http://www.suburbanchicagonews.com/h...ONS_S1.article

Here's one of the guys that would make you a believer in GDNF.

Fight of his life
Man helping to lead way in Parkinson's debate

October 5, 2006
By TOM POLANSEK SUN-TIMES NEWS GROUP
Before receiving an experimental drug called GDNF, Steve Kaufman could not hold a nail because his fingers were so immobilized by Parkinson's disease.

Just months after his treatments began in 2003, however, he was able to renovate the kitchen in his Algonquin home. Later, in an even more ambitious project, he added a deck on to the rear of the house.
"I was feeling so wonderful," Steve, 52, said. "It was like getting my life back."
But the euphoria didn't last long. Less than a year after he started on GDNF, officially known as Gilal-cell-lined derived neurotrophic factor, the drug's manufacturer, Amgen Inc., canceled the clinical trial in which Steve was enrolled.
» Click to enlarge image
Steve Kaufman of Algonquin and his wife Maggie sit on the deck Steve built while participating in a drug trial to treat his Parkinson's disease. The deck was built in the summer of 2004 after the treatments began. Maggie said Steve's body allowed him to do things while he was being treated with the trial drugs.



That meant he no longer had access to the medicine that had taken away pain in his legs, stopped much of his shaking and allowed him to resume normal activities.


Steve and his wife, Maggie, did not take the news lying down. Instead, for the past two years, they have networked with other GDNF patients from around the world and lobbied Amgen hard to make the drug available again.

The determined couple have contacted the company's top executives, met with officials from the Food and Drug Administration, and shared Steve's story with Michael J. Fox, the actor who became an advocate for Parkinson's patients after being diagnosed with the disease.



For all Parkinson's patients


Although GDNF drastically improved Steve's quality of life, the Kaufmans say they no longer are fighting just for themselves. They now fight for every person stricken with Parkinson's, a degenerative disorder of the central nervous system that affects the control of muscles.

"The drug's effective," Maggie said. "We know it's effective. Everyone that sees Steve knows it's effective."
Indeed, it has become the Kaufmans' mission to connect those suffering from Parkinson's with a drug that may improve their lives.

Steve and Maggie, who describe themselves as religious, feel they were put on Earth to put GDNF into the hands of those who need it. Other Parkinson's patients regularly call their home and send them e-mails to discuss the battle for GDNF or hear about Steve's story.

For many doctors and Parkinson's patients, Steve has become an inspiration.

In February, the couple attended the World Parkinson's Congress in Washington, D.C. To illustrate the effectiveness of GDNF, the Kaufmans showed pictures and a video of Steve building the deck.
Steve became a minor celebrity at the conference. "People wanted to meet me," he recalled.

One of those people was Robin Elliott, executive director of the Parkinson's Disease Foundation, a private, New York-based organization dedicated to advancing Parkinson's research and assisting victims of the diseases.

Elliott recalled being impressed by Steve's ability to function. "My reaction was that this was one healthy, happy man," Elliott said.


Quick results



In the clinical trial, GDNF was administered to patients as a liquid through pumps that were implanted in their abdomens. Catheters were then fished under the patients' skin to take the medicine to their brains.
Steve's surgery took place in 2003, and lasted six hours. He was one of three trial patients in the Chicago area. Others were in New York, Kentucky and Canada.

The benefits of the surgery and medication became apparent relatively quickly. Six weeks after the first injection, Steve was shaving, and he noticed his facial muscles had relaxed. Formerly frozen, his face became animated once again. The pain he felt in his legs also melted away slowly. By February 2004, Steve said he "really started to feel good."

Then came the news that Amgen halted the study. Although Steve was thriving, the company reported that tests showed the drug was ineffective and could be dangerous.

"We were devastated," Maggie said. "A week before they took the drug away, I forgot he was sick."
Without the drug, the pain started to seep back into Steve's leg, although he still functions better than he did before the GDNF.


No
w what?



The Kaufmans asked Amgen to provide the drug to trial participants on the basis of "compassionate use." Amgen, thus far, has refused.

