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I heard on Fox news this morning about another PML patient dying on Tysabri. They didn't elaborate, so was this the Chron's patient or another MSr?

Deb,

The more I read about these Tysabri trials, the more I shake my head and wonder what is going on!!!

Take care.

Harry

please read the story on the front page for more information on this patient. This is not a cut-and-dry Tysabri = PML case, it seems.

I agree Aaron. It sounded like the person was knocking on death's door before the Tysabri or pretty darn close to it. Any info on the type of transplant they got? Or are there other reasons you would take the immunosuppressant drugs for transplants?

for severe Crohn's (this person must have been in agony, poor soul), you might take these drugs as they are strong suppressors of the immune system. Just like the immune system (purportedly) attacks the CNS in MS, in Crohn's it attacks the lining of the digestive tract.

Arron,

Arron wrote:please read the story on the front page for more information on this patient. This is not a cut-and-dry Tysabri = PML case, it seems.

The problem, however, Arron, is that these cases are being discovered post Tysabri approval and now Biogen has to back-track and try and prove that Tysabri has had nothing to do with it. That is going to be a formidable and time consuming task. If only they had waited the standard two year period and then gone after the approval, Biogen could have approached the problem offensively as opposed to defensively as they now have to do. And every little problem that gets discovered takes another chunk out of their stock value!

Harry

Comments from an Pathologist / Virologist

"PLEASE READ AND UNDERSTAND

This current re-review assesses the risk of taking tysabri as it was given in the clinical trials - it is very easy to figure out if patients are becoming immunosuppressed and at risk for PML - all BIIB and ELN need to do is test patients for too much immunosuppression and tysabri can be safely administered with no risk of PML

But given the circumstances of this case and the other two tysabri should not be given in combination with other immunosuppressive drugs (remember the other two patients were part of a trial in which 9.3% of all patients took prohibited immunosuppressant drugs and that could have greatly increased there risk of PML)

This case in my opinion cannot in any way be directly linked to sporadic tysabri use - see below

My specialty is pathology and virology - and this reaction to this news is completely overblown this patient had too many other risk factors for PML given the

1) the patients age
2) the treatments that the patient had
3) the length of the treatment the patient received
4) the length of the disease and severity
5) the diagnosis of a tumor given the fact that JC virus can be found at a high rate in brain tumors
6) the small amount of tysabri given
7) the fact that tysabri treatment was only given in two spurts 3 months and 5 months separated by 9 months
8) the number of tysabri patients that have gotten 8 months of treatment is very large and not even a hint of immune suppression has been found in any of them
9) the fact that for PML to occur you need profound reduction in T cells or a complete T cell anergy to JC virus to get PML to occur and given that in the absence of prior immunosuppression this has never occurred in any tysabri treated patients given the dosing

And then remember this in order for PML to occur any patient needs a very low T cell count as occurs in AIDS, CLL, and certain leukemia or a complete lack of a T cell response as occurs with severe or long term treatment with immunosuppressive agents (which this patient had )

THAT BEING SAID ALL ELN AND BIIB HAVE TO DO IS TEST T CELL ACTIVITY IN PATIENTS THAT ARE RECEIVING TYSABRI - AS LONG AS T CELL ACTIVITY IS GOOD THEN NO PATIENTS WILL EVER GET PML

THIS TYPE OF TESTING IS VERY SIMPLE AND CAN BE DONE QUICKLY AND CHEAPLY

THUS BY TESTING PATIENTS TO MONITOR THEM BEFORE THEY BECOME IMMUNOSUPPRESSED ELN AND BIIB CAN SAFELY PREVENT PML IN ALL CASES - THUS BECAUSE OF ITS EFFICACY TYSABRI CAN STILL BECOME A BLOCKBUSTER DRUG YOU JUST NEED TO TEST PATIENTS FOR TOO MUCH IMMUNOSUPPRESSION

I WOULD HOPE THAT BIIB AND ELN HAVE ALREADY COME TO THIS CHEAP AND SIMPLE TEST THAT WOULD PROTECT ALL POTENTIAL TYSABRI PATIENTS FROM PML AND ALLOW THEM TO ENJOY THE SUPERIOR EFFICACY AND QUALITY OF LIFE THAT TYSABRI CAN AFFORD THEM "
.

