The FDA issued a response letter that asks Orexigen Therapeutics, the maker of Contrave, to check for heart attack or other cardiovascular risks by conducting a "randomized, double-blind, placebo-controlled trial." Randomized, double-blind, placebo-controlled trial randomly assign patients to receive either a drug or a placebo (dummy pill).
In order for Contrave to receive FDA approval, the study must demonstrate that Contrave's heart risks do not exceed the Contrave's benefits. The trial could take years, according to experts.
"We are surprised and extremely disappointed with the Agency's request in light of the extensive discussion and resulting vote on this topic at the December 7 Advisory Committee meeting," President and CEO of Orexigen Michael Narachi says in a news release. At that meeting, an FDA advisory committee voted 13 to 7 to recommend approval of Contrave despite its modest effectiveness in helping people lose weight.
Contrave (naltrexone SR/bupropion SR) is an investigational medication for the treatment of obesity.
Contrave combines two well-established drugs, naltrexone and bupropion, in a sustained release formulation (SR) into one that experts hope will control eating and help people lose weight safely.
The two drugs are naltrexone, used to treat alcohol and cocaine addiction, and bupropion (known mainly as Wellbutrin), an antidepressant, which also helps people quit smoking.
Together, the drugs affect both appetite or satiety and motivation, or the drive to eat.
Naltrexone impacts the brain's opioid receptors, which are involved in feelings of pleasure and reward. Bupropion increases brain levels of dopamine, the notorious "feel good" chemical that is also released when cocaine or amphetamines are taken.
"It gives you a little kick so you feel okay and don't have to look for food," says Gene-Jack Wang, MD, a senior scientist with Brookhaven National Laboratory in Upton, New York. " Contrave is very similar to amphetamines, but it's not so effective, [which is] better because if it's too effective, it makes you more addicted."
Contrave’s Risks May Outweigh Its Benefits
In previous studies, people taking Contrave lost only 4.2% more of their body weight compared to those taking a placebo. This is below the FDA standard of 5%. It may be Contrave’s “kick” that may be the cause of FDA’s concern.
Series of FDA Rejections of Weight Loss Drugs
Contrave is the third weight loss drug in recent months to be rejected. The FDA formally rejected locaserin from Arena Pharmaceuticals and Qnexa from Vivus in October 2010.
The agency has become very focused on the safety of diet drugs because of their potential widespread use by not only obese patients but by people looking to lose a small amount of weight. Nearly two-thirds of American adults are overweight or obese.
Contrave is an experimental drug that combines naltrexone, an opioid blocker used to treat addictions, and bupropion, an antidepressant, to suppress food cravings for the treatment of obesity, according to its maker.
News release, Orexigen Therapeutics Inc.
FDA News Release