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Amgen finds it's a new world after Vioxx deaths and verdict

Deborah Crowe
AMGEN Inc. once had high hopes for a promising Parkinson's disease treatment called GDNF that it had been nursing since the mid-1990s--even featuring inspiring clips of clinical trial participants in a promotional video shown to investors early last year.

Then, suddenly, everything changed.

The Thousand Oaks biotech giant announced last fall that it would halt clinical trials and stop providing the drug to 48 trial participants, citing its ineffectiveness and evidence of potentially debilitating human side effects.

Not all trial participants agreed. Saying they were benefiting from the drug, they sued Amgen in New York and Kentucky in an unsuccessful effort to force the company to continue providing it to them.

The company said that ethical and patient safety considerations dictated its decision, but other factors might also have been at play--specifically newly heightened fear of litigation amid the lawsuits over Vioxx and other pain medication.

"We don't know what was going on in the heads of Amgen's leadership, but it's hard to escape the suspicion that drug companies these days have a fear of running into a Vioxx situation down the road," said Robin Elliott, executive director of the New York-based Parkinson's Disease Foundation.

Devastated Parkinson's patients and their supporters suspect that GDNF fell victim of today's more litigious environment--and that is only one drug out of thousands being developed by Amgen and other companies.

Drugmakers deny they are taking risk-averse actions that keep their products out of the hands of patients. Still, they are taking note of the shifting environment. Last month, the Pharmaceutical Research and Manufacturers Association announced that it had developed a new advertising code that called for manufacturers to better balance the risk and benefits of the drugs they directly advertise to consumers.

Hakan Edstrom, president and chief operating officer at Valencia's Mannkind Corp., said he has seen a change in expectations over the years. With its first drug candidate--a powdered form of insulin administered by inhaler--entering late-stage safety trials, both in-house and outside lawyers monitor each stage of the drug's development.

"Certainly that would not have been the case 20 years ago," said Edstrom. "You want to spend as much as possible on product development but you also have to devote much more resources to defending yourself or building legal defenses around what you do in the development stage, just in case. It can become very expensive for a company like ours."

Proactive or reactive?

Amgen spokeswoman Mary Klem notes that "patient safety is Amgen's first priority and continues to be a priority even after a product received FDA approval."

Indeed, GDNF isn't the first experimental drug that Amgen pulled during human trials. In the late 1990s the company discontinued work on two late-stage drug candidates, including a treatment for Lou Gehrig's disease, for reasons similar to those cited for GDNF.

When Amgen decided to stop clinical trials for GDNF, Chief Executive Kevin Sharer was quoted as saying he was "heartbroken" by the drug's apparent failure, and that stopping the study was the most difficult decision he had made since taking the helm there in 2000.

Until a few years ago, Amgen had largely avoided controversy over safety. It became the world's largest biotech company, largely on the success of two drugs, Epogen, taken by cancer and renal failure patients to counter anemia, and Neupogen, taken by chemotherapy patients to fight infection.

At first, there was little competition and few safety questions. But the company began to feel the heat of the changed environment in the drug industry. Three years ago, reports surfaced that Eprex, a version of Epogen licensed from Amgen by Johnson & Johnson and sold in Europe, was resulting in the death of some patients.

Studies showed that a different stabilizer Johnson & Johnson used to manufacture Eprex led to an immune response that led to a severe form of anemia. A similar drug sold by Roche Holding AG caused similar fatalities. The problem caused Johnson & Johnson to add a warning to its prescribing information in 2003 and send a letter to physicians last August.

Amgen for years had discounted the possibility that Aranesp, its second generation of Epogen, could cause similar deaths. But in January it issued a letter to physicians warning that high doses of anemia drugs, including Aranesp, may be dangerous to cancer and kidney disease patients.

Jon Fisher, who manages around the $22 billion Cincinnati-based Fifth Third Asset Management, a private equity fund, said he sees the actions of Amgen and other drug companies through the prism of litigation.

