New Weight-Loss Drugs Pass First Tests
More Pounds Lost With Epilepsy Drug Zonegran, New Satiety Drug Axokine
April 8, 2003 -- Two new weight-loss drugs may help obese
people, clinical trials suggest.
The findings come in two separate reports. In the first study,
obese people lost 13 pounds after 16 weeks of adding the epilepsy drug Zonegran
to a low-calorie diet. In the second study, the optimal dose of the
experimental drug Axokine helped obese people lose nine pounds in 12 weeks.
Both studies appear in the April 9 issue of TheJournal of the
American Medical Association.
Zonegran is already FDA approved. It's used to treat epilepsy.
During clinical trials, epilepsy patients treated with the drug lost weight.
That was bad for them -- but it might be a good weight-loss drug.
Duke University researchers led by Kishore M. Gadde, MD, put 60
obese volunteers on a low-calorie diet. Half also got Zonegran; the others got
a look-alike placebo. After 16 weeks, those who got only the diet lost about
two pounds. But those getting Zonegran lost an average of 13 pounds. Side
effects -- mostly fatigue -- were mild. However, Zonegran is known to cause
dizziness, impaired thinking, and sleepiness in epilepsy patients. It's also
been linked -- rarely -- to kidney stones. Zonegran's manufacturer, Elan
Biopharmaceuticals, provided the drug for the study.
"The results of this short-term study provide preliminary
evidence that [Zonegran], in conjunction with diet, can be more effective than
diet alone for obese patients seeking to lose weight," Gadde and colleagues
Axokine is a brand new drug with hopes of being a totally
different kind of weight-loss drug. It's a man-made chemical that mimics a
chemical the brain makes to protect itself from injury. It was designed as a
possible treatment for Lou Gehrig's disease. But when researchers gave the
experimental drug to patients, they lost weight.
Later experiments showed why. The drug affects a powerful brain
system called the leptin pathway. Leptin is a chemical messenger that tells you
when you've had enough to eat. Obese people have leptin resistance; they lose
the ability to know when they're full. Axokine apparently bypasses this
resistance and flips the fullness switch.
Mark P. Ettinger of Regeneron Pharmaceuticals Inc. in
Tarrytown, N.Y., and colleagues performed the first study of Axokine's role as
a weight-loss drug in obese people. They put 173 of these volunteers on a
low-calorie diet. Some got fake placebo injections. Others got various
injection doses of Axokine. The study was funded by Axokine's manufacturer,
Regeneron Pharmaceuticals Inc.
After 12 weeks, those on the diet alone gained about a fifth of
a pound. Those getting what turned out to be the best dose of Axokine lost an
average of nine pounds.
Perhaps the best news came in the yearlong period after
treatment. There was no immediate weight gain when drug treatment stopped.
After about a year, patients treated with Axokine started to gain some
There was a high rate of side effects reported for both the
weight-loss drug Axokine and placebo. Side effects that appeared linked to
Axokine treatment included skin reactions at the site of injection, nausea, and
increased cough. These last two side effects weren't as much a problem in those
who got the best dose of Axokine.
A large, ongoing phase III clinical trial is now delving
further into Axokine's role as a safe, weight-loss drug in obese people.