Better.

That was a very good analysis of the this patient's problem but I ask the question again....why in the hell wasn't Biogen doing this kind of pro-active work in the Phase III two year trials as opposed to rushing for approval with the FDA? I and many others can answer that easily....they saw the $$$$ at the end of the rainbow!

They were cautioned and warned by more than one expert of the dangers of Tysabri but that didn't stop them. Full speed ahead! And can you imagine the level of trust that they have lost within the medical community as well as from many MS patients? I realize that hindsight is so very easy to apply in this situation but that's all Biogen had to do was follow the standard trial plan and they could have avoided this current mess. And in the process avoided the $ 17 billion drop in Biogen/Elan stock value.

Harry

Good to hear some encouraging news about the Tysabri. When Gary took Betaseron he had to have liver test OFTEN to monitor the drug. He had to be careful about other drugs that cause extra stress on the liver. Does Copaxon suppress the immune system? I don't think so, but I am no expert. I know someone knows the answer to that. Anyway, due to finances, we had already decided on using Tysabri ALONE, drop the Copaxon

BIOGEN IDEC AND ELAN

The Tysabri dilemma is continuing to haunt Elan (ELN) and Biogen Idec (BIIB) and will continue to be a cause for concern and skepticism as long as the investigation of the suspected link between Tysabri and progressive multifocal leukoencephalopathy, or PML is still ongoing. What is almost certain is that the investigation looks extremely thorough.

While some observers are jumping into conclusion, seeing only the negative impact on the two firms’ stock prices, scientists and advisor's involved in the investigation, or following up on it are interested in getting to the bottom of the story before issuing any statement of condemnation of Tysabri, or any other drugs, or combination of drugs.

Many other immunosuppressive drugs that are saving lives of millions of patients from detrimental diseases might also be considered suspicious. As a matter of fact, no medical expert has denied the possibility that drugs other than Tysabri might have caused PML and might have probably caused deaths in a small percentage of susceptible patients. Everything is possible at this stage and if they might have happened, such possibilities might have been either missed, or overlooked, when benefit was proven to outweigh the risk.

The announcement yesterday night that a third case surfaced, involving a sufferer of Crohn's disease, rather than multiple sclerosis, does not really lead to any specific conclusion at this time. Nobody has yet claimed with certainty that the side effect is related to the nature of the treated disease. No medical authority has yet concluded that patients suffering from neurological, or neurodegenerative diseases are more susceptible to developing the viral infection when taking the drug or a combination of drugs than those patients who are treated for other disease.

The fact that the two previous PML cases, involved sufferers of MS and the third new case involved a Crohn’s disease patients does not prove anything and does not entitled anybody yet to reach conclusions. Until the experts who investigate the whole problem on behalf of the two companies draw their conclusions, nobody else’s remarks and conclusions should be taken seriously.

Medicine is a very highly regarded profession and medical research and investigation have well established protocols and rules that aim at scrutinizing all the circumstances, all the variables and all the possibilities before issuing a statement. Medical investigators do not have the luxury to jump into conclusion as some lay people exposed to the media do. The only fact observed to date in the Tysabri story is that Biogen Idec and Elan are investigating all the circumstances that could lead to patients’ susceptibility for developing PML.

The two firms alone are conducting this investigation on behalf of all the biotech firms and the drug companies who sell immunosuppressive drugs, including chemotherapeutics and biological drugs that suppress immune system components, including, T-cell suppressors. You know what, the commonly used cortisone might have also been considered suspicious.
Yesterday’s declared case goes back to 2003. The case was misdiagnosed and the cause of death was misstated. The same might have happened to patients taking other drugs and other combinations of drugs.

No other company has withdrawn any drug from the market BIIB and ELN did. Another probability is that the number of patients developing the disease has remained so small that it was considered a risk that is much lower than the reward. Added also is the fact that very little is known about PM. That’s what might have helped PML to go unnoticed until the two firms stepped in and took the right decision of investigating the whole story.