"The drug companies are seen as the bad guys with deep pockets," said Fisher, whose fund holds both Merck and Amgen shares. "Companies see lawsuits as the risk of doing business these days because we live in a litigious society."

Reducing risk

It's not the only time Amgen has reacted strongly to possible risk exposure.

Last February, the Food and Drug Administration demanded that the company pull a TV ad for the psoriasis treatment Enbrel because regulators considered it misleading. The ad, which showed models in bathing suits with clear, exposed skin, claimed psoriasis sufferers could get the unsightly disease "off their back" with regular injections of the drug. The FDA found that the ad minimized the risks while significantly overselling the drug's benefits.

With Vioxx and other anti-inflammatory painkillers so heavily advertised, the industry trade group last month published new voluntary, direct-to-consumer advertising guidelines.

The guidelines suggest that companies submit ads to the FDA before they are aired, that claims be supported by "substantial evidence" and that the spots balance benefits and drawbacks, among other changes.

Amgen, after getting slapped by the FDA over Enbrel, not only signed on but went further, pledging it would not air advertisement until it received specific "'pre-clearance" from the FDA.

Risky Business

Mark Schannon is a risk communications specialist and head of Schannon & Associates in McLean, Va. He explains why it is so difficult for drug companies and other large organizations to react well when they under attack in the court of public opinion.--Deborah Crowe

Question: Are drug companies more or less likely to mishandle such a crisis than other companies?

Answer: One of the characteristics of a pharmaceutical company is that it is a science-based company. People tend to be more thoughtful, they take time. What happens in a disaster is that things move very, very rapidly and you're often working with inadequate information, conflicting information, claims and charges, and you're asking people who have spent their entire lives being deliberative to immediately turn on a dime and start making judgments based on inadequate data. It just goes against all their training.

Q: So is there something drug and other companies can do?

A: When someone is angry or frightened or injured, what they want to hear is empathy, sympathy and concern. That's very, very hard for both companies and health care professionals to do, particularly when lawyers get involved, because they'll argue that you run the risk of damaging your court case.

Q: How much information should drug companies release in these situations?

A: The more you withhold, the more you're considered guilty. So you have to get the information out there, acknowledging that, "We don't have all the facts. This is what we know and we'll tell you more when we know it." People are incredibly tolerant of an honest response.

Q: What's the problem with saying as little as possible?

A: Well, the lawyers will say we'll fight this out in a court of law, where you're innocent until proven guilty. When you're attacked in the media you're guilty until proven innocent. If it's a big enough issue, by the time a pharmaceutical company like Merck gets to the courtroom, the court of public opinion has already judged them guilty and the pool of people from which the attorneys are going to pull the jury has already decided they're guilty.

COPYRIGHT 2005 CBJ, L.P.
COPYRIGHT 2005 Gale Group

Drug reverses Parkinson's brain damage


Ian Sample, science correspondent
Saturday July 2, 2005
The Guardian


An experimental drug for Parkinson's disease has been shown to trigger new nerve growth in the brain, the first time any treatment has reversed the brain damage caused by the condition.
Neuroscientists at Frenchay hospital in Bristol made the discovery when they examined the brain of a patient who took part in a trial of the drug GDNF four years ago. All five patients on the trial showed dramatic improvements.

Seth Love, a consultant neuropathologist at the hospital, examined the brain of a 62- year-old patient who had been on the trial but recently died of a heart attack. He found that nerve fibres in a region of the brain called the putamen had regrown. The loss of these fibres, and the chemical dopamine they produce, leads to Parkinson's disease.

Tests showed that the drug improved patients' control of their movements by between 50% and 80%. Also, they have experienced no deterioration since treatment stopped six months ago.
"This is the first time that any treatment at all has been shown to reverse the disease process. All the other drugs have just treated the symptoms," said Professor Love, whose study is published in the journal Nature Medicine.

