge 
 
 Orexigen rose $4.01, or 84 percent, to $8.77 at 4 p.m. New York time in Nasdaq Stock Market composite trading, the most in a single day since the shares began trading in April 2007. Options traders placed record bets on Orexigen last week, saying a positive panel vote would double the company’s value. Vivus shares gained $1.20, or 15 percent, to $9 as analysts said the Orexigen recommendation suggests the long-term heart risks with Vivus’s drug, Qnexa, won’t need to be studied before approval. Arena jumped 16 cents, or 11 percent, to $1.57. 
 
 About 68 percent of American adults are overweight, raising their risk of diabetes, heart disease, high blood pressure and cancer, according to the 2008 National Health and Nutrition Examination Survey. Almost 34 percent are obese, measured as a ratio between height and weight. 
 
 The three companies and their partners have been in a race to introduce the first prescription weight-loss pill in more than a decade. Basel, Switzerland-based Roche Holding AG’s Xenical, approved in 1999, is the only long-term medicine for weight loss since Abbott Park, Illinois-based Abbott Laboratories’ Meridia was pulled off the market in October because of heart risks. 
 
 January Deadline 
 
 Orexigen and partner Takeda Pharmaceutical Co., of Osaka, Japan, are scheduled to receive a decision from the FDA by Jan. 31. Schimmer said approval may be delayed while the company and the agency work out details of the prescribing information and the new study. He expects Contrave and Qnexa ultimately to win approval with potential sales of each reaching $1 billion or more in the U.S. 
 
 “We learned about the complex issues surrounding obesity therapeutics that are important to the FDA and the medical community, and we did our best to address those issues,” Orexigen Chief Executive Officer Michael Narachi said yesterday after the vote. 
 
 Vivus, based in Mountain View, California, said Oct. 29 that it plans to respond within six weeks to the FDA’s request for more information about heart risks and birth defects linked to Qnexa. This would trigger a new two- to six-month review. 
 
 “Vivus is encouraged by Tuesday’s advisory committee meeting because it provides hope for patients that new medical treatments for obesity are seriously being considered by the FDA,” the company said today in an e-mail. 
 
 Arena’s Lorcaserin 
 
 San Diego-based Arena said Oct. 25 that the FDA had questions about tumors seen in studies of rats taking the diet drug lorcaserin, which Arena is developing with Eisai Co. of Tokyo. The companies will meet with the agency later this month. 
 
 “Arena is pleased to see the recognition of the need for obesity medications,” the company said in an e-mail today. “At this time, the company is focused on obtaining FDA approval of lorcaserin as quickly as possible.” 
 
 Contrave, Orexigen’s first product, is a combination of two approved drugs that target different parts of the brain that influence appetite and cravings. The pill contains bupropion, an antidepressant also used to quit smoking, and naltrexone, a treatment for alcohol and painkiller addiction. 
 
 Study Results 
 
 Two tablets of Contrave twice a day helped twice as many patients in studies lose at least 5 percent of their weight compared with a placebo after 56 weeks. The drug missed the FDA’s second standard of effectiveness in failing to show at least a 5 percent benefit over placebo. Patients on the drug also had higher pulse and blood pressure than patients on placebo, even after losing weight. 
 
 Dissident members of the advisory panel said Contrave shouldn’t be approved without a large study of heart risks because it counteracts some of the expected benefits of weight loss, a signal that it may have long-term complications. 
 
 “This drug resembles sibutramine,” said panel member Sanjay Kaul, using the chemical name for Meridia. “There is an opportunity for us to learn from history or else we’re going to repeat it. We need to make sure we get it right this time.” 
 
 Kaul is the director of fellowship training in cardiovascular diseases at Cedars-Sinai Medical Center in Los Angeles. 
 
 To contact the reporter on this story: Catherine Larkin in Washington at clarkin4@bloomberg.net. 
 
 To contact the editor responsible for this story: Reg Gale at rgale5@bloomberg.net. ||||| SILVER SPRING, Md. -- An FDA advisory committee has voted 13-7 that the modest weight-loss benefits of an investigational combination of naltrexone and bupropion (Contrave) outweigh the drug's blood pressure risk. 
 
 The bupropion naltrexone combo is the last in a trio of new weight-loss drugs that went before FDA panels this year, striving to be the latest treatment in the dwindling field of medications to fight obesity. The previous two drugs, phentermine/topiramate (Qnexa) and lorcaserin hydrochloride (Lorqess) were both rejected by the FDA after they fared poorly at advisory committee meetings. 
 
 But Tuesday's advisory committee ended very differently than the previous two. 
 
 Bupropion/naltrexone appeared to offer fewer side effects than the previous two drugs, although it also doesn't appear to work as well at helping obese patients lose weight. 
 
 The FDA will make an approval decision by Jan. 31. The agency does not have to follow the advice of its advisory committees, but it often does. 
 
 Orexigen, the company that makes naltrexone/bupropion in partnership with Takeda, is seeking approval for treatment of obesity and weight management in patients with a body mass index of 30 or above, or 27 or above and with one or more risk factors (e.g., diabetes, dyslipidemia, or hypertension). 
 
