Well that happened too, but that's not what I'm talking about. A Trial Doc informed Biogen of PML being a factor on the 9th of Feb, if I recall it correctly.

Damn I wish I could find it.:confused:

Sally,

I know what you mean....the article we are both referring to gave the name of the trial doc and the date he stated that he informed Biogen. (Feb 9) I've spent a lot of time searching the net for this article but still no success.

Harry

Tysarbi trial
 

Is this the page you are looking for?


Stanford Doctors Spotlight Fatal Flaw In Multiple Sclerosis Drug Trial
05 Mar 2006

When Anita Louise Smith enrolled in an experimental drug trial in 2002 in Colorado, she had a diagnosis of multiple sclerosis but no symptoms and was looking to reduce the chances of being ravaged by the disease. Last year, she died at the age of 46 from an infection linked to the drug.

This tragedy - recounted in an article in the March 4 issue of The Lancet by two Stanford University School of Medicine neurologists - serves as a telling case study of what can go wrong in clinical trials. In their article, Annette Langer-Gould, MD, and Lawrence Steinman, MD, warn of the pitfalls of testing a drug with unknown side effects in patients who would do fine without the drug.

The drug in question is natalizumab, which has the brand name of Tysabri. In November 2004, the U.S. Food and Drug Administration fast-tracked its approval for use in multiple sclerosis patients following promising results seen early in two clinical trials. But within months of the approval, some patients taking the drug had developed a rare infection - progressive multifocal leukoencephalopathy, or PML - and Smith and one other patient had died.

Langer-Gould, a clinical instructor in neurology, treated a patient who was part of the clinical trial and developed PML after taking Tysabri; the patient survived. But that experience, coupled with an examination of Smith's case, prompted Langer-Gould to approach Steinman about writing an article that would examine the appropriateness of testing a drug on people with no evidence of the disease and who are not disabled at the time of the trial.

"We are arguing that people with no disability should probably not enter into a clinical trial or be recruited into clinical trials, because where is the potential benefit to them if nothing is wrong?" said Steinman, professor of neurology and neurological sciences and of pediatrics.

"This situation represents a systemic problem," said Langer-Gould. "It is not just one company being a rogue, doing something out in left field."

Langer-Gould and Steinman argue that if a drug has a known risk of death, it should only be used on patients who are likely to suffer severe disability from the targeted disease - and for whom there are no other options. In other words, those who have tried all the other available therapies. That is almost the reverse of what happened in the Tysabri trial, which excluded the most severely affected patients.

"A big mistake was made in these trials that, in my opinion, is easily preventable," said Langer-Gould. "All they need to do is tighten up entry criteria into multiple sclerosis clinical trials and we could avoid similar types of problems in other trials."

Multiple sclerosis results when the immune system attacks the protective myelin sheath surrounding nerve cells, causing them to misfire and leading to loss of motor control and possibly paralysis. Tysabri appeared to block this effect and, after the first year of the two-year clinical trials, did not appear to cause more infections.

Steinman was involved early on in the development of the drug, publishing on its effects in 1992. Even then, he had suspicions that the drug's mechanism of action - blocking the entry of immune cells into the nervous system - might also make patients more vulnerable to infections. Indeed, PML is an infection that usually affects people whose immune systems are compromised.

"It was a shocking development that a drug that had so much promise and so many potential benefits ended up causing two deaths and one very serious injury," said Steinman. "It is kind of a cruel Greek drama, something that may be more beneficial than anything yet developed for multiple sclerosis, but yet may be far more dangerous than those other approved drugs."

The FDA withdrew Tysabri only three months after its approval. The FDA is now considering re-approving the drug. On March 7 and 8, an FDA advisory panel is meeting about the possibility of bringing back Tysabri as a single therapy (in the trials, it was combined with another drug).

"I predict it will come back with really hellacious warnings," said Steinman. "I think the right course would be to have it undergo more testing, but I don't think that is practical or fair to patients; they ought to have the opportunity to decide with their physicians if they are willing to take the one in a thousand risk of dying."

But Steinman and Langer-Gould expressed reservations about the drug returning to the market. They noted that its effects, while impressive, are in general not much better than what is seen with other available drugs: The risk of relapse dropped from an average of two relapses every three years using other approved multiple sclerosis drugs to one every three years with Tysabri.

"Do you want to expose someone to the risk of death for eliminating one relapse every three years?" said Steinman. "I say no."

"I'm not sure if it is wise to re-approve it," added Langer-Gould. "The question is, will the FDA rise to the occasion and admit their mistake and try to prevent future mistakes or are they going to ignore it?"

###

BROADCAST MEDIA CONTACT: M.A. Malone at (650) 723-6912 (mamalone@stanford.edu)

Stanford University Medical Center integrates research, medical education and patient care at its three institutions - Stanford University School of Medicine, Stanford Hospital & Clinics and Lucile Packard Children's Hospital at Stanford. For more information, please visit the Web site of the medical center's Office of Communication & Public Affairs at http://mednews.stanford.edu/

Contact: Mitzi Baker
mabaker@stanford.edu
Stanford University Medical Center

Article URL: http://www.medicalnewstoday.com/medi...p?newsid=38837
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This is a good article but unfortunately not the one we are looking for. The one we want quoted an actual trial doc who said that he had advised Biogen of his patient's PML on Feb 8 or 9 and that they hadn't acted on it until two weeks later. It's out there somewhere.....just a matter of finding it.

Thanks for your efforts though...they are much appreciated.

