Fda approval

LA JOLLA, Calif. - Shares of Orexigen Therapeutics Inc. plunged in after-hours trading Thursday as study data on its obesity drug Contrave fell shy of a Food and Drug Administration benchmark needed for approval. The stock plunged $2, or 33.1 percent, to $4.05 in after-hours trading after closing at $6.05 during the regular trading session. The drug met study goals of reducing body weight and improving cholesterol and other heart measures in a late-stage study. Still, the weight-loss difference between Contrave and placebo patients was only 4.2 percentage points, short of the FDA's standard of at least 5 percentage points. The results could help heat up a potential three-way race between Orexigen; Mountain View, Calif.-based Vivus Inc.; and San Diego-based Arena Pharmaceuticals Inc. Each company has an obesity drug in late-stage development, with goals of asking for Food and Drug Administration approval by the end of 2009. With the potential for three drugs entering the market so close to each other, slight differences in effectiveness could make all the difference for a company. In the current Orexigen study, obese patients taking Contrave lost between 20 and 25 pounds, or between 9.3 percent and 11.5 percent of their body weight, compared with placebo patients losing between 11 and 16 pounds, or between 5.1 percent and 7.3 percent of their body weight. Also 41.5 percent of Contrave patients, or more than double the amount of placebo patients, lost more than 10 percent of their body weight. The weight loss occurred over slightly more than a year. Still, Contrave only reduced 4.2 percentage points more body weight than placebo based on one measure, shy of the FDA's bar. The company said the results should still satisfy the agency. Also, it still has three other late-stage studies on the drug, with results due in mid-2009 and hopes for an FDA application by the end of the year. "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," Chief Medical Officer Eduardo Dunayevich said in a statement. Contrave also met secondary goals of improving HDL, or "good" cholesterol, and improved potential heart risks. The study used full doses of the drug, which is a combination of 32 milligrams of naltrexone SR and 360 mg of bupropion SR. The doses were gradually adjusted for four weeks, then given in full for 52 weeks. The company also said the results showed a good safety profile, with no associated risks of depression or worsening of blood pressure. The most common side effects included nausea, headache, constipation and dizziness, with 4.6 percent of participants dropping out of the study because of nausea. That marks an improvement over a 11.1 percent discontinuation rate seen in earlier studies. The most recent study used a different release formulation of the drug. The Contrave results come one month after potential competitor Vivus said its developing obesity drug Qnexa met a late-stage study goal of reducing weight versus placebo. In that study, patients taking 15 milligrams daily of Qnexa lost an average of 19.8 pounds over 28 weeks, while patients taking 7.5-mg doses lost 18.2 pounds. Full-dose patients lost 9.2 percent of their body weight, compared with 8.5 percent for the half-dose patients and 1.7 percent on average in the placebo group. The most common side effects were a "pins and needles" sensation, dry mouth, altered taste and constipation. A third potential competitor in the field is Arena, which could release late-stage study results on lorcaserin near the end of March. It hopes to apply for FDA approval by the end of 2009.

Three-way race between 

Orexigen Therapeutics Inc (Contrave); 
Mountain View, Calif.-based Vivus Inc.; 
and San Diego-based Arena Pharmaceuticals Inc.