We believe in medical capability and we believe that this investigation is the best thing to happen. We are optimistic about the outcome. We are almost certain that the investigation will go far beyond pointing the finger towards a drug or drugs as causing the infection. The investigation will bring a better knowledge about the virus that causes the disease. It will divulge the circumstances that lead a virus to transform from peaceful to pathogenic and, you know what? It investigation might bring new guidelines that can help the medical practitioners prevent this disease. It might come up with early diagnostic and preventing measures and even with treatments that are possibly existing and could turn the deadly condition into a treatable infection.

PROHOST RESEARCH
P.O.BOX 640 429
Oakland Gardens, Ny 11364

Medicine is a very highly regarded profession and medical research and investigation have well established protocols and rules that aim at scrutinizing all the circumstances

So why didn't Biogen/Elan follow the established protocol when it came to researching Tysabri?

Harry

An article from The Guardian (UK quality broadsheet) suggesting a sticky time financially for Elan following the withdrawal of Tysabri.

Elan attempts to cut costs as third patient contracts disease linked to MS drug

Heather Tomlinson
Friday April 1, 2005
The Guardian

Irish pharmaceutical firm Elan appears poised to announce a cost-cutting programme at the end of this month after another case of a rare brain disease was reported in patients taking its multiple sclerosis drug Tysabri.
Shares in the company more than halved yesterday to €2.40 - which makes a near-90% fall since the trouble with the MS drug began - on the news that a third patient had contracted a fatal nerve damaging disease, called progressive multifocal leukoencephalopathy.

The drug was withdrawn in February after two months on the market. Analysts said the fact that there is a third patient with the disease decreases the likelihood of its returning.
The loss-making company is reporting results at the end of this month and it is understood it will update investors on its cost-cutting plans.

There is also speculation it will look at selling off its two antibacterial medicines, Azactam and Maxipine, which Goodbody stockbrokers' analyst Ian Hunter thinks could bring in $350m (£185m), or its drug delivery business.

Elan has more than $1bn of debt to repay in 2008. Although it has cash on its balance sheet, it is heavily loss-making and had been relying on revenues from Tysabri to bring it back to profitability.
Analysts say it is likely that more expensive trials would be required before regulators considered letting the drug back on the market.

"We are reviewing cost structures as a result of recent events and will manage cash burn through aggressive cost control, both as it affects Tysabri and the rest of the business," said a spokesman.

Mr Hunter said investors are looking for a cost reduction programme, and the early stage drug work in Alzheimer's and Parkinson's is most vulnerable.

"Elan has been sticking with a large R&D budget and saying it is justified by [the success of] Tysabri, I think that will have to give way," he said.

Analysts were concerned that the third case of PML was in a patient on Tysabri alone, whereas the first two had been in combination with another drug. Merrill Lynch analyst Erica Whittaker said future Tysabri sales are "increasingly risky. Our valuation for Elan is negligible if Tysabri is permanently suspended," she said.

"If Tysabri never returns to the market, we believe Elan would not be able to repay more than $1bn debt due in 2008, and would continue to burn through its cash pile without substantial restructuring."

Tysabri had shown better results in MS patients than other drugs on the market, and had also been tried in people with Crohn's disease and rheumatoid arthritis. It works by suppressing the immune system in the brain, which is over-active in MS. PML is often seen in patients with Aids, where the immune system is suppressed.

Elan and its partner Biogen, a US drugs firm, are studying the 3,000 patients who have taken the drug to find whether there are more cases of PML.

http://www.guardian.co.uk/business/stor ... 47,00.html

I have quite mixed feelings about the whole affair but just something in me says, "Serves them right!" EDIT:: fixed a typo

John,

Regardless of how much many of us dislike the total financial situation that focuses on pharmaceutical companies, it is a fact of life. In the case of Elan, I believe it will be the finances that end up crippling the company, possibly for good!

Remember, it was Elan who initiated the earlier FDA approval process with the one year data from the two Tysabri trials that were being conducted in Ireland. ( I believe this is accurate but if anyone knows differently, please let me know) They had the most to gain from this and were a struggling company. The projected revenue from Tysabri was huge and Biogen's marketing department, one of the best in the business, did quite the job of making Tysabri out to be "the" drug for MS.

Biogen/Elan took the gamble and it looks like it is going to totally backfire on them. Biogen will likely survive because of other drug sales but Elan is walking on very thin ice. And, as usual, the MS patient is but a secondary concern.

Harry