Take Two of These, and Go to the Gym

A new class of drugs could significantly increase the benefits of an overall weight-loss regime. But first, drugmakers have to prove they're safe

by Arlene Weintraub

It's a crisp morning in early February, and Barbara Aukland has arrived at the Scripps Clinic's Center for Weight Management to get a checkup. She has been participating in a clinical trial for a new weight-loss drug, Contrave, for the past year. The drug was developed by Orexigen Therapeutics (OREX), one of 20-odd companies racing to develop new obesity treatments. Orexigen, it turns out, is based across the street, in a small office park in this neighborhood of northern San Diego.

Contrave is part of the next generation of obesity treatments now making its way through the pharmaceutical industry's pipeline. About a half-dozen of these new drugs are in critical phase III clinical trials—the final stage of human testing that's required for product approval from the Food & Drug Administration. The market is wide open: Of the $33 billion a year Americans spend on weight-loss products, only $200 million goes to prescription drugs. That's because most of the drug options out there only help people lose 5% to 8% of their weight, and they can cause side effects like jumpiness, insomnia, and upset stomach. Contrave is a combination of an antiaddiction medication and an antidepressant, which together seem to reprogram the way the brain thinks about food. Tiny Orexigen, which is five years old and has yet to get any product on the market, will spend the next two years trying to prove Contrave works safely.

Trial Regimen

Aukland's foray into obesity research began in late 2006, when she saw a news report about Orexigen's trials. At the time, Aukland was carrying 270 pounds on her six-foot frame. As the manager of a cat shelter, part-time student, and single mom, she struggled to find the energy to get through the day. "I had chronic hip and foot pain," says Aukland, 40. "I'd lie in bed and cry." Volunteering for the study wasn't an easy decision: She knew there was a 50/50 chance she would be taking a placebo. Plus as part of the study, she would have to exercise and participate in a support group. Still, she signed up.

Orexigen's trial is unusual in its complexity. Like most weight-loss studies, it is double-blind, placebo-controlled, meaning the company, doctors, and patients won't know who was actually on the drug until the trial ends. But some parts of the trial, including the one Aukland is participating in, also include intensive behavioral-modification programs. Patients are put on strict diets, and given round-the-clock access to dieticians who act as coaches. They meet with other patients in groups, creating Alcoholics Anonymous-type interactions meant to encourage patients to stick with the program. And they are hounded about exercising until they finally break down and do it. For Aukland, that was the hardest part. "They told me to try a stationary bike for 10 minutes, three times a week," she recalls. Once she realized it wasn't aggravating her painful joints, she kept riding, and today works out six days a week for at least 45 minutes. "I started loving it."

Additive Effects of Behavior Modification

The behavior modification part of the studies isn't likely to make the difference between an FDA approval and a rejection for Contrave. But it could very well determine how the label reads if it's approved, and that could make a competitive difference in the marketplace. In early trials, Contrave appeared to produce around 10% weight loss on its own. If diet and exercise add another 5% to that, Orexigen may be able to claim significant double-digit weight loss for an overall program including the drug, plus diet and exercise. "On one hand, it's important for us to know the effects of drug when used in isolation," says Dr. Gary Tollefson, chief executive officer of Orexigen. "But from a real-world perspective, you also want to know the additive benefits of these nonpharmaceutical interventions."