Diet drug on FDA fast track
While testing a drug for Lou Gehrig’s disease in the mid-1990s, scientists noticed that people receiving the drug were losing weight. It was an unexpected and unwanted side effect.
They eventually concluded that the medication wasn’t helpful for people with the degenerative motor neuron disease, but they didn’t forget their finding.
Today, the drug, Axokine, is poised to become the next prescription weight-loss medication. In January, the Food and Drug Administration gave it “fast track” status because, by facilitating weight loss, it could reduce the risk for heart attack, stroke and diabetes in obese people. The designation means the agency will expedite the drug’s review.
Studies on Axokine indicate that most people taking the drug experience weight loss for a few months. Over a longer period of time, only about one-third of people taking the drug continue to experience weight loss, but for them, the loss can be dramatic.
Although Axokine is still under investigation and is probably a few years from the marketplace, it would offer a new approach to treating obesity. Axokine is a modified form of a naturally occurring protein, called ciliary neurotrophic factor, that acts in the brain to inhibit hunger signals. Initially, scientists believed that patients with Lou Gehrig’s disease might be helped because ciliary neurotrophic factor promotes the survival of nerve cells.
“The hypothalamus, the master gland of the brain, is the Grand Central Station where information on energy intake, expenditure and reserves all converge,” said Dr. Leonard S. Schleifer, president and chief executive of Regeneron Pharmaceuticals, which developed the drug. “Our protein acts by telling the brain that it has enough food and to eat less.”
Axokine also seems to prevent the overeating that occurs when the brain responds to a restricted food intake -- the well-known rebound effect many dieters experience, said Schleifer.
Two-thirds of people who take the drug, however, become resistant to it. Regeneron has a blood test that, Schleifer said, can show who will continue to benefit from taking the drug.
“Overall, everyone appears to benefit for a few months,” he said. “But thereafter, some people continue to benefit and others don’t. In two-thirds of people, their immune system seems to reject this treatment.”
A small study published earlier this month in the Journal of the American Medical Assn. showed that most Axokine users experienced continuous weight loss during 12 weeks of use. A preliminary report on a larger study -- more than 1,400 people taking the drug for one year -- found that among the 30% of people who did not develop resistance to the drug, half lost 5% of their body weight and one-quarter lost 10% of their body weight. This result is similar to the effects of prescription obesity drugs already on the market.
Finally, a 12-week study on overweight and obese people with diabetes, reported last week, found that patients receiving Axokine and dietary counseling lost 6 1/2 pounds compared to 2 1/2 pounds among people receiving only dietary counseling.
Eventually, the drug will be tested in about 4,000 people, according to a Regeneron spokeswoman.
The medication, which patients give themselves in an injection under the skin, appears safe in the studies completed thus far. The company is working on a pill version of Axokine.
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Prescription drugs used for weight loss
Three prescription obesity drugs are currently on the market.
The Food and Drug Administration recommends that they be used as part of a weight-loss program that includes diet and exercise.
* Orlistat: Approved in 1999 under the brand name Xenical, the drug blocks intestinal absorption of fat. The major side effects are cramping and diarrhea.
* Phentermine: The appetite suppressant is approved only for short-term use. It was part of the two-drug “Phen-Fen” weight-loss treatment that was halted in 1997 when the other drug, fenfluramine, was linked to heart valve problems and removed from the market. Phentermine is still approved but should not be used by people with heart disease, high blood pressure or an overactive thyroid gland.
* Sibutramine: Approved in 1997 under the brand name Meridia, it increases chemicals in the brain that suppress appetite. The major side effects are possible increases in blood pressure and heart rate.