But the finding does not mean a new treatment for Parkinson's disease is on the horizon. Amgen, the US company that owns GDNF, withdrew the drug last year amid concerns over its safety and efficacy.

Helen Garner of the Parkinson's Disease Society said the trial was encouraging. "This only based on one person though, and there are 120,000 people with Parkinson's disease in Britain.

NOVEMBER 18, 2002

SCIENCE & TECHNOLOGY

A Direct Hit to Parkinson's?
Infusing GDNF shows promise for brain-cell regeneration


For the victims of brain diseases, the golden hope is that scientists will figure out how to make damaged cells deep inside the brain regenerate. If this magic capability could be extended to the frayed neurons of patients suffering from Alzheimer's, stroke, Lou Gehrig's disease, or Parkinson's, their brains might restore themselves, much like skin that heals after a cut.

For Parkinson's sufferers, this dream may be moving toward reality thanks to the revival of a drug written off as a failure just three years ago. A clinical trial at the University of Kentucky is currently treating 10 Parkinson's patients with a bioengineered protein, called GDNF, using a radical new drug-delivery method that sends it deep into the part of the brain where Parkinson's originates. There, a constant supply is administered by a pump implanted in the chest. So far, GDNF seems both to shield healthy brain cells from the disease and cause damaged cells to regenerate.

After just a few months of testing, says Kentucky investigator Greg Gerhardt, there is evidence of improvement in patients. In addition, British doctors reported last April that a similar trial in Bristol, England, improved muscle control of all five patients tested within a month of treatment.

These results, while preliminary, were welcome news for Amgen Inc. (AMGN ), the world's biggest biotech player and the only maker of GDNF. In the late 1990s, Amgen injected the protein into the brains of a number of Parkinson's patients. The drug showed no positive effect, and in 1999, Amgen managers dropped it from their development program. Doctors now believe the trial failed because GDNF never reached the region of the brain affected by Parkinson's. Amgen's enthusiasm cooled, but academic researchers at several institutions were convinced that GDNF held promise and kept working on their own. The University of Kentucky team, along with British neurosurgeon Dr. Stephen Gill, who led the Bristol study, figured out the new delivery method used in the current tests. Several other research centers are drawing up plans for similar trials.

The Kentucky scientists received a $5 million grant from the National Institute of Neurological Disorders & Stroke (NINDS), a division of the National Institutes of Health, to fund their trial. They also persuaded Amgen to collaborate. Today, Amgen CEO Kevin W. Sharer calls GDNF "one of the most promising products" in the company's pipeline, and Amgen is planning clinical trials of its own. Sharer cautions that GDNF is still in a very early testing phase: "We don't want to give false hope, but if this proves to be a success, it will be a wonderful advance."

Even a modest advance would be fantastic. Parkinson's is a progressive disease of unknown cause that affects as many as 1.2 million people in North America. The illness destroys the cells in a portion of the brain called the substantia nigra that is responsible for the production of dopamine, a chemical involved in muscle control. As the level of dopamine gradually drops, the disease's characteristic tremors start. These grow violent as the illness progresses and are accompanied by stiff limbs, frozen facial muscles, and eventually, rigid immobility. While generally not fatal, Parkinson's is gruesomely debilitating. Most victims are over 50 when the disease strikes, but about 10% are under 40; actor Michael J. Fox first experienced tremors when he was 29. There is no cure, only treatments to alleviate symptoms, which lose effectiveness over time and can have severe side effects.

Scientists have hoped that GDNF might provide relief ever since its function was discovered in 1993. GDNF stands for glial cell line-derived neurotrophic factor, a protein produced by the connective tissue, or glial cells, between the neurons of the central nervous system. Animal studies indicated early on that GDNF can not only halt but reverse the damage caused by Parkinson's. But GDNF is a large molecule that cannot be absorbed through the stomach or penetrate the protective blood/brain barrier, ruling out pills and shots. That seemed to leave only one option: delivering it directly to the brain, a risky venture in human patients.