 Contrave combines an antidepressant and an anti-addiction drug, both of which have been used individually for 20 years -- naltrexone for opioid addiction and alcohol dependence and bupropion for depression and smoking cessation. However, little is known about combining the drugs for weight managment. 
 
 The Endocrine and Metabolic Drugs Advisory Committee reviewed results from Orexigen's four placebo-controlled, one-year, phase III clinical trials, which enrolled 3,200 obese patients with at least one comorbid condition, including diabetes and depression. 
 
 In all four trials, patients on the naltrexone/bupropion combination lost more weight than those in the placebo group (P<0.001), and more than 30% lost at least 5% of their body weight, which is one standard by which the FDA judges efficacy of weight-loss drugs. 
 
 In a pooled analysis, naltrexone/bupropion patients lost an average of 4.2% more weight than the placebo group (ranging from 3.3% to 4.8%). That falls short of the other FDA standard that after one year, the difference in mean weight loss between the active and control groups should be at least 5%. 
 
 In one trial where patients taking naltrexone/bupropion were compared with those undergoing a lifestyle modification program, the difference between the groups was even smaller, suggesting that diet and exercise can achieve similar results as naltrexone/bupropion. 
 
 "As far as efficacy goes, I think they made it by the hair of their chinny chin chin," said Melanie Coffin, the panel's patient representative. 
 
 In the FDA's assessment of the drug released last week, reviewers expressed concerns over several side effects -- a potential increased risk for dizziness, nausea, seizures, and high blood pressure among patients taking naltrexone/bupropion. 
 
 However, the panel was mostly just concerned with one side effect: The drug's effect on blood pressure. 
 
 In the trials, patients taking naltrexone/bupropion were more likely to have an increase in blood pressure and heart rate than placebo patients, an effect that was most pronounced during the first eight weeks of treatment. 
 
 However, patients taking naltrexone/bupropion who lost at least 5% of their body weight achieved lower blood pressure and heart rate compared with those who lost less weight. But the most impressive improvements in blood pressure and weight loss were seen among patients taking placebo who achieved more than a 5% weight loss, suggesting diet and exercise is the best option for obese patients to lower their blood pressure. 
 
 Panelists were concerned that a drug that is supposed to reduce obesity -- and hopefully other comorbidities along with it -- actually raised blood pressure instead. 
 
 "This is my biggest concern," said Lamont Weide, MD, PhD, chief of diabetes and endocrinology at Truman Medical Centers Diabetes Center in Kansas City, Mo. "That we are blunting all the good effects that we should see with weight loss." 
 
 The FDA reviewers concluded there wasn't enough data on the cardiovascular risks of the drug. The panel seemed to agree, but voted 11-8, with two panelists abstaining, that the company could submit new data after approval to show that the drug doesn't present major heart risks. 
 
 The panel's one neurologist, Michael Rogawski, MD, PhD, said he thought the panel downplayed the drug's seizure risk. 
 
 Two patients in the clinical trials experienced seizures after going on naltrexone/bupropion; no participants in the placebo group had seizures. About one in 1,000 patients who take the drug would be expected to have a seizure, the panelists said. 
 
 "They occur only in one out of 1,000, but still, the consequences of having a seizure could be catastrophic," said Rogawski, who ended up voting in favor of the drug. 
 
 There is currently just one anti-obesity drug on the market: Orlistat (Xenical, Alli), after Abbott, the maker of another drug sibutramine (Meridia) voluntarily agreed to remove it from the U.S. market in October because of increased risk of stroke and MI. 
 
 Several physicians and other healthcare professionals contacted by MedPage Today/ABC News were pleased with the panel's decision and said that doctors badly need a new drug to help patients battle obesity. 
 
 "It is nice to have a medication that can help those who are watching their diet and boosting activity lose the weight that thus far has been a slow process," said dietitian Connie Diekman, director of University Nutrition at Washington University in St Louis. "This is one more option in the tool chest to deal with the obesity issue." 
 
 "Finally!" said Robert F. Kushner, MD, professor of Medicine at Northwestern University Feinberg School of Medicine. "I fully endorse the panel's vote. The key will be to educate physicians on how to best prescribe the medication -- identify patients who will benefit from the medication and to accompany it with lifestyle and behavioral recommendations." 
 
 Paul L. Doering, a pharmacy professor at the University of Florida, said he doesn't "doubt for a minute that this drug will be wildly successful, at least at first," adding, "Time will ultimately tell if it is a good drug or not. In the meantime, I'm going to let somebody else be the first to take it." 
 
 This article was developed in collaboration with ABC News.
– A rarity in the weight wars: An FDA advisory panel gave the green light today to a diet pill that could become the first such drug to hit the market in more than a decade. The FDA is expected to make a final decision next month on Contrave, though it generally follows the advice of its panels. Made by Orexigen Therapeutics—whose shares were soaring, notes Bloomberg—Contrave has what MedPage Today describes has "modest" weight-loss effects. Panel members thought the benefit outweighed potential side effects such as high blood pressure. Contrave is a combination of two drugs already on the market: bupropion, an antidepressant also used to quit smoking, and naltrexone, which is used to treat addictions to alcohol and painkillers. One pharmacy professor tells MedPage Today he's sure it will be a huge success initially. "Time will ultimately tell if it is a good drug or not," he adds. "In the meantime, I'm going to let somebody else be the first to take it."