http://www.cbsnews.com/stories/2005/...in828098.shtml



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Cure Interrupted?
Human Guinea Pigs Bewail Withdrawal Of Experimental Drug!

NEW YORK, Sept. 11, 2005

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(CBS) Say you got an incurable disease and went on medication that you believe was making you better.

Imagine the anguish if the company that made the medication took it away from you.

Well, that’s what has happened to one-time marathoner Bob Suthers, who watched his body degenerate from Parkinson’s disease. His symptoms became so acute he all but lost hope when he agreed to become a human guinea pig in a clinical trial for a new drug, GDNF, made by the biotech company Amgen.

Correspondent Lesley Stahl reports for 60 Minutes.

Suthers and his doctor said GDNF was looking like a breakthrough when Amgen took it away. Suthers says the drug company used him – and then just tossed him aside.

Today, Bob Suthers is a desperate man. He’s been off GDNF for a year now, and says he’s back to where he was before he got the drug, struggling to do the simplest of chores. He says he was like this in 2004 when his doctor told him about a clinical experiment, one that involved an elaborate, expensive and, above all, risky procedure.

Suthers was one of 48 patients to have two metal pumps surgically implanted in his abdomen. Then holes were drilled through his skull and catheters inserted into his brain.

But there were complications. Suthers had a stroke after the surgery, so he had to go back for a second surgery.

"My wife said I was the bravest man she ever — she ever knew," he recalls.

Finally, after months of recovery, he got the drug.

Did he suddenly begin to feel better? Did it gradually improve? What happened?

"It was a gradual thing," says Suthers. "But I knew there was an improvement. I stopped falling down. I could think more clearly. Everything."

Suthers’ daughter, Kristen, says he got to where he was walking two miles at a stretch, when without warning, without consulting any of the doctors working with the patients, Amgen stopped the study and ordered the doctors to remove the pumps.

"What they did," says Suthers, "was unconscionable. They took hope away from us."

Says Stahl, "They pulled the plug on you, what you wanted to say."

"Yes, they did," Suthers responds.

Says daughter Kristen, "They just left these people to die."

Amgen said it was a safety issue: when an animal study showed that some monkeys on large doses of GDNF developed lesions on their brains, outside toxicologists recommended the experiment be stopped at once.

Suthers' reaction: "What’s a safety issue when I’m going to die a slow death? What is a safety issue? I don’t understand that."

Adds daughter Kristen, "One of the doctors at Amgen, on the phone to my mother, said, 'Well, you wouldn’t want your husband to be brain damaged, right, from this drug?' And my mother said, 'My husband’s already brain damaged.'”

But the company said the drug didn’t work. Results showed that after six months, patients in Bob Suthers’ trial showed “no clinical improvement compared to (those taking a) placebo.” Amgen consulted bioethicist Arthur Caplan about canceling the trial, and he told them they were justified on ethical grounds.

"The objective analyst said, 'We’re not seeing that much improvement,'" explains Caplan. "Sure, the subjects are reporting good things to us. That often happens. They have a stake in hope and wanting it to work. We don’t go with hope when it comes to really trying to do the hard science."

Neurologist John Slevin at the University of Kentucky ran an earlier phase-one trial with higher doses of GDNF. He says he was skeptical about what his patients were telling him at first. But then he saw a video. Before they started on the drug, Slevin's patients were videotaped. In one part, Bob Green is asked to walk across the room, but he can't even get up. He is asked to touch his finger between two dots and he says he can't do it.

After a year on GDNF, the video shows Green walking.

Slevin's question: Could a placebo effect be that profound?

"My gut feeling," he says, "I find that hard to believe."

Other patients in Slevin’s trial were on GDNF for up to two years and reported similar results, like Roger Thacker. 60 Minutes visited Thacker on his farm, where he's struggling against the pain he says had subsided when he was on GDNF.

His wife, Linda, says that after 11 months on the drug, Roger was back on his tractor for the first time in two years.

She says, "You cannot fake not having the symptoms of Parkinson’s. It’s painful, it’s disabling, and as much as you would like, and as strong-willed as my husband is – he would fake it if he could -- there’s no way."Bob Green, a minister, is the man in the video that Slevin showed 60 Minutes. He says, "If the placebo effect was a week or two, I would understand that and say, 'Yes, you’re right.' You know. But two years later to be gaining ground and making real progress? That’s far from a placebo."

Phase one patients (a group in Kentucky plus five more in England) took GDNF for up to three years, and according to published reports, all improved dramatically.

So why did the data from the phase two trial fail to show greater benefits? Several of the doctors argue that the patients were on the drug for only six months (not long enough) and were given too low a dose. So convinced the drug was safe and effective, the doctors wanted Amgen to at least provide it under compassionate use.