In early Amgen trials, doctors injected GDNF into the lateral ventricle, a fluid-filled portion of the outer brain. The theory was that the fluid would carry the drug deep into the brain. Instead, says Gerhardt, director of the University of Kentucky's Parkinson's research center, GDNF stuck to the walls of the ventricle. Gerhardt and Donald M. Gash, who runs the university's magnetic-resonance-imaging center, spent five years trying to come up with a better way.

The result is a complicated delivery system built around a Medtronic Inc. (MDT ) implantable pump called the SynchroMed, in use since 1988 to administer chemotherapy and painkillers. For the Parkinson's trial, a small catheter is threaded into the substantia nigra using MRI coordinates to precisely map the route. The catheter is attached to a tube that runs under the skin, down the neck, to a SynchroMed implanted in the chest. About three inches in diameter, the pump contains four weeks' worth of the drug and is programmed to maintain a constant flow to the brain. It is refilled each month through a port attached to the pump.

Gerhardt says it's too early to draw conclusions since the first human patient began treatment only in May. However, in the October issue of the medical journal Brain, Gerhardt and Gash report that rhesus monkeys with Parkinson's showed a significant reduction in symptoms within three weeks of treatment--without any detectable side effects. Autopsies revealed a partial restoration of the dopamine-producing cells, indicating that brain cells could be prodded to repair themselves. An accompanying editorial called this "the first demonstration that GDNF infused directly into the brain" is effective in restoring dopamine function.

Still, many drugs over the years have proved effective in animals only to fail in humans. "GDNF is really promising," says Diane D. Murphy, program director of the neurodegeneration group at NINDS. But she is not convinced that infusion is the best approach. "You need constant, ongoing infusions, and that's a problem," she says. "We need a less invasive delivery method."

To that end, NINDS is funding a large, multicenter study that will investigate the use of gene therapy as a way of getting GDNF into the brain. Jeffrey Kordower, research director at the Research Center for Brain Repair in Chicago, was one of the pioneers of this method. He uses an inactivated virus to carry a gene into cells of the brain, which it prods into producing more GDNF. In Kordower's studies, monkeys with Parkinson's that underwent gene therapy performed at near-normal levels a week after treatment. The genes remained active up to eight months after injection, and again, dopamine-producing cells were restored.

Researchers are also trying to develop stem cells that would turn into GDNF-producing cells when placed in the brain. But both gene therapy and stem cells present serious safety issues--recent human trials of both methods in other diseases have produced disastrous side effects. Consequently, human trials are still years away. For now, the direct-infusion method is the most promising. If it works, says Gerhardt, the same procedure could potentially be adapted to treat a variety of brain diseases. Now that scientists understand that brain cells can regenerate, there may finally be a glimmer of hope in treating the horrible ailments that destroy them.

By Catherine Arnst in New York, with Arlene Weintraub in Los Angeles







Copyright 2000- 2007 by The McGraw-Hill

MARCH 22, 2004

SCIENCE & TECHNOLOGY

Amgen Opens The Secret Curtain


The biotech leader will host analysts and investors to drum up excitement for its pipeline -- and its stock. Will it work?


Amgen Inc. (AMGN ) is used to its perch at the pinnacle of biotechnology. Its $8.4 billion in sales last year dwarfed those of its nearest competitors. Yet when it comes to innovation, Amgen is no highflier. Its best-selling drug is its first one, Epogen -- an anemia treatment launched in 1989. So when Roger Perlmutter joined Amgen as head of research three years ago, his first mission was to recharge its innovation engine.

He filled its labs with experts in everything from cancer to brain diseases. And he set out to license promising molecules from other biotechs -- something Amgen had shied away from before. "This is not your father's Amgen," he swears. Perlmutter's message has yet to register with Amgen's most skeptical constituency: Wall Street. The American Stock Exchange Biotech index has skyrocketed 70% in the past 12 months. Yet Amgen's stock has crept up just 13% in that time, to $63 -- despite $2.4 billion in profits last year and a 51% jump in sales.

