Orexigen Therapeutics Inc. said the Food and Drug Administration is concerned about the heart side effects of its drug Contrave and will require a new study, a costly undertaking that may prove too burdensome for the small drugmaker.

The FDA’s ruling marks the third rejection of a weight loss drug in recent months, raising questions about whether any new drugs in the class can be made safe enough to win approval. The FDA has not approved a new diet pill in more than a decade.

The FDA request for an additional study suggests the agency may yet approve the drug, but makes that path much more difficult. The news led to a sell-off that wiped out nearly three-quarters of the market value of the company.

Orexigen said it is disappointed with the FDA’s decision and will work with the agency to determine its next step.

“We are surprised and extremely disappointed with the agency’s request in light of the extensive discussion and resulting vote on this topic at the Dec. 7 advisory committee meeting,” said President and CEO Michael Narachi, in a conference call with investors.

Narachi acknowledged that studies of the kind requested by the FDA are normally “fairly large,” and would require the company to raise additional money. Clinical trials to study rare events like heart attack can take years to conduct and cost millions of dollars.

Analysts had viewed Contrave as the most promising of three new diet pills recently submitted to the agency. Contrave is a combination pill, mixing an antidepressant with an anti-addiction drug to curb appetite. Four out of 10 patients taking Contrave for a year lost at least 5 percent of their body weight. Those results narrowly met FDA’s guidelines for effectiveness.

Given the drug’s limited benefit, FDA’s rejection was not surprising, according to drug industry analyst Erik Gordon.

“You have life-threatening possible side effects in return for modest weight loss that might not be produced in the real world — no wonder the FDA wants more data,” said Gordon, a professor and analyst at University of Michigan’s Ross School of Business.

La Jolla, Calif.-based Orexigen does not currently have any products on the market, making Contrave a key to the company’s growth and survival. In trading Tuesday, Orexigen shares tumbled $6.59, or 73 percent, to $2.50.

Analysts expect any obesity drug reaching the market to have the potential to become a billion-dollar seller.

With the U.S. obesity rate for adults nearing 35 percent, the FDA has acknowledged the need for new weight loss drugs. But the agency rejected two other drugs last year due to safety risks, a long-standing issue that has plagued weight loss treatments for decades. Those drugs were made by fellow California drug developers Vivus Inc. and Arena Pharmaceuticals Inc. Both companies have said they plan to resubmit their drugs for approval.

Contrave has been pegged as a more promising treatment because of its relative safety. Unlike the other two drugs reviewed last year, it received a positive vote from the FDA’s panel of outside advisers, who voted 13-7 that the drug’s modest weight loss benefits outweighed its risks.

But the FDA meeting assessing the drug was not free of criticism. FDA scientists and safety advocates complained that the company enrolled few elderly patients or patients with a history of heart disease in its trials, making it difficult to determine the drug’s safety in patients who are likely to need it most.

Heart side effects have been an issue with diet drugs, most notably with Wyeth’s diet drug combination fen-phen, which was pulled off the market in 1997. In October, Abbott Laboratories withdrew its drug Meridia after evidence it increased the risk of heart attack and stroke.

Currently there is just one prescription drug on the market for long-term weight loss: Roche’s Xenical, which is not widely used. Several other generic drugs are approved for short-term weight loss, including phentermine.

Technorati Tags: Contrave, new diet drugs, Orexigen, phentermine, short term weight loss, xenical

The 13-7 vote in favor of Contrave came amid agency concerns that the drug might raise blood pressure in some patients and increase the risk of heart attacks and strokes among some users, according to the Associated Press. But panelists voted 11-8 earlier in the day that those potential health risks could be studied after Contrave was approved.

The FDA does not have to follow the advice of its advisory committees, but it typically does. The agency is expected to make a decision on Contrave by Jan. 31, the wire service reported.

Contrave is manufactured by Orexigen Therapeutics Inc. In October, the FDA voted against approving two other weight-loss drugs, Arena Pharmaceuticals’ lorcaserin and Vivus’ Qnexa, because of safety concerns, according to the AP.

Last July, a study funded by Orexigen and published in The Lancet found that Contrave helped users shed pounds when taken along with a healthy diet and exercise.

People who took the drug for more than a year lost an average of 5 percent or more of body weight, depending on the dose used, the team said.

However, the regimen did come with side effects, and about half of study participants dropped out before completing a year of treatment.

