This Is MS Multiple Sclerosis Knowledge & Support Community

Shame its gone onto a new page!

Sarah

Ian,

I see what you are up to. Keep talking this drug down and the shares of Biogen and Elan will continue to fall. Then you buy up as many as you can afford, the drugs comes back on the market and is a blockbuster, share prices go up, you sell, HarryZ becomes a millionaire. Sorry to have exposed your plan.

Ian (the artist formely known as Bromley)

The day I would buy shares in Biogen/Elan would be the day hell freezes over Unless, that is, I was a Biogen upper exec and had the ability to sell my shares before they plummeted as what happened in February!!

Harry

Wednesday, October 05, 2005

The Oregonian

MS drug worked wonders

I was disappointed by the tone of the article, "Promising drug's fate unclear" ( Sept. 28 ) Tysabri is the most promising drug to date for multiple sclerosis sufferers. Unfortunately, you were unable to find a patient to interview who had huge success with the drug -- such as my mother.

She, too, was on the drug for only one short month. However, in that one short month, we (her family) saw drastic improvements in her health.

With just one infusion of the drug, she was walking better, talking better, thinking more clearly and didn't fall once.

She was given a little taste of what life could be like again because of this drug, only to have it ripped away.

I give the manufacturer, Biogen Idec, credit for putting patient safety first and withdrawing the drug on its own. It is very encouraging that only three patients came down with progressive multifocal leukoencephalopathy.

To make a comment to the U.S. Food and Drug Administration about Tysabri, e-mail the FDA at ocoshi@oc.fda.gov. In the subject line, it should read "Tysabri Advocacy Group."

The more feedback the FDA receives about this drug, the better chance MS patients and their doctors can make the informed decision as to whether this drug is appropriate for their treatment.

CHRISTY COOKSEYCoos Bay


©2005 The Oregonian

http://www.oregonlive.com/printer/print ... xml&coll=7

She, too, was on the drug for only one short month. However, in that one short month, we (her family) saw drastic improvements in her health.

With just one infusion of the drug, she was walking better, talking better, thinking more clearly and didn't fall once.

Now if this MS patient had taken some kind of alternative drug and got the same results, the vast majority of MS docs would say that it was nothing but the placebo effect and all in the patient's mind!!

I give the manufacturer, Biogen Idec, credit for putting patient safety first and withdrawing the drug on its own. It is very encouraging that only three patients came down with progressive multifocal leukoencephalopathy.

I guess the writer wasn't aware of how much money the upper Biogen execs made by selling their stock just before they pulled the drug! And encouraging that only 3 patients got PML (and 2 died).!!! I guess as long as you weren't the 3 patients.......

The more feedback the FDA receives about this drug, the better chance MS patients and their doctors can make the informed decision as to whether this drug is appropriate for their treatment.

Perhaps the writer should have said the more "scientific" feedback the FDA gets, the better decisions can be made by patients and docs. It all goes back to a drug being rushed out the door for profit and ending up with the results we have today.

Harry

HarryZ wrote:

She, too, was on the drug for only one short month. However, in that one short month, we (her family) saw drastic improvements in her health.

With just one infusion of the drug, she was walking better, talking better, thinking more clearly and didn't fall once.

Now if this MS patient had taken some kind of alternative drug and got the same results, the vast majority of MS docs would say that it was nothing but the placebo effect and all in the patient's mind!!

Harry

Maybe. Here's an alternate hypothesis: The story about the one-short-month miracle cure simply isn't true. I would point out that, in addition to Biogen executives who sold stock at exactly the right time, there are others who still have strong financial incentives to see the drug return to the market. That fact provides another good reason to be especially wary of miracles.

Reed

17 October 2005

Elan and Biogen Idec Announce TYSABRI(R) Safety Evaluation Findings in Crohn's Disease and Rheumatoid Arthritis Patients; TYSABRI Safety Evaluation Complete; No New Confirmed Cases of PML

DUBLIN, Ireland & CAMBRIDGE, Mass.--(BUSINESS WIRE)--Oct. 17, 2005--Elan Corporation, plc (NYSE: ELN) and Biogen Idec (NASDAQ: BIIB) announced today that findings from their safety evaluation of TYSABRI(R) (natalizumab) in patients with Crohn's disease (CD) and rheumatoid arthritis (RA) resulted in no new confirmed cases of progressive multifocal leukoencephalopathy (PML). The companies have previously reported that findings from their safety evaluation of TYSABRI in patients with multiple sclerosis (MS) resulted in no new confirmed cases of PML. Three confirmed cases of PML were previously reported, two of which were fatal. The TYSABRI safety evaluation is now complete.

