Hi Boann,

The comment about the patients not believing they are worth it for no profit was concerning the overall, pervasive attitude[ and it's easy to see why it exists!] that you can't fight something as powerful as the largest bio tech and even an attitude of "why should we?" It is so competitive, it costs the companies so much money to produce a treatment - they have to do what they do - all true up to a certain point.

I believe we should fight even the largest bio tech in this type of circumstance, however, even if it is only to prevent it from happening again. Patient participants in this study, along with patient advocates, with the counsel of some of the researchers involved in the study, simply cannot see evidence of safety problems with this drug in humans. Some had been on it for almost 3 years.

Great lengths have been taken to check other primates involved in preclinical study [not by Amgen] - no adverse effects.

Other than antibodies, which Amgen will not confirm or deny were caused from dislodged pump/catheters, there have been NO ADVERSE EFFECTS in humans. I personally know one patient whose antibodies went away as soon as her treatments were halted. My personal belief, from everything i have researched, and that includes talking directly with most of the trial researchers pro and con regarding the halt, that the antibodies were not a major concern.

Humans do not need to be given the high dose that produced lesions in 4 monkeys. There have been no lesions in humans.

So here we have a substance, that granted is a bit of an experience to deliver - surgery to install pump and catheters, that patients have been taking for 3 years with NO ADVERSE EFFECTS, that some patients, from taking it, swear they have felt like they were cured, that has caused dyskinesias to go away, medication to be greatly reduced and some eliminated, and last but not least, which requires surgery far less risky than DBS and is regenerative, sitting on a shelf because Amgen says it isn't safe, it isn't effective, it's just placebo.

They will not release their toxicity reports, claiming they will be published. I will just mention here, that sloppy reporting gets rejected, then they have to rewrite, sometimes more than once before it gets published. We haven't gotten to that game yet that I know of; I don't think the results have been submitted to any journals yet.

Tonight in the UK, the GDNF trial participants, all of whom in Phase I showed improvement, are getting together for a reunion. We sent them a message of encouragement. If they care enough to do this, what does it say about their lives? What does it say about this treatment? They still want it back......they know it works.

Paula

Hello boann:
I've just stumbled across this website and have found your post. I can personally tell you much of what has been going on since the halt of the gdnf trial. My husband is one of the 34 patients who were in Phase II.

It's very interesting that the doctors are divided between their theory of whether or not GDNF works. The reality is, from a patient viewpoint, the drug DOES work. My husband has been off the drug for two years and nearly 3 months. His regression has been minor. Prior to GDNF I had to button his clothes and cut his food. He could not walk 1 block without falling along the way, the list could go on. After GDNF he has done many things, most of which has been in the newspapers already such as replacing my kitchen cabinets and building a deck on the back of my house, yes, holding a nail and hitting it with a hammer without hitting his fingers! We've done many things since however this summer he has build stairs for me and climbed a ladder and trimmed all 30 of our 15 foot tall bushes. He is not only stable but a fully functioning human being.

The patients, as well as caregivers, advocates and some of the doctors have been fighting and trying everything possible to convince Amgen they have a good drug. My husbands PET scans prove it. I truely believe, that the halt has more to do with the delivery system than the drug itself due to the high cost of the surgery and the management of the pumps. Dr. Perlmutter has made the statement in his speech at a California college that hospitals would rather see more knee surgeries than these sort of surgeries because they can move people in and out faster.

My husband had no difficulty whatsoever with the drug or the pumps. Some patients had catheters that migrated so they were not even getting the GDNF. So essentially, we go from 34 patients in the study to, in reality, 29 or 30. If 1/2 of these patients were on placebo, then essentially only 15 people were getting GDNF for the entire time. Is 15 people over a 9 month period of time a good enough sample to judge either the safety or efficacy for a population of 1.5 million in this country alone? Not a lot of common sense in that to me. Not only that but the primates were getting 10 to 15 times the dosage of humans. You take 10 to 15 times the dosages of Tylenol and I'm sure you'll have some nasty effects. Amgen didn't even take the time to consider the "Early Withdrawal" phenomenon which, I am told, is a high probability of why the monkeys developed lesions. So who is Amgen protecting? Certainly not the patients. If they would have ever taken the time to pay attention to the patients, they may have looked at the decisions made about GDNF in a different light.

very interesting to hear from one with personal experience, thank you maggie. i have a question, which dr. perlmutter are youu referring to? i'm curious because my neurologist is also named perlmutter.

Oyster,

Here's who Maggie is talking about:

http://www.amgen.com/about/leadershi...erlmutter.html

Hi Boann,
I will try to answer your questions that I am able to

You wrote:
3) why have studies for the last god knows how many years on whether or not levodopa is toxic to DAa neurons been deemed "inconclusive" ad nauseum while this study was deemed negative after 12 months with enough improvement in enough people to cause this much of a furor in a community that has been swallowing hope to no avail in the form of experimental drugs for the last 40 years?

