December 30, 1998
NEW YORK (AP) _ The pain started as a cramp in Joe Oliva's toes and
ankles. Within six months, he could no longer walk. The slightest
pressure on his feet caused severe pain. He had to quit his job as a
limousine driver.
"If I tried to sleep with a blanket, it felt like a lit cigarette on my
toes," said Oliva, 36, of Deer Park, N.Y.
His ailment: Diabetic neuropathy, a nerve disorder that is one of the
most common and troublesome complications of diabetes. Now, three major
pharmaceutical companies are finalizing development of the first drugs
to halt its progression.
Between one-third and one-half of the 16 million Americans with diabetes
suffer from neuropathy. Millions of these patients are undiagnosed.
There's no cure. Neuropathy often causes prolonged numbness in the feet
and hands, which gradually worsens, sometimes leading to foot ulcers,
gangrene and amputation.
The three companies out front on neuropathy are Genentech, Pfizer and
Warner Lambert. They are in final stages of human testing for drugs to
stop diabetic neuropathy from moving to its most severe stages. They may
reverse damage already done.
The increase in diabetes research among large drug companies parallels a
slow rise in public awareness of the sixth leading cause of death.
Like others, these three companies are attracted to the economics of
treating diabetes.
With the aging population and increasing awareness, the number of
diabetics seeking help is expected to steadily rise. Like other drugs
for chronic diseases, patients would likely have to take a neuropathy
medication for life.
In addition to diabetes, neuropathy is also caused by rheumatoid
arthritis, cancer, leukemia, kidney disease, shingles and can be induced
by certain drugs. As a result, the market for a neuropathy drug could be
huge.
Even if only 10 percent of people with diabetic neuropathy took the
drug, analysts say a company could reach $1 billion in annual sales.
"If they are successful, it has blockbuster potential," said Charles
Engelberg, an analyst with AmeriCal Securities.
Pfizer and Warner Lambert have other diabetes drugs in development or on
the market. Pfizer is working on an inhaled form of insulin, replacing
injections. Warner Lambert last year introduced Rezulin, a pill which is
now one of the biggest selling diabetes drugs.
The neuropathy drugs offer hope for treating one of the more vexing
complications of the disease, said Dr. Gerald Bernstein, director of the
diabetes management program at Beth Israel Health System in New York and
president of the American Diabetes Association.
"If we can regrow nerves that will make an extraordinary difference,"
Bernstein said.
Neuropathy involves the steady degeneration of the wiring around nerves
that are essential for the brain to communicate with muscles, skin and
organs.
In diabetics, the lack of insulin leads to production of an enzyme
called aldose reductase, which creates a sugar that does the damage.
Up until now, doctors gave patients narcotics to mask the pain and
anti-depression medications. Or they told patients to learn to live with
it.
Previous research attempts failed because the drugs wouldn't absorb into
tissues, or caused liver problems.
"It's been a tortuous process," said Tom Beyer, a research executive at
Pfizer. "The body does not like drugs that get into the nervous system
and there are barriers that are very difficult to cross," Beyer said.
Pfizer's drug, Alond, and Warner-Lambert's Zenarestat, are pills and
attack neuropathy by inhibiting aldose reductase production. American
Home Products has a similar drug in an earlier stage of development.
Genentech's drug, Neuleze, is considered farthest along and company
officials are hoping positive test results in 1999 will lead them to
quickly seek Food and Drug Administration approval.
Neuleze, which is given by injection, uses a genetically engineered
hormone that attempts to stimulate nerve growth.
Published studies show 75 percent of the 250 patients receiving three
injections a week for six months reported fewer symptoms, compared to 49
percent of patients given a dummy drug. The only significant side effect
is tenderness at the injection site.
Oliva was among those participating in tests of the drug. He said it
restored reflexes in his ankles, which helped him walk again.
"I could function as a human being and not have to worry about pain from
shoes or socks," he said.
Ultimately, researchers say a combination of drugs, including
painkillers, will likely be used to treat neuropathy.
Copyright 1998 The Associated Press. All rights reserved.