On September 26, 2005 the companies announced that they submitted a supplemental Biologics License Application for TYSABRI to the U.S. Food and Drug Administration (FDA) for the treatment of MS. The companies also recently submitted a similar data package to the European Medicines Agency.

More than 1,500 CD and RA patients from clinical trials were eligible for the safety evaluation. A total of 88% of these patients participated in the safety evaluation. In total, 98% of the patients participating in the evaluation had a neurological exam by a consultant neurologist and an MRI exam.

On February 28, 2005, Biogen Idec and Elan announced that they voluntarily suspended TYSABRI from the U.S. market and all ongoing clinical trials based on reports of PML, a rare and potentially fatal, demyelinating disease of the central nervous system.


http://www.elan.com/news/full.asp?ID=768099
.

You know, it is obivious that Harry's wife won't take Tysabri, for whatever reason. But if you think this is such a horrible, possibly fatal, out there all by itself kind of drug, then watch TV and listen to all those drug advertisements. Shoot, even Viagra can cause death if not taken correctly. Take a hard look at Betaseron when it came out. Phenominal drug for MS but with very little history as to how it could effect you. They probably still don't know if the CRAB's will cause cancer down the line. It will boil down to the MSers that live on the cutting edge a little. Anything for the hope of some improvement.

Amelia,

My wife wouldn't take Tysabri now for one very good reason....she has SPMS and Tysabri has no effect at all on that kind of MS. There are other reasons as well but they are irrelevant at this time.

As for other drugs being dangerous as well....of course they are and there is always a danger in taking a drug with various risks involved. But most of these drugs, including Betaseron as you mentioned, were researched for a long time, especially their safety aspect. Tysabri, unfortunately, didn't follow that standard route of time and was rushed out the door. Heck, Biogen didn't even finish their two year Phase III trials before requesting FDA approval. THAT is my main beef with this drug because if they had completed the two year trials, the drug would not have likely been approved so soon and thousands of MS patients would not have started on the drug for one or two months and then had it pulled from under them.

At least now, after all the reviews and further research, the docs and patients can make a far more informed decision as to whether they want to use it. And the docs will have a better understanding of what to look for when monitoring their Tysabri patients.

Harry

The following letter to the editor in this month's NEJM asserts that the two Tysabri / Avonex patients who contracted PML should not have been diagnosed as having multiple sclerosis. The authors pose a fascinating question: "Is it possible to misdiagnose subclinical nonfatal cases of PML as multiple sclerosis in patients who are not obviously immunosuppressed?"

An interesting letter, but it is just a conjecture on the part of the authors. Anyway, happy reading:

To the Editor: According to the established definition of multiple sclerosis,1 the condition in the patient described by Kleinschmidt-DeMasters and Tyler (July 28 issue)2 should not have been diagnosed as multiple sclerosis. Apart from the unusual clinical findings, no oligoclonal bands were detected in two separate examinations of the cerebrospinal fluid, and repeated magnetic resonance imaging (MRI) scans obtained over the course of several years showed new and enlarging, but never enhancing, lesions. The most convincing argument against a diagnosis of multiple sclerosis is the neuropathology: no lesions that are characteristic for multiple sclerosis were detected. The patient described by Langer-Gould et al. in another article in the same issue3 may also raise concern about the diagnosis of at least "typical" multiple sclerosis. One to two oligoclonal bands in the cerebrospinal fluid would have to be considered negative,4 and repeated MRI scans would not show enhancing lesions. Therefore, it does not seem appropriate to conclude that patients with multiple sclerosis may be at risk for progressive multifocal leukoencephalopathy (PML) owing to treatment with natalizumab and interferon beta-1a. Is it possible to misdiagnose subclinical nonfatal cases of PML as multiple sclerosis in patients who are not obviously immunosuppressed? Further investigations of JC virus infections should extend our knowledge of this scenario.


Thomas Berger, M.D., M.Sc.
Florian Deisenhammer, M.D., M.Sc.
Innsbruck Medical University
A-6020 Innsbruck, Austria
thomas.berger@uibk.ac.at

http://content.nejm.org/cgi/content/sho ... ?query=TOC

MetsFan,

I'm sure HarryZ will have a view so I will await his response.