What's keeping investors on the sidelines is the nagging question of whether or not Amgen has enough important products in development to maintain strong growth."We need to see that the research pipeline has both breadth and depth," says Kris H. Jenner, manager of T. Rowe Price Health Sciences fund (PRHSX ).

Analysts may be surprised to learn just how broad Amgen's pipeline really is. Traditionally, the company has been secretive about its research, but Perlmutter and CEO Kevin W. Sharer have decided that it's time to lift the curtain. On Mar. 23, Amgen will stage its first-ever "research and development day" for analysts and investors, who hope to hear some concrete data on Amgen's lesser-known experimental drugs.

TARGETING PARKINSON'S. One frontier the company has explored is diseases of the brain and nervous system. Its most promising drug is a protein, GDNF, that is now in Phase 2 trials to treat Parkinson's disease, which afflicts roughly 1 million Americans. In the trials, GDNF is pumped directly into the part of the brain where the disease originates. Neither patients nor doctors know who's getting the drug, vs. a placebo -- but some of the main investigators say it's already obvious. "One of my patients had severe tremors in both arms, and now he's normal," says Michael Hutchinson, assistant professor of neurology at New York University, one of the test sites. "I don't think that's a placebo." Although Amgen won't comment on future plans, doctors say it may start a pivotal Phase 3 trial by yearend.

In pain treatment, as in Parkinson's disease, Amgen has been all but silent about promising developments. Perlmutter, a veteran of Merck & Co. (MRK ), says Amgen may soon be ready to start clinical trials for a drug to treat neuropathic pain, which occurs when injured nerves send faulty signals to the brain. For some patients, even the lightest touch can be excruciating. Such pain is common in the elderly and in people with diabetes -- making it one of the most hotly pursued targets in the pharmaceutical industry.

In each new endeavor, Amgen will be racing against some formidable rivals. For example, in the field of inflammation, both Amgen and its biggest competitor, Johnson & Johnson (JNJ ), are targeting an enzyme called p38. What makes this molecule so promising is that it may be responsible for touching off several inflammatory signals. So a drug that can disarm it may prove more effective than current products, such as Amgen's blockbuster Enbrel, used to treat rheumatoid arthritis. J&J paid $2.4 billion last year to acquire Scios Inc., whose first p38 drug is in Phase 2 trials.

J&J's purchase of Scios is just the latest chapter in a legendary rivalry between the pharma giant and Amgen. Ever since 1985, when Amgen handed J&J most of the rights to its flagship anemia treatment, the two have been engaged in a bitter marketing battle. Lately, Amgen has been gaining: Sales of its new, long-acting version of the drug, called Aranesp, more than doubled in the last quarter of 2003, to $500 million. Sales of J&J's drug, Procrit, fell 12% in the same period. Still, with assets such as Scios working in J&J's favor, Amgen will have to fight harder. "J&J has gotten better, faster, and more determined," concedes CEO Sharer.

Small successes aren't the answer to Amgen's challenges. Wall Street yawned when the company won Food & Drug Administration approval on Mar. 8 for Sensipar, a drug to treat a parathyroid condition.

What Amgen sorely needs is to build up its expertise in major treatment arenas such as cancer. The company shines in a supportive role, providing anemia- and infection-fighting drugs to patients undergoing chemotherapy. Now it's working on a variety of molecules to treat the disease itself, including a colon-cancer treatment that Amgen is developing in partnership with Abgenix Inc. (ABGX ). Like ImClone Systems Inc.'s (IMCL ) recently approved Erbitux, Amgen's drug is an antibody that inhibits EGF, a protein that causes some cancers to grow. The difference is, Amgen's is entirely human -- unlike Erbitux, which contains some mouse proteins -- so it may cause fewer allergic reactions than ImClone's product. Amgen began enrolling a Phase 3 trial in January, but it has yet to reveal the study's design. Analysts hope to hear more details at the March meeting.

