From Monday's New York Times:
nytimes.com
November 17, 1997
Patents: New Drug for Diabetes
By SABRA CHARTRAND
he onset of diabetes rarely leads people to scour medical texts or
the Internet for experimental drugs or alternative treatments.
Millions of Americans are diabetic, and they, along with almost everyone
else, know that the potentially life-threatening condition can be controlled
with insulin injections or a combination of weight loss, exercise and oral
medication.
They may not realize, however, that in healthy people insulin works in
partnership with another hormone, or that since 1921 only the insulin part
of the equation has been available as a drug.
Now a San Diego pharmaceutical company has won a patent for what it
calls the first new diabetes drug since the discovery of insulin. The patent
covers a synthetic version of a natural hormone called amylin, discovered
only 10 years ago, that circulates in the blood alongside insulin.
When people eat, blood sugar, or glucose, rises. To control blood-sugar
levels, the pancreas secretes two hormones, insulin and amylin. However,
if the pancreas is not working properly, the secretion of one or both
hormones is disrupted and blood-sugar levels can run amok, causing
diabetes.
Diabetes is generally classified as either Type 1, in which the body does
not produce insulin, or Type 2, in which the body does produce insulin
but cells do not respond properly to the hormone, leading to an
accumulation of blood sugar.
The conventional remedy for Type 1 diabetes, also known as juvenile
diabetes because it most often strikes people 20 or younger, is regular
injections of insulin.
Type 2 diabetes, which affects 90 percent to 95 percent of people with
the disease, most often strikes adults and can be controlled through
weight loss, exercise and oral medication, although some people still need
to inject insulin.
"The discovery of insulin was one of the great breakthroughs in
medicine," said Ted Greene, chairman and founder of Amylin
Pharmaceuticals Inc. Until 75 years ago, diabetes was considered a
childhood disease because juvenile diabetes was its most prevalent form.
"Diabetes was, at the time, the most feared disease of childhood, like
polio became several years later," Greene said. "You had 12-year-old
children dying all over the place. So the breakthrough discovery of a
hormone in the pancreas that allowed those children to continue living
normal lives was exciting. At the time, the world assumed that the
problem of diabetes had been solved."
Except that even with the long-term use of insulin, diabetes can cause
complications like blindness, kidney failure and heart disease.
"The other thing that happened in midcentury was that as people literally
came off the farm and sat down in front of their TVs, Type 2 diabetes
exploded," Greene said. "It is almost always associated with obesity and
inactivity."
The search for an alternative to injectable insulin led to pills that lower
glucose levels. But they do not work for Type 1 diabetes, and after a
time, their power diminishes in people with Type 2.
Greene estimates that out of 16 million diabetics in the United States,
only half are aware they have the disease. Of those, about 5 million are
adult-onset diabetics and about 2 million are juvenile diabetics.
Even those diabetics who do not mind using a needle know that insulin is
not foolproof. For many diabetics, insulin replacement means constantly
estimating how much insulin to take before eating, so that post-meal
glucose levels will remain in the right range.
"While the world viewed diabetes as pretty well taken care of, the
medical community and juvenile diabetics especially viewed it as a real
problem," Greene said. Then, in 1987, researchers at Oxford University
found a second molecule that circulated in the blood alongside insulin and
acted to control metabolism of carbohydrates, fats and proteins. That
molecule was amylin.
"Insulin increases the outflow of glucose from the blood," Greene said.
"But amylin acts to slow the inflow into the blood. With just insulin, you're
trying to adjust the outflow valve without any control of the inflow."
Since natural insulin and amylin work in tandem to control blood sugar,
scientists hoped that the combination in a drug would make a more
effective treatment for diabetics. But amylin in its natural form is sticky --
it clumps on needles and forms little rocks in the pancreas. Researchers
first had to create a synthetic version that they could work with more
easily and reliably.
The inventors at Amylin Pharmaceuticals -- Laura Gaeta, Howard Jones
and Elisabeth Albrecht -- altered amino acids in the molecule and created
a new drug named Pramlintide.
"We think that the combination of insulin and amylin together will lead to
better metabolic control for patients, lower glucose levels, better control
of body weight, and improvement in the ratio of good to bad
cholesterol," Greene said.
His company now holds 14 patents for technologies related to the
synthetic hormone and its use in treating diabetes.
"We have patented the concept of any molecule which mimics the actions
of this hormone as a treatment of diabetes," Greene said. "We believe
this is unprecedented in the pharmaceutical industry."
Amylin Pharmaceuticals is now conducting clinical trials in which
thousands of patients are taking either the drug or a placebo. The
company hopes to request approval from the Food and Drug
Administration sometime in 2000.
It received patent 5,686,411.
Patents are available by number for $3 from the Patent and Trademark
Office, Washington, D.C. 20231.
Harrison Hickman |