I have a more general issue and would welcome any views from others.

The JC virus has been identified as the cause of PML - a demyelinating disease. Has the JC virus been ruled out as a possible cause / contributor to MS?

Bromley

Bromley, you asked:

Has the JC virus been ruled out as a possible cause / contributor to MS?

I don't know if JC virus has been ruled out as a possible cause or not, but this abstract, Detection of JC virus DNA in cerebrospinal fluid from MS patients concludes:

The finding of JCV DNA in the CSF of MS patients suggest that JCV could play a role in the triggering and/or in the maintenance of MS aetiopathogenic process, and therefore it should be taken in consideration when monitoring this disease.

Sharon

Bromley, there are several studies of JC virus in multiple sclerosis patients (you can type in "JC Virus" and multiple sclerosis into scholar.google.com), but I have not seen that establish causality.

With regards to Harry Z, I look forward to his comments. But please note that I label the letter as a conjecture, and as such, the odds are that it will not be proven to be true. It is interesting reading, nothing more.

Bromley,

I'm sure HarryZ will have a view so I will await his response.

Don't I always have a view on Tysabri

Prior to the introduction of Tysabri as a treatment for MS, most of us had not heard of PML and didn't have a clue what it was. The CRAB drugs along with other immunosuppressive drugs as well had been used for over 10 years and to my knowledge, there were no known cases of PML among these patients. Then, within a very short period of time, 3 cases of PML resulting in 2 deaths and one severely disabled patient show up.

The Crohn's patient who died had been on immunosuppressive drugs prior to using Tysabri had not used those drugs for several months prior to actually receiving the Tysabri. The only common element with all 3 patients was Tysabri so I feel that is far too much of it just being a coincidence. Tysabri obviously has some connection here but the researchers haven't been able to determine yet what that may be.

What we are seeing now as the research intensifies into Tysabri and PML is all kinds of speculation and theories. Sort of the horse following the cart!! If you read the many messages that Deb wrote in her theory of the dangers in using Tysabri, you have to know that if Deb sent this info to Biogen and the NMSS, the researchers involved with Tysabri had to have known about this ages ago. They must have been aware of PML and its consequences. Yet, despite this and the fact that MS docs such as Dr. Steinman warned Biogen as well, Biogen/Elan STILL rushed this drug to the early approval process with the blessing and approval of the FDA. Getting early, very positive trial results from two Phase III trials after one year is one thing but to jump the gun and get approval so quickly before you have finished all the trials is another. And Biogen/Elan and MS patients everywhere are paying the price for that action.

I too had previously heard that Anita Smith did not have MS and should not have been in the Tysabri trials. You can bet her litigation lawyers are very aware of this and the situation only adds to the confusion surrounding the entire Tysabri matter. What we do know is that thousands of MS patients have been left hanging in limbo over Tysabri and the researchers are working overtime to try and figure out just what happened. And I'll say it again...had Biogen/Elan only followed their original plan and not got greedy when they saw the potential revenue from Tysabri, today's confusion with Tysabri would likely have been avoided. Unfortunately there is more unknown about this drug than known and that has to change before Tysabri becomes a viable therapy for MS patients.

Harry

Well, isn't that article a new twist on an old theme!?

The fact is, people are misdiagnosed as having MS a LOT, and they don't have it (or any other serious neurological disease) at all. NOR do they have PML, either.

Keep it simple.

Deb

Further to my post above, following are additional letters to the editor in the same issue of NEJM dealing with Tysabri and PML. No resolutions to be found here – just an interesting exchange:



To the Editor: Kleinschmidt-DeMasters and Tyler described a patient with multiple sclerosis and PML that developed after she received natalizumab treatment. However, some of the findings in this patient are uncommon in multiple sclerosis. The absence of contrast enhancement in the MRI studies that were performed — almost a rule in patients with PML — is uncommon in multiple sclerosis.1 The lack of intrathecal synthesis of IgG is unusual in multiple sclerosis, although it is frequent in PML.2 Moreover, an autopsy study found no multiple sclerosis plaques but only PML lesions. Therefore, the pathological findings did not support a diagnosis of multiple sclerosis, which raises some questions. Can initial PML mimic multiple sclerosis? Was PML the only disease in this patient? To our knowledge, PML with a relapsing–remitting course has not been described. To clarify whether PML may have a relapsing–remitting course, it is necessary to study the cerebrospinal fluid in patients with relapsing neurologic disorders to rule out this disease. This seems particularly important for patients with suspected multiple sclerosis with atypical findings, such as early mental symptoms or an absence of oligoclonal bands. If it is demonstrated that PML can have an initial relapsing–remitting course, the risks of natalizumab treatment3 should be reevaluated.