5) i thought the study was halted due to antibodies and lesions in primates? how can a study that was not completed fail to achieve its endpoint? (must re-read your post)

Reply:
The phase II study was based on 6 months of data. After the 6 month double-blind placebo controlled trial, an open label study commenced - the placebo group could receive GDNF and the experimental group could continue to receive treatment. Even with the so-called “negative results,” at that point, Amgen was planning to continue on with a phase III trial. But in September 2004, they hastily ended all treatments due to “safety issues.” In addition to ending the phase II trials, they also stopped supplying GDNF to the 15 phase I participants in Kentucky and Bristol UK.

NOTE: 15 out of 15 of these patients reported continued improvement in their symptoms and no harmful side effects after 2-3 years on GDNF. The trial doctors at these centers, along with some of the phase II doctors, refused Amgen’s order to remove their patients’ pumps and catheters and kept them going with saline solution in hopes that Amgen would reinstate GDNF treatments. That hasn’t happened yet.

4) how far short of their endpoint of 25% improvement did they fall?

The primary endpoint in the phase II (placebo controlled) study was a - 25% change from baseline in the UPDRS motor score in the practically defined off condition after 6 months. This endpoint was determined by the amount of improvement seen in the phase I studies. The phase II experimental group improved their scores by a mean of -10%
(see Lang et al. Annals of Neurology 2006: 59: 459-466)

However these results and the phase II study design have been questioned and challenged.
According to independent analysis, the number of subjects (34) in phase II was much too low to ever have achieved a 25% improvement in scores in this type of study. Hutchinson, et al reports that the study was “underpowered “ and the results should be considered “inconclusive, not “negative.” (see: Journal of Neuroscience Methods. 2006 Jul 27; [Epub ahead of print] "GDNF in Parkinson disease: An object lesson in the tyranny of type II."

Additionally the study has been criticized because there were so many differences between the phase I and phase II design including type of delivery system, size of catheter, rate of delivery and GDNF dosages etc. that meaningful comparison between the 2 phases was not possible, Further studies were called for but could not take place because Amgen refused to provide their GDNF.

RE: Patient improvement:
You may have seen Maggie Kaufman’s posting in this thread
about her husband Steve, a young onset PWP, who was a phase II participant and had improved greatly after 9 months of treatment. Before GDNF he was in a wheelchair. I met Steve at the World Parkinson Congress in Feb. 2006. I honestly could not tell that he had Parkinson’s – and this was over 18 months after his treatment had been halted. Similar results have been reported by other phase I and II participants (see http://www.grassrootsconnection.com/...rticipants.htm for participants’ testimonies and www.pdpipeline.org for news articles.

You wrote:
7) what motivation would amgen have for manufacturing a reason to halt the study?
REPLY:
My guess is $$$$$$$.

did 60 minutes or one of the other news related programs cover the GDNF controversy awhile ago? seems to me, the news program showed footage of the vice president of Amgen at an Amgen conference stating that the delivery system for GDNF was too expensive and that there were not enough surgery suites manned by neurosurgeons to perform all the catheter implants required if the drug was marketed and used as in the trials. that another delivery system had to be developed, thus the drug was going to be pulled out of the trials. or am i making all this up???madelyn

You are right Madelyn, it was on 60 Minutes and Perlmutter was shown in that video. Ironically, he was not using it in the context that it was presented on 60 Minutes. In that video, discovered online by Jaye of this forum and delivered to 60 Minutes by Perry Cohen, Perlmutter was still pro-GDNF, and was showing proof of it with pictures of brains. He w as saying that they would go with GDNF IN SPITE of the fact that it would be difficult finding surgeons, operating rooms, and wouldn't be a moneymaker.

There's your media at work...lol....they didn't feature the context in which he was saying it.....instead they made it sound like he was giving reason not to go with it. In other words, they misrepresented him.

You can actually view Roger Perlmutter's presentation on GDNF at:
http://www.uctv.tv/search-details.asp?showID=8901

It's eyeopening! At about 38 minutes into the speech he answers a question about how much money Amgen could make on this. His reply is that although they don't expect GDNF to be a big money-maker for Amgen, they still would go ahead with its development because the company believes in "putting the needs of patients first." This was the part 60 minutes (otherwise a terrific report) left out.

I have spoken to one of the trial doctors who said that the surgery involved in the procedure to implant the pump and catheter is actully less complicated, less dangerous and easier to train surgeons to perform than DBS surgery, because they don't need to go as deeply into the brain.

I forgot to add that the date of Perlmutter's presentation was March 6, 2004 -6 months before the GDNF trials were halted. On the introductory web page it shows Dec. 2004 - this is an error. On the recording itself, the March date is given.

I wanted to send a short note as a clarification. My husband, Steve, who was one of the 34 GDNF trial patients was not bound to a wheelchair prior to GDNF. Actually, he could not walk for any great distances even when he was on but he was not at the point of a wheelchair. The pain in his legs were immense and his left ankle gave out all the time. Because of this, he took small, slow steps and he was bent over most of the time for stability. I'm sure it was hard for anyone who met Steve and the World Parkinsons Congress in February to imagine he was like this at all. I'm sure Linda can attest to this.

Maggie