Obesity patients treated with a weight-loss combination pill from Orexigen Therapeutics ( OREX) lost an average of more than 13 pounds, or just more than 6% of their body weight, after one year of treatment, according to results from two phase III studies released Monday. In a third study also released Monday, obese patients who suffered from Type 2 diabetes were able to reduce blood sugar levels but lost less weight. Orexigen said three studies of the weight-loss drug known as Contrave, which combines two older medicines into a single pill, met their pre-specified weight loss and safety goals. The company plans to seek regulatory approval for Contrave in the first half of 2010 from the U.S. Food and Drug Administration. Patients treated with a placebo pill for one year lost about three pounds, or just more than 1% of their body weight in the first two studies. This puts the placebo-adjusted percentage of weight lost by Contrave patients at 5% -- matching one of two efficacy standards mandated by the FDA for all experimental obesity drugs. Overall, three times as many Contrave patients were able to shed pounds compared with patients treated with a placebo for one year. In the first two studies, 48% and 56% of Contrave patients, respectively, lost at least 5% of their body weight. By comparison, 16% and 17% of placebo patients lost 5% body weight. The FDA requires that any new obesity drug at least double the percentage of patients who lose 5% of their body weight compared with placebo, so Contrave easily surpassed this standard.
In the diabetes study, the placebo-adjusted weight loss demonstrated by Contrave was less robust at 3.2%, but more than twice as many Contrave patients lost 5% of their body weight compared with placebo patients. The drug also helped these patients lower their blood sugar levels by one-half of a percent, which is considered clinically meaningful. Contrave consists of two currently approved drugs combined together to suppress appetite and fight food cravings. One of the drugs in Contrave is naltrexone, currently used to fight opioid and alcohol addiction; the other drug is the antidepressant bupropion. Several dose strengths of Contrave were tested in the phase III studies, with the middle dosage, which uses 360 mg of bupropion and 32 mg of naltrexone, the most effective. The company said it would seek approval for this dose and for a lower dose using 16 mg of naltrexone. Nausea is a common and well-known side effect of naltrexone and was the major cause of discontinuation in previous Contrave studies. Orexigen did not disclose the drop-out rate because of nausea from the three studies announced Monday, but the company did say that nausea was the most common adverse event -- mild to moderate, transient and manageable. In the first two studies, 60% and 55% of patients, respectively, completed one year of treatment. Overall, there were seven serious adverse events attributed to Contrave, including two patients who suffered seizures, which is a known side effect of bupropion. No meaningful treatment effects related to heart or liver damage were reported, and there were no reports of an increase in depression or thoughts of suicide among Contrave patients.
Losing 5% body weight may not seem like a lot, but for obese patients, even that small percentage shrinkage translates into health benefits, said Dr. Ken Fujioka, director of nutrition and metabolic research at Scripps Clinic in San Diego and an investigator in the Contrave studies. "Five percent weight loss is enough to change medical issues for these patients. It can keep them from becoming diabetic, or if they are diabetic, it can help lower blood sugar," he said. When drugs like Contrave are added to strict diet and exercise regimens, weight loss can be even more substantial, Fujioka added. Orexigen is one of three relatively small drugmakers -- Vivus ( VVUS) and Arena Pharmaceuticals ( ARNA) are the other two -- in a race to develop the next generation of obesity drugs. In March, Arena reported phase III results which showed that its drug, lorcaserin, led to a 3.6% placebo-adjusted weight loss, although more than twice the number of lorcaserin patients lost 5% of their body weight compared with placebo. Results from phase III studies of Vivus' drug are expected later this year. Orexigen shares closed Friday at $5.69.