Stahl asks Caplan, the bioethicist: "Does the company have some kind of an ethical obligation to at least continue compassionate use for the people they’ve put through these experiments?"

Caplan's answer, "Normally, you would say yes to that. The issue in this particular study, though, is they’ve got animals that are getting problems."

But Slevin, in Kentucky, suspects that those monkey lesions could have resulted from abrupt withdrawal from a toxic dose, ten times the concentration the patients got. To demonstrate that his patients were OK, he compared scans of their brains from before they took the drug, to after, and saw no damage. He took his evidence to the Food and Drug Administration (FDA).

"What the FDA told us," says Slevin, "they didn’t see any reason why they shouldn’t be allowed to continue having the drug as long as things were being monitored."

Stahl: "And still Amgen wouldn’t do it?"

Slevin: "No."

"You must have been frustrated."

Slevin: "Yes."

Amgen declined to give 60 Minutes an interview, but sent a statement saying it has an ethical obligation to “protect patients …against the possibility of drug-induced adverse effects.” Bioethicist Caplan says recent lawsuits involving the safety of drugs like Vioxx were a huge factor.

Explains Caplan, "We’ve made a very jittery pharmaceutical industry. And I will tell you, at the first sign of problems in animals, even if you’re giving them a million times the dose that you’re going to give a human being, they start to say, 'That’s it. We’re outta here. This is not something we can pursue.'"

Aware of the company’s fear of liability, the patients have made assurances they will never sue Amgen.

Stahl says to Linda Thacker, "You’re saying that even if your husband suffered – I’m thinking the worst case scenario, brain damage."

Linda Thacker: "Lesions."

Stahl: "Lesions, whatever. No suing, period. That’s the end of it. You accept."

Linda Thacker: "I’ll sign. My husband will sign. His daughter will sign. Right now, it’s the same mindset we had when we went into the study to begin with. We have nothing to lose."

Even if these particular patients promise in a kind of legal contract that they will not hold Amgen the company liable, even if they give away every chance they have to come back and sue.

The problem? "The companies don’t believe them," says Caplan. "We’re in a litigious society to the point where people will say, 'That won’t be worth anything. You can’t waive your rights to sue me.'”

Off the drug and getting worse by the day, Bob Suthers and eight of the 10 Kentucky patients decided to go to court to force Amgen to give them GDNF. Even though they all had signed a consent form acknowledging the company could stop the experiment, they hired attorney Allan Milstein to argue that the decision about continuing the drug should be in the hands of the principal investigators, the patients’ own doctors – not the company.

Attorney Milstein: "The principal investigators said, 'We think Amgen’s wrong. Keep the pumps in there and we’re going to try to get you the drug.'”

Stahl: "Have you ever seen doctors defy a company quite like that before?"

Attorney Milstein: "No."

Stahl: "Or heard of it?"

Attorney Milstein: "Never."

Stahl: "I spoke to somebody who said it would be unheard of, if a court ordered a company to give a drug. I mean, that the court really wouldn’t have the power to do that. And it would set a terrible precedent."

Attorney Milstein: "Well, I don’t think it would set a terrible precedent. This is an unusual case. "

That's because, he says, the patients went through so much. Roger Thacker has his own theory of why Amgen stopped the trial:

Thacker: They know it works. What we’re talking about here is money and delivery system. Our delivery system is not viable anymore.

Stahl: You’re saying the idea of having brain surgery, stomach surgery, that’s not going to work for everybody with Parkinson’s.

Thacker: You can’t afford it.

Stahl: Can’t afford it. So they need to come up with…

Thacker: What they’re gonna come up with, I believe, is an encapsulated form where you get up every morning and…

Stahl: Take the pill and that’s it.

Thacker: You’re done.

Stahl reports that 60 Minutes doesn't know whether Roger Thacker has it right. But they found this statement by Amgen's vice president of research, Roger Perlmutter, on the Internet. It's from a speech from when the phase two trial was still under way:

"There aren’t enough neurosurgeons in the country to actually do that procedure and there aren’t enough neurosurgical suites in which to actually do it. So that would limit you pretty dramatically. This is not a therapy from our perspective that is going to be a huge moneymaker for Amgen. It’s just, you’re never going to get there."

Eight days after Amgen stopped the trial, the company applied for another patent for GDNF, along with new ways to deliver it, including an encapsulated form.

For the patients, their only chance of getting GDNF is their court case, which won't go to trial for several months. Roger Thacker says he risked his life for Amgen with brain and stomach surgery. Now, he says, they owe him.

"Yeah," says Thacker. "My point is, I don’t feel like the guinea pig. I’m not a lab rat. I’m a human being. I signed a contract with them, and they have rights, and I recognize that. But in return, they should be doing the same thing for me."

Says Suthers, "It’s like being a racehorse. And when he’s no further use to them, they take him out and shoot him. And that’s just what it’s like."



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