Orexigen Therapeutics, the San Diego-based obesity drug developer, underwhelmed investors back in January with its incremental ability to help patients lose weight. But now the company is presenting more detailed results from a clinical trial that says it had a positive effect on lowering the risk of heart disease while improving patients’ quality of life.
The results of the 793-patient clinical trial, the first of four major studies Orexigen (NASDAQ: OREX) plans to release this year, are being presented today at the American Diabetes Association’s annual meeting in New Orleans.
Orexigen is one of three biotech companies in late-stage development of obesity drugs—along with San Diego-based Arena Pharmaceuticals and Mountain View, CA-based Vivus. Orexigen has lost one-fourth of its market value this year, after it released the first major finding from the study. It reported on Jan. 8 that patients who took its long-lasting combination of naltrexone and buproprion (Contrave), lost an average of 20.3 pounds, or 9.3 percent of their body weight, when they took the drug and followed an intense diet and exercise program. That compared with an average of 11 pounds, or 5.1 percent weight loss, among patients who got a placebo in addition to the diet and exercise. The difference between those groups, 4.2 percentage points, fell short of what the FDA generally considers a meaningful weight loss drug—one that is at least 5 percentage points better than a placebo.
This trial, known as NB-302, did meet a second definition the FDA has established for an effective obesity drug. If twice as many patients lose 10 percent of their body weight on the drug compared with a placebo that can be considered a success, the FDA has said in guidelines to industry. The Orexigen treatment scored on that measurement. About 41.5 percent of patients on the drug lost 10 percent of their body weight, compared with 20.2 percent in the placebo group who did that well.
Any drug that can help people lose significant amounts of weight with a side-effect profile that is squeaky-clean has a chance to be a big seller. Obesity rates in the U.S. have been skyrocketing for years, with about two-thirds of U.S. adults are now considered overweight or obese, putting them at risk for a litany of other conditions like heart disease, diabetes, high blood pressure, and arthritis. The cost to society of all this unhealthy weight gain is hard to measure because it’s intertwined with so many diseases, but a U.S. Surgeon General’s report in 2000 fingered it as responsible for about 9 percent of national healthcare spending.
“It’s clinically significant weight loss, but (Orexigen) is kind of on the edge,” says Xavier Pi-Sunyer, the director of obesity research at St. Luke’s-Roosevelt Hospital in New York, a professor of medicine at Columbia University, and an investigator on the clinical trials of all three major obesity drugs in development from Orexigen, Arena, and Vivus. The weight loss for people on the drug, was “modest,” he says.
There were a number of questions raised in the data, based on what I gathered from Pi-Sunyer.
About twice as many patients on Contrave dropped out of the study because of adverse events as compared with placebo (25.9 percent on the drug, versus 12 percent on placebo.) There was also considerable amount of individual variability in how some patients responded well, and others didn’t. The adverse events were predictable for a drug that works on the central nervous system—nausea, headache, constipation, and dizziness.
By shedding pounds, researchers expect a number of other positive things happen for patients’ overall health. Waist sizes shrank, cholesterol and triglyceride levels dropped, depression rates came down, and self-esteem went up. Contrave patients didn’t have any increased risk of suicidal thinking, a rare but obviously problematic effect that ultimately stopped a weight loss drug developed by Sanofi-Aventis from making it to the U.S. market a couple years ago.
Orexigen remains optimistic that it will win FDA approval of Contrave, although Pi-Sunyer said he’s not so sure. “I don’t think it’s quite as good as (Vivus’) Qnexa, and it’s almost as good as (Arena’s) lorcaserin, he says.
Ultimately, he’s not sure any of these drugs will tap the market’s demand for obesity medicines. A hit drug in this disease would need to help people shed between 10 percent and 15 percent more of their body weight than a placebo, particularly because consumers will have to pay for these drugs out of their own pockets instead of getting insurance to pay, Pi-Sunyer says. Drugs like this will probably cost $150 a month, which will force many patients to really ask whether it’s worth the expense.
“I’m not sure any of the three drugs will make a dent in the problem,” Pi-Sunyer says. “When people have to pay for this out of their own pocket, they want something truly effective.”
Even so, when I asked him if he’d prescribe the drug to his patients if it were available today on the market, he said yes. “Since some people get a much better effect than others, I’d have them try it for a couple months and then stop if it’s not working” Pi-Sunyer says.
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