Neurogen designs drug that shows promise for 1st weight-loss pill
Abram Katz
Branford biotechnology company Neurogen has successfully completed the first in a succession of tests that could ultimately yield a clinically useful weight-loss pill.
The proprietary molecule, called NGD-4715 was tested in 71 people and found to be well-tolerated and non-toxic, according to Neurogen president and chief executive officer William H. Koster.
Koster said NGD-4715 is the first drug of its type to gain a foothold in the federal regulatory process.
NGD-4715 is a small molecule that interferes with the brain's system for controlling appetite.
Other substances, such as leptin and neuropeptide y, have also curbed cravings for food in animals, but were disappointing in human tests or never reached that stage.
Koster said NGD-4715 apparently regulates those and a complex chain of other substances that regulates food intake.
The potential drug has been shown to reduce appetite and weight in laboratory animals, but ensuring that it is safe for people is a long, arduous process.
Additional tests will be conducted in the end of the year to judge the safety and workings of the drug, Koster said.
Neurogen also expects to study the efficacy of the compound by the end of the year. If all goes well, the drug would then be subject to a large-scale test, the last step before federal approval.
NGD-4715 targets a melanin concentrating hormone receptor (MCHR1) in the brain. The hormone was discovered in the late 1990s to regulate coloration in fish.
"In mammals, it appears to regulate caloric intake," Koster said.
In previous research, bioengineered mice with the receptor knocked out became extremely lean, while other mice designed to over produce the hormone became obese, he said.
MCH receptors are concentrated in a structure in the brain called the hypothalamus, which regulates body temperature, blood pressure, weight and many other functions.
While mice have only one type of melanin concentrating hormone receptor, dogs and humans have two. The neurogen molecule was designed to block only MCHR1. That appears sufficient to dull appetite, Koster said.
"In November 2004, Neurogen showed that blocking MCHR1 in dogs reduced their food intake," he said.
After blocking the MCHR1, about 10 days elapse before statistically significant weight loss starts, Koster said. Animals on NGD-4715 consume 10 to 20 percent less food.
This is good, Koster said, because severe, rapid and uncontrollable weight loss is undesirable.
Koster said Neurogen also conducted experiments to rule out the possibility that environmental factors, rather than NGD-4715, were responsible for the canine weight loss.
The U.S. Food and Drug Administration requires drugs to prove themselves in three types of studies before they are considered for approval.
In the phase one study, which Neurogen just completed, a single, ascending dose is given to see if the drug is safe. A multiple dose ascending study will also be performed as part of phase one, Koster said.
Phase two is generally designed to show whether the drug in question is effective. Finally, phase three is a large study of the drug to check for side effects and other unexpected results.
So far, appetite suppressing drug candidates produced by other companies have also altered ion channels in the heart, which increases the risk of irregular heart beats.
NGD-4715 has already been tested to make sure it has no effect on heart muscle, Koster said.
Currently about two-thirds of adults in the United States are considered overweight.
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