José C. Álvarez-Cermeño, M.D.
Jaime Masjuan, M.D.
Luisa M. Villar, Ph.D.
Hospital Ramón y Cajal
28034 Madrid, Spain




"Drs. Kleinschmidt-Demasters and Tyler reply: We appreciate the comments of Drs. Berger and Deisenhammer and Dr. Álvarez-Cermeño and colleagues. Our involvement with this case began only post mortem; we were not involved in this patient's initial clinical evaluation, diagnosis, and treatment. The clinical and laboratory data presented were supplied by the patient's treating physician and supplemented by the Biogen company representative. Unfortunately, in some instances only the original MRI reports, not the actual scans, were available for independent review.
A variety of diagnostic criteria for multiple sclerosis have been proposed, including the widely accepted criteria of McDonald et al.1 These criteria do allow for the diagnosis of multiple sclerosis to be made solely on clinical grounds in a patient with two or more attacks and objective clinical evidence of two or more lesions. Criteria specific to MRI can provide supportive evidence of the dissemination of lesions over time; this criterion can be satisfied by the appearance of new T2-weighted lesions on appropriately spaced sequential scans. Oligoclonal bands on evaluation of the cerebrospinal fluid and enhancing lesions as shown on MRI are found in the majority of patients with definite multiple sclerosis; however, their presence is not absolutely required for diagnosis, nor does their absence completely rule out a diagnosis of multiple sclerosis.

We cannot resolve whether the absence of multiple sclerosis lesions at autopsy reflects obliteration of a limited number of multiple sclerosis plaques by the widespread and extremely destructive PML lesions, sampling error, or the presence of an alternative disease process. With regard to this last possibility, we believe it is unlikely that a chronic indolent or relapsing–remitting form of PML was the sole disease that this patient had or that it was responsible for this patient's symptoms early in her clinical course.

Our report, in combination with the others published in the same issue of the Journal,2,3 clearly indicates that natalizumab is associated with an increased risk of PML in patients without other recognized risk factors for this disease. The common denominator in all three reported cases, regardless of the underlying disease, was treatment with natalizumab.2,3

We hope that ongoing studies will clarify the pathogenesis of this disorder, including the viral factors and specific host factors responsible, and also the mechanisms by which natalizumab facilitates induction of PML.


B.K. Kleinschmidt-DeMasters, M.D.
Kenneth L. Tyler, M.D.
University of Colorado Health Sciences Center
Denver, CO 80262 "


"Dr. Langer-Gould and colleagues reply: The clinical history of our patient does not support the notion that subclinical cases of PML are masquerading as multiple sclerosis. To clarify, our patient had typical relapsing–remitting multiple sclerosis with clinical episodes of neurologic dysfunction for more than 20 years. He repeatedly had enhancing lesions in his brain and spinal cord during the 10 years before he was randomly assigned to the natalizumab trial, as well as a typical periventricular enhancing lesion concomitant with the first PML lesion. Finally, PML rarely affects the spinal cord.
We agree that the case in Colorado that was reported by Kleinschmidt-DeMasters and Tyler is troubling. The clinical criteria for multiple sclerosis were recently revised to improve their sensitivity, with unknown effects on specificity. The revised criteria rely heavily on the presence or absence of lesions on T2-weighted imaging, which frequently occur in patients with migraine,1 such as this patient. The natalizumab trial included patients with normal neurologic examinations (such as this patient), despite the fact that the risk of permanent disability in such patients is very low.2 These problems with the diagnostic criteria for multiple sclerosis and the entry criteria for clinical trials need to be addressed.


Annette Langer-Gould, M.D.
Scott W. Atlas, M.D.
Stanford University
Stanford, CA 94305-5405
annette1@stanford.edu


Daniel Pelletier, M.D.
University of California, San Francisco
San Francisco, CA 94143 "