A cultural change will also help Amgen. Under Perlmutter, the company has scotched its not-invented-here attitude and scoured lists of early-stage drugs it could license from biotech startups. Last year, it entered into a $125 million licensing deal with Tularik Inc. (TLRK ), a South San Francisco company working on several cancer treatments. CEO David V. Goeddel says he was stunned when Amgen's Perlmutter agreed to visit the company in person, spending a day getting to know its projects. Then he quickly cooked up the deal -- fending off a large pharma company that was also interested in Tularik. "Amgen moved extremely fast," Goeddel says. The partners have already discovered two potential cancer targets, one of which could be ready for preclinical trials in 2005.

CEO Sharer fully supports Perlmutter's mission to stoke Amgen's pipeline. Sometimes he jets off at a moment's notice to join Perlmutter in courting licensing partners. "It's very important that Amgen stay nimble," he says. "We have to be fast, decisive, and flexible." And there's one more task: convincing investors that a well-oiled research machine will keep Amgen ahead of the pack.

By Arlene Weintraub in Thousand Oaks, Calif.





Copyright 2000- 2007 by The McGraw-Hill

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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Co-Inventor of Amgen's Aranesp(R) Technology Directs Worldwide Patent Strategy for Diffusion Pharmaceuticals' First-in-Class Oxygen Enhancing Therapeutics

CHARLOTTESVILLE, Va., Dec 21, 2007 /

PRNewswire via COMTEX/ -- Diffusion Pharmaceuticals LLC, a clinical stage drug-development company commercializing first-in-class drugs utilizing a novel mechanism of action that enhances oxygen diffusion, today announced that one of its key advisors, Mr. Thomas Byrne, was recently recognized as a co-inventor of the underlying technology of Amgen's blockbuster drug Aranesp(R) (darbepoietin alpha), a erythropoiesis stimulating agent
(US Patent No. 7,217,689).

Mr. Byrne, who is an Officer of Diffusion Pharmaceuticals and a member of its Board of Directors, has directed the worldwide intellectual property strategy of the Company since its inception in February 2001. His experience includes in-house counsel positions within both Genentech and Amgen.

"We are exceptionally fortunate to have such an experienced pharmaceutical development executive with scientific acumen and expertise in related intellectual property law leading our worldwide patent strategy and helping to guide the company," says David G. Kalergis, Diffusion Pharmaceuticals' Chief Executive Officer.

About Diffusion Pharmaceuticals LLC

Diffusion Pharmaceuticals LLC is a clinical-stage drug-development company commercializing a family of first-in-class drug candidates to treat serious or life-threatening medical conditions. These proprietary small molecules use a novel method of action to enhance oxygen diffusion to oxygen deprived (hypoxic) tissue. Potential clinical applications include critical care uses such as trauma, hemorrhage, stroke and heart attack, and cancer as well as chronic conditions such as cardiovascular disease, respiratory disorders, anemia and peripheral vascular disease. Enhanced diffusion of oxygen into hypoxic tissue has an important application in oncology by improving the efficacy of radiation therapy in cancerous tumors. The Company's first Phase I clinical trial for its lead molecule, trans sodium crocetinate (TSC), shows the drug is well-tolerated in healthy human subjects at doses significantly higher than the estimated efficacious human dose. Clinical trials will begin in 2008 in peripheral vascular disease patients suffering from intermittent claudication and in cancer patients undergoing radiation therapy. Diffusion Pharmaceuticals, which is privately held, is located in Charlottesville, Virginia. For more information, visit http://www.diffusionpharma.com.

SOURCE Diffusion Pharmaceuticals LLC


http://www.diffusionpharma.com



Copyright (C) 2007 PR Newswire. All rights reserved

Just adding that Bob Suthers has since passed away of lung cancer, but fought for GDNF to the end.

Paula

in his memory ~

thank you -Paula