Contrave is combination of two well-known drugs, naltrexone (Revia, used to fight addictions) and the antidepressant bupropion (known by a number of names, including Wellbutrin). The drug appears to boost weight loss by changing the workings of the body’s central nervous system, the researchers said.

The study enrolled men (15 percent) and women (85 percent) from around the country, ranging in age from 18 to 65. They were all either obese or overweightm, with high blood fat levels or high blood pressure.

The participants were told to eat less and exercise, and they were randomly assigned to take a twice-daily placebo or a combination of the two drugs at one of two levels.

After 56 weeks, only about half (870) of the more than 1,700 participants initially enrolled remained in the study. Almost half (48 percent) of those who took the highest dose of naltrexone lost 5 percent of their weight or more, while only 16 percent of those who took placebos did.

However, about 30 percent of those taking Contrave experienced nausea, the study authors say, and other side effects included headache, constipation, dizziness, vomiting and dry mouth.

Still, Contrave may give people struggling to lose weight a new option, the researchers contended.

The Lancet findings echo those of studies into other diet drugs such as Meridia, Xenical and Alli, said Lona Sandon, an assistant professor of clinical nutrition at the University of Texas Southwestern Medical Center in Dallas and spokeswoman for the American Dietetic Association.

“When these are combined with a modestly reduced calorie diet, modest amounts of weight loss are achieved,” she said. “One striking thing to note is the study drop-out rate of 50 percent. This may have been due to side effects of medications, the fact that it is hard to stick to dietary changes for 56 weeks, or [the fact that] slow and only modest weight loss did not meet participant expectations.”

Cynthia Sass, a New York City-based nutritionist and author, added that drugs used to treat addiction also appear to help with weight control, supporting “the notion that food can be addictive for many people.”

An accompanying Lancet editorial noted that one concern is that blood pressure did not drop as much as expected in the higher weight-loss group. “More data are needed to get a better overall assessment of cardiovascular risk of this otherwise promising combination therapy for obesity,” wrote Professor Arne Astrup, a nutrition expert at the University of Copenhagen, Denmark.

Technorati Tags: anti-addiction medication, antidepressant, Contrave, Orexigen Therapeutics, weight loss pill, xenical

Liraglutide, marketed as Victoza, outperformed the established anti-obesity drug orlistat, commercialised as Alli or Xenical, among 564 European volunteers, it suggests.

The 135 men and 429 women volunteers were divided into three groups.

One received daily liraglutide at four different dosages; the second received orlistat; and the third were given a harmless lookalike called a placebo.

In the fortnight before the trial, all the volunteers began a regime that combined daily exercise with a cut in calorie intake by 500 calories.

By comparison, 500 calories is roughly a quarter of the recommended daily energy intake for women, and about a fifth of the recommended intake for men.

Five months later, the liraglutide patients had each lost between 4.8 and 7.2 kilos (10.5 and 15.8 pounds) on average depending on the dosage; the orlistat volunteers had lost 4.1 kilos (9.0 pounds); and the placebo group 2.8 kilos (6.1 pounds).

Seventy-six percent of the high-dosage liraglutide takers lost more than five percent of their weight, compared with 44 percent in the orlistat group and 30 percent in the placebo group.

There was also a big reduction in “prediabetes” conditions among the liraglutide group.

Liraglutide was “well-tolerated,” according to the study.

“Nausea and vomiting occurred more often in individuals on liraglutide than in those on placebo, but adverse events were mainly transient and rarely led to discontinuation of treatment.”

Liraglutide, which is administered into the skin through an injector, was initially developed as a treatment to control blood glucose levels for patients with Type 2 diabetes.

But one of its impacts is to brake the emptying of the contents of the stomach into the intestine, thus prolonging a feeling of satiety.

The study was led by Arne Astrup, a professor of nutrition at the University of Copenhagen. He is also an advisor to liraglutide’s manufacturers, the Danish company Novo Nordisk A/S. The study data was vetted by The Lancet, a peer-reviewed journal.

The authors say the results offer “a new mode of action” for treating obesity, for which only a few effective and safe drugs are available.

Obesity has reached epidemic-level proportions in many rich economies as well as in fast-growing emerging countries.

Over the past 20 years, the rate of obesity has tripled and is more than 30 percent in some European countries, according to an estimate published last year.

Volunteers in the study had a body mass index (BMI) of between 30 and 40. A BMI — one’s weight in kilos divided by one’s height in metres squared — that is above 30 is generally categorised as obese.

Technorati Tags: alli, diabetes drug, Liraglutide, low-fat diet, orlistat, Victoza, xenical