Amgen CEO Kevin Sharer said in a statement that company researchers spent several months reviewing the company's decision to halt GDNF clinical trials and concluded that it was for the best.

Many patients involved in the GDNF trial have had their delivery systems removed since the trial ended.

Steve, however, says he will keep his device in while he fights to get the drug-and his life-back. "We will not stop fighting until there is nothing to fight for," he said.

-The Elgin Courier News


Paula

Thanks for the article Paula..

As Ive posted many times..I met Steve at the WPC and talked with him about his experience with GDNF..At the time he hadnt received any GDNF in about 17 months, and was still functioning well..You couldnt tell by his appearance that he was an advanced Parkinsons patient prior to the treatments..What I saw was impressive..a miracle!..GDNF works, and I cant ever imagine Steve giving up his fight..because there will always be something to fight for..In spite of what Amgen says..In spite of the fact that judicial system ruled in favor of Amgen..The fact will always remain that Steve received significant benefits from the drug..I saw it myself, and there was absolutely no question about it..It gave me hope, but it also angered me to no end that the answer to our nightmare is so close..yet so far away

Steve

dear Paula,
I have been in touch with Steve Kaufman, he has the Spirit of a great overcomer!
He has a great story!

He has inspired me tonight, I needed to hear goodnews...

The People vs. Amgen

Clinical trial participants rarely sue pharma companies for discontinuing an unsafe drug. Here's what happened when two such cases were brought to court.

Jun 1, 2006
By: Todd E. Betanzos
Successful Clinical Trials Management


Most clinical trial lawsuits filed against pharma companies stem from allegations that the investigational drug harmed participants. But how often do you read headlines about clinical trial participants protesting when a drug study is concluded because of safety concerns? While patients often don't want to continue a clinical trial after a drug is pulled for safety, what are the implications for pharmaceutical companies when they do?

Such was the case in April and June 2005. Two separate groups of people who had been subjects in a Parkinson's disease clinical trial sponsored by Amgen, sued the pharma company in federal court for permanent injunctive relief and monetary damages. But unlike traditional clinical trial lawsuits, they weren't asking for compensation or damages. (Suthers, et al. v. Amgen and Abney, et al. v. Amgen). Instead, they wanted to force Amgen to continue providing them with the product.

The Clinical Trial

The cases involved a Phase II clinical trial to study the effects of a synthetic protein called glial cell line-derived neuroptic factor (GDNF), to which Amgen owned the rights. The study was designed to test whether GDNF would spur the growth of dopamine-producing cells and alter the course of Parkinson's disease (rather than simply masking its symptoms like currently available therapies). It began in 2003 and involved 34 patients at eight sites—including the Kentucky and New York sites where the plaintiffs participated. Prior to undergoing surgery to implant a pump, a necessary step to supply GDNF directly to the brain, each study subject signed an informed consent document. The consent provided that the study participants could elect to continue treatment for 24 months after the end of the study. But it also stated that investigators could withdraw a subject from the study if they found that the risk of continued participation outweighed the benefits, or if the sponsor decided to discontinue the study for a variety of scientific reasons.

At the start of the clinical trial, Amgen hoped to see a 25-percent increase in subjects' scores relative to placebo after six months of treatment. By June 2004, however, the group using GDNF showed a bit more than a 10 percent increase, while the group using placebo had a 4.52 percent increase. Seven of the 34 subjects showed dramatic improvement, but four of those seven had received placebo.

Since the results weren't up to Amgen's expectations, the company terminated all clinical use of GDNF in September 2004. It also cited two safety concerns: (1) the results of a primate study in which four of 44 primates given GDNF suffered cerebellar toxicity; and (2) the discovery that several human subjects had developed neutralizing antibodies. Amgen also cited lack of efficacy as a reason for discontinuing the study, stating that any positive effects experienced by the study subjects were from the placebo effect common in clinical trials for Parkinson's disease. Amgen consulted with FDA regarding the study's termination, and FDA agreed that the termination was reasonable in light of the scientific evidence.

