The source of this article is the New York Times: http://tinyurl.com/3zgx8

February 12, 2005
Patients in Test Won't Get Drug, Amgen Decides
By ANDREW POLLACK

  small group of people with Parkinson's disease had been pleading for months
with the biotechnology company Amgen: Let them resume taking an experimental
drug that the patients said had helped them but which the company said was
ineffective and possibly dangerous.

Yesterday Amgen gave its answer: no. The company said it would not make the
drug available to the four dozen patients who had participated in its
clinical trials, even though the Food and Drug Administration had left the
door open for it to do so.

Company executives said that besides exposing the patients to unnecessary
risks, to let them continue treatment would only generate false hopes. It
might also ultimately hinder development of improved versions of the drug,
Amgen said.

"I know this will be received by the patients in a devastating way," Kevin
W. Sharer, chief executive of Amgen, said in an interview, describing the
verdict as "the hardest decision I've made in my life." But, he added,
"we're trying to do the right thing for the most people."

Some patients, along with their family members and doctors, reacted swiftly
and angrily, as did some patient advocacy groups.

"They have every reason in the world to give this medication to the
patients, and they're not," said Kristen Suthers, whose father had received
the drug and who has been one of the main organizers of the patient protest.
"To be able to decide whether people are going to suffer - I just wish that
I'd never heard of the company."

She said the condition of her father, Robert Suthers of Huntington, N.Y.,
had improved to the extent that he could walk two miles while on the drug,
but now can no longer even bathe himself.

The controversy over the drug raises the question of whether drug companies
are obligated to continue providing drugs to participants in clinical
trials, even after the trials are ended. In this case, to receive the drug
the patients had to undergo surgery to have catheters implanted in their
brains and pumps in their abdomens.

"We think there is kind of a moral pact that one makes with a company in
these situations that gives the patients a privilege of having continued
access to treatment," said Robin Anthony Elliott, executive director of the
Parkinson's Disease Foundation.

But Dorothy E. Vawter, associate director of the Minnesota Center for Health
Care Ethics, said the question was "not a settled area of research ethics at
all and is raising its head more and more all the time." She said an
obligation to provide drugs to patients indefinitely after trials end could
discourage drug development.

Amgen's decision reverberated beyond the patients in the trials because the
drug, called glial cell line-derived neurotrophic factor, or GDNF, had the
potential to stall or even reverse the progression of the disease rather
than just reduce the symptoms, as the currently available Parkinson's drugs
do.

"As someone with Parkinson's disease who for four years has had GDNF as my
big hope, it's absolutely devastating," Tom Isaacs, co-founder of the Cure
Parkinson's Trust in England, said of Amgen's decision. Mr. Isaacs walked
around the coast of Britain, more than 4,000 miles, to raise money for
Parkinson's research, planning, he said, to devote much of that to studies
of GDNF.

In initial trials in England and Kentucky involving a total of 15 patients
who knew they were getting the drug, virtually all experienced reduction of
the tremors and rigidity that characterize the disease, and in some cases
the improvements were substantial. But a subsequent trial involving 34
people who did not know whether they were getting the drug or a placebo,
indicated that the drug did not prove meaningfully better than the placebo.

Amgen concluded that the positive results in the earlier trials represented
a placebo effect, something that is known to occur in Parkinson's trials.
Moreover, it said, it found that some monkeys given high doses of the drug
had developed potentially serious brain damage. So last summer the company
stopped the trials and ordered all patients taken off the drug.

Some doctors involved in the trial, however, have argued that the
unsuccessful trial was poorly designed and that the drug worked. They also
discounted the findings in monkeys, saying the animals had received a much
higher dose than the patients.

Amgen executives and some of the investigators met with the F.D.A. in
January. According to the company, the agency said that safety issues would
preclude the drug from being given to new patients but that it would
consider allowing Amgen to resume treating the existing patients.

Amgen executives said they held many meetings among themselves and talked
with outside experts and ethicists. In the end, the executives said, they
decided they had to stick with the scientific evidence that the drug might
be dangerous and had not been proved effective.

Mr. Sharer said another factor was that if the drug supply were resumed and
some patients experienced a placebo effect they attributed to the drug,
pressure would only grow on the company to start treating even more
patients. "We couldn't find a way to contain this medicine to just these 40
or 50 patents," he said.

He said the company was committed to GDNF and hoped to begin another trial,
perhaps delivering the drug by another method, a year or two from now, if
the safety issues can be resolved.

"The best thing to do for all patients is to do a proper development of
GDNF," Mr. Sharer said. He said that money was not a factor in the decision
and that concerns about the company's legal liability had not been an
insurmountable barrier.

Amgen executives also said that there was already an approved therapy, deep
brain stimulation, that could help alleviate the symptoms of the patients
from the clinical trials.

An ethicist consulted by Amgen, Arthur Caplan of the University of
Pennsylvania, said he agreed with the company. Patients "are not in a
position, even though they are the recipients, to really understand what is
going on in terms of animal signals that may harm them," Mr. Caplan said
"And what they interpret as positive might be colored by hope."

A similar stance was taken by John G. Nutt, a professor of neurology at
Oregon Health and Science University who treated four patients in the trial;
none of them benefited. He said that four of the patients in the trial who
were among those showing the greatest benefits had turned out to be taking
the placebo. "Should those patients be offered placebo?"

In contrast, doctors at the University of Kentucky who conducted one of the
early trials, criticized Amgen's decision. So did one of the patients
treated in that trial.

The patient, Bob Green, 51, of Wilmore, Ky., said GDNF had allowed him to
dress himself, get out of bed by himself and even drive on occasion. "So
many things that people consider trivial are major to those of us who lack
those abilities," he said. Now off the drug, he said his condition was
deteriorating.

"I think it's a sad commentary on Amgen's outlook on life, especially as it
pertains to us who readily put ourselves on the line to test the
medication," he said. "We went through the surgery thinking it might offer
hope for us and for others."

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