Updated: Jan. 8, 2:40 pm Pacific–see below: San Diego-based Orexigen Therapeutics said today that a final-stage clinical trial of its experimental obesity drug reached its main goal of helping patients lose weight. The problem is that meeting the goal may not be good enough.
The study, the first of four trials examining the effects of a long-lasting combination of naltrexone and bupropion, showed that patients lost an average of 20.3 pounds (9.3 percent of their weight) when they took the drug and followed an intense diet and behavior modification program. That compares to 11 pounds (5.1 percent) of weight loss for patients who stuck to the diet and behavior regimen, but got a placebo. The medicine, which Orexigen hopes to market as Contrave, was well-tolerated and wasn’t associated with a higher risk of depression, suicidal thoughts, or high blood pressure, the company said.
The findings look promising at first blush because they met the primary goal of the study, but investors weren’t convinced this is good enough. That’s because the difference between the drug and placebo groups was a loss of 4.2 percent of body weight, which doesn’t meet the 5 percent threshold mandated by the FDA for obesity drugs, according to a report by TheStreet.com’s Adam Feuerstein. Shares of Orexigen (NASDAQ: [[ticker:OREX]]) dropped 36 percent in after-hours trading to $3.87.
Orexigen’s comments about the data were positive, but not ebullient. “The results of this trial indicate that additional, clinically significant weight loss can be achieved when Contrave is added to a rigorous program of diet and exercise,” said Eduardo Dunayevich, Orexigen’s chief medical officer, in a statement. “We are also very pleased with the safety profile demonstrated by Contrave thus far. We look forward to the results from the remaining Phase 3 trials which will further examine the efficacy, safety and tolerability of Contrave with less intensive behavior modification as well as in patients with Type 2 diabetes patients.”
Patient enrollment has been completed in the other Phase 3 trials. The company said it plans to release basic conclusions from the study by the middle of this year, and if they confirm the benefits, Orexigen will file an application with the FDA to market the drug before the end of the year.
Orexigen didn’t say in its statement whether it plans to submit the data for a more complete presentation at a medical meeting or in a journal, but the findings will surely be of interest to a large number of physicians. An estimated 70 million people in the U.S. are considered obese, according to the Centers for Disease Control and Prevention, so any drug that’s effective and safe enough to be given chronically to millions of people without a life-threatening condition could obviously be a big seller.
Orexigen did offer some specifics in its statement, and said it plans to offer more in a conference call with analysts today at 5 pm Eastern time. The study enrolled 793 obese patients at nine U.S. medical centers, who were followed about a year. They generally had a body-mass index rating of 30 to 45. A rating of 18.5 to 24.9 is considered normal, according to the CDC, meaning a normal adult who is 5 foot 9 inches tall would have a weight of 125 to 168 pounds.
Besides helping patients lose weight, researchers said the Orexigen drug offered improvements for patients on their HDL cholesterol, triglycerides scores, and helped them slim down around the waist. Patients on the medicine also showed improvement on quality of life measurements, including one that examined food cravings.
Still, the drug isn’t for everybody. More than one in four patients on the medicine (25.9 percent) dropped out of the study because of side effects, compared with 13 percent for those in the placebo group. Most patients who dropped out complained of nausea, hives, and anxiety. Orexigen said fewer patients in this trial dropped out because of nausea than in a previous study.
Update from the company’s conference call: Orexigen says that the FDA’s guidance to drug developers says there are essentially two ways an obesity drug can be considered effective. One is for a drug to show a 5 percent greater weight loss after a year than a placebo, which the Orexigen drug failed to demonstrate. The other option is to show that at least 35 percent of patients on the drug achieve a 5 percent weight loss, and that twice as many patients do that well on the drug compared to those on a placebo.
The Orexigen drug failed by that second test as well, because 56 percent on the drug had at least a 5 percent weight loss, while 43 percent did that well on placebo. However, when researchers raised the bar to see how many patients lost 10 percent of their weight, then the Orexigen drug looked twice as good, with 42 percent achieving that level, and 20 percent losing that much weight in the control group. Whether that’s a strong enough argument to take to the FDA later this year will depend on how the other trials turn out, and as Dunayevich said, those are hard to predict.
