Leptin was hailed as a magic bullet for obesity based on rat studies in the 1990s, and then it failed miserably when Amgen took it into clinical trials. Now Amylin Pharmaceuticals thinks it has found a way to bring leptin back to life as a weight-loss drug, as part of a new combination with Symlin, a drug it markets for diabetes.
San Diego-based Amylin (NASDAQ: AMLN) is presenting data on its new combination weight-loss drug this weekend at The Obesity Society’s annual meeting in Phoenix, AZ. I got an overview of what Amylin will present there about its experimental treatment during an interview with Christian Weyer, the company’s vice president of corporate development for diabetes and obesity.
The opportunity, and risk, here is huge. About two-thirds of American adults are overweight or obese, according to the Centers for Disease Control and Prevention. The pharmaceutical industry has a history of failures here, and the most-prescribed treatment is still an appetite suppressant from the 1950s that causes side effects like nervousness and sleep problems, Weyer said. Since any new obesity drug will be taken by millions on a chronic basis, its safety has be squeaky clean. Madison, NJ-based Wyeth learned the hard way what happens when it’s not. The drugmaker has shelled out more than $21 billion in legal settlements after its fen-phen obesity drug combination was found to damage heart valves in some patients in the 1990s, according to its most recent quarterly report. And France-based Sanofi-Aventis had its Acomplia medicine rejected by FDA advisers last year after reports of suicidal thinking were linked to the drug.
“Safety is absolutely paramount in obesity drug development,” Weyer says.
The ideal profile that Amylin has in mind is a medicine that can help patients lose 10 percent or more of their body weight, keep it off, and do it without any serious side effects like suicidal thoughts, cognitive impairment, or depression, Weyer says.
Amylin’s game plan is unlike other companies, which tend to develop small-molecule drugs, taken as oral pills, that hit receptors on brain cells that control whether people feel full. The problem with those medicines is that they tend to hit other cells in the brain that control moods, leading to side effects, Weyer says.
The Amylin approach is to use pramlintide, a genetically modified version of a hormone that’s secreted from the pancreas to slow down stomach emptying. It’s combined with metreleptin, a genetically modified version of the leptin hormone that’s secreted from fat cells, which sends a signal to the brain that it’s time to stop eating, Weyer says. The company’s scientists believe the drugs have complementary action, which is greater than the sum of either individual part, Weyer says. Since they are relatively large molecules, they are too big to cross the blood-brain barrier, and shouldn’t cause mood-altering side effects, he adds.
Results from a company-sponsored clinical trial in November 2007 seem to back up this hypothesis. It showed that pramlintide on its own helped patients lose 8.4 percent of their body weight after almost six months, which Weyer says “is probably sufficient to get the drug approved, but we’re aiming for greater weight loss.” When given in combination with metreleptin, though, patients lost 12.7 percent of their body weight, or about 25 pounds from the beginning of the study, compared with 17 pounds for those on pramlintide alone. The side effects included injection site reactions and nausea, which were mild to moderate in severity, and didn’t last long, researchers said.
Since these are genetically engineered protein drugs, they need to be given via injection just under the skin twice daily, Weyer says. This sounds like a drawback to me since most patients would prefer an oral pill, but Weyer brushed off the question. … Next Page »
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