The Litigation

Upon filing suit in Kentucky and New York federal district courts, both groups of plaintiffs asked the courts to issue preliminary injunctions forcing Amgen to continue providing them with GDNF. They argued that GDNF was beneficial to them, and Amgen had contracted to supply them with the drug as long as it proved beneficial. They also said that in undergoing the pump implantation surgery, they had acted to their own detriment, relying on promises made by Amgen. Those promises were enforceable pursuant to the law of promissory estoppel. That doctrine provided that Amgen promised they would supply the drug to the participants, and since they promised to, it would be unfair not to follow through with their promise. Finally, by unreasonably denying access to GDNF, Amgen was breaching a fiduciary duty it owed them. After conducting hearings, both courts denied the requests.

In their claims for breach of contract and promissory estoppel, the plaintiffs argued that the informed consent documents signed by study subjects constituted a contract and a promise on Amgen's part to continue treatment indefinitely with the investigational drug. They argued that, although the agreements were executed by the study subjects and the investigators (rather than Amgen itself), the investigators did so as Amgen's agents. Finally, the plaintiffs argued that Amgen was bound by the study investigators' statements that they would make decisions based on the patients' best interests, and that the subjects could continue to receive GDNF following the conclusion of the study if it proved safe and effective.

Both courts disagreed. Noting that the investigators, and not Amgen, executed the informed consent documents, the courts found that Amgen had not entered into any contractual agreement with the participants. Citing the express terms of Amgen's clinical trial agreements with the investigators—which provided that the investigators were independent contractors, and which structured the study so that the investigators would conduct it independent of Amgen—the courts also found no actual authority on the part of the investigators to bind Amgen in any way. Lastly, the courts found that Amgen had not said or done anything which might have clothed the investigators in apparent authority to act on its behalf.

In support of their breach-of-fiduciary duty claims, the plaintiffs argued that Amgen, working through the study's investigators, breached its fiduciary duty to ameliorate their pain and treat their illness with the best medicine available. However, the courts found no evidence that Amgen agreed its sponsorship of the study was undertaken primarily to benefit the participants. The courts further emphasized that the study was intentionally structured to foster independence and objectivity on the part of the investigators and their research institutions, thereby insulating them from any potential conflict of interest, which might arise from Amgen's involvement. For example, Amgen had not selected the subjects, met the subjects or known the details of the subjects' medical conditions. Given these considerations and the rigid FDA regulations, which govern the manner in which clinical trials are conducted, the courts found no factual or legal basis to impose a fiduciary duty on Amgen.

Having lost in both Kentucky and New York, the plaintiffs appealed each of the lower courts' decisions. Although the New York plaintiffs later withdrew their appeal, the Kentucky plaintiffs continued. On March 29, 2006, the 6th US Circuit Court of Appeals in Cincinnati, Ohio, found in favor of Amgen and upheld the Kentucky federal court's ruling.

The Implications

The courts' rulings in Abney and Suthers represent important victories for pharma companies. Current FDA regulations governing the conduct of clinical drug trials mandate the respective responsibilities of investigators, institutional review boards (IRBs), and study sponsors. And, while compliance with regulations may not always constitute an absolute defense to liability, it is an important component of the defense, arising out of a clinical study.

Those same regulations mandate that the study investigators must obtain the informed consent of each human subject to whom the drug will be administered, and that they are responsible for protecting the rights, safety, and welfare of subjects under their care.

Had the courts found a contract to exist between Amgen and the participants, or had they found that Amgen owed them a fiduciary duty despite the fact that research was conducted by independent researchers, further litigation against the industry would have resulted. Litigation would have continued, not only by participants wanting to continue receiving investigational drugs after a trial's end, but by study participants hoping to take advantage of pharma companies' heightened obligations mandated by FDA's regulations governing clinical trials.

Todd Betanzos is senior associate at Sedgwick, Detert, Moran & Arnold in Dallas. He can be reached at todd.betanzos@sdma.com