Harry

In my search, I found this interesting report that seemed to have been swept under the rug by Biogen/Elan, in getting approval for the re-introduction of Tysabri.

The source link is at the bottom of this article. Some good stuff there.

Sally


September 02, 2005
Analyst Report Forecasts Some Choppy Waters for Return of Tysabri

FDA Adverse Event Reports Show Tysabri May Be Tied To Other Serious Side Effects
On August 29, 2005 The Wall Street Journal ("WSJ") reported that a list of adverse event reports made to the FDA related to the Tysabri included several rare infections, some of which were fatal, apart from the rare brain infection called progressive multifocal leukoencephalopathy.

Tysabri, a multiple-sclerosis drug, was withdrawn from the U.S. market on February 28, 2005 due to increasing concerns that Tysabri use could cause progressive multifocal leukoencephalopathy ("PML"). At that time, the companies responsible for Tysabri, Elan Corp. of Ireland and Biogen Idec Inc. of the U.S., said two patients with multiple sclerosis ("MS") taking Tysabri had contracted PML, with one patient dying from PML. The two companies later confirmed a second fatal case of PML in a patient using Tysabri to treat Crohn's disease, a gastrointestinal disorder.

The new WSJ article is based on information obtained through a Freedom of Information request made to the FDA by an pharmaceutical industry analyst at Morgan Stanley, Steven Harr. Following an analysis of the Tysabri data which he received from the FDA, Mr. Harr issued a report on August 25, 2005 describing some adverse event reports for Tysabri which showed a number of Tysabri patients had died of rare infections. "We're not trying to put a death knell on Tysabri, but there are signals in there that something's going on. It's important for patients and investors to know," Mr. Harr said in an interview.

A spokesman for Biogen immediately dismissed Mr. Harr's report, stating that Biogen and Elan had performed a detailed safety analysis of Tysabri. The companies' analysis, according to this spokesman, found no statistically significant differences between serious adverse events with patients given Tysabri and patients given a placebo in several clinical trials. "We have an enormous amount of information in our hands," the spokesman said. "The [FDA's adverse event reports] database is a limited tool."


According to the WSJ article, by staff reporter Sylvia Pagan Westphal:

The analyst's report describes seven non-PML deaths in patients taking Tysabri that "appear to be related to immunosuppression." One death was owing to pneumocystis pneumonia, an infection that only patients with severely debilitated immune systems get; another was because of herpes encephalitis, a rare infection of the central nervous system. Four other deaths were possibly caused by sepsis, an uncontrolled infection that spreads through the body. The report mentioned that the FDA database contained "numerous" accounts of serious, nonfatal infections that "suggest again that the toll from Tysabri extends beyond PML."

Despite the problems that may be posed by these possible new side effects, Mr. Harr predicted that Tysabri has a good chance of returning to the market. In fact, Biogen and Elan said earlier in August 2005 that they hope to get the drug back on the market. The companies announced, then, that they had screened more than 2,000 MS sufferers who took Tysabri in clinical trials for signs of PML. According to the companies, the screening produced "no new confirmed cases" of PML.


Lars Ekman, executive vice president and president of research and development at Elan, had this comment:

Patient safety remains our top priority.... We are committed to finalizing the safety evaluation for Crohn's disease and rheumatoid arthritis, which is progressing well and on track to be completed by the end of the summer. We look forward to working with regulatory authorities to determine the path forward for Tysabri.

Given these new adverse event reports of other serious infections in Tysabri users other than the rare brain infection PML, there seems to some choppy waters ahead for Biogen and Elan as they try to get Tysabri back on the market.
(Posted by: Tom Lamb)

http://www.drug-injury.com/druginjurycom/side_effect_infections_necrotizing_fasciitis_sepsi s/index.html

That is pretty creepy :eek:

Sally,

I can remember reading this article back then and the typical Biogen reply in that there was no statistically significant difference between the Tysabri users and those on placebo. The question I had at the time was what the heck was in the placebo to cause those patients the number of infections that they ended up with?!!

Makes you wonder just how much "skewing" goes on in these trials!

Harry

The thing that strikes me, is that PwMS are still not being told all the facts. It may be only 1 in 1000 fatalities due to PML, but there were 7 others who died from other infections, after being on Tysabri, and those deaths should certainly be in the count.:mad:

So Deaths attributed to T are approx. 3 in 1000 or 1 in 333. That changes the risk factor in a big way, IMO.:eek: There are also several who have suffer infections and are still surviving, including one with PML. This should also be part of the deciding factors, to use Tysabri.

There are severeal Neuros just not wanting to take the chance on T with their patients....Maybe they have considered the true statistics/risks here. I applaud their restraint, on behave of their patients.

Remember, this is not a cure and from what I've learned, doesn't just keep the bad T-cells from crossing the blood brain barrier, but also the good, leaving your immune system unable to fight off ANY infection, for some people.

Sally,

You hit the nail on the head when you said that the docs MUST tell their patients of ALL the risks if they want to try Tysabri. If after that is done and the patient still decides to go ahead with the drug, then that is the patient's perogative and right to do.

In my opinion, good marketing/advertising always trumps good science (in the short term, anyway) and there aren't too many pharmas better at it than Bigoen. Before Tysabri got approved the first time, you only had to follow how Biogen's marketing people hyped this drug, continually quoting the high numbers in both reduction of lesions and "risk" of disease progression over the placebo patients in the trials. The dangerous side of the drug was all but ignored and minimized when information about the infections surfaced. Heck, the press had to use the freedom of information act to obtain this detrimental data.

For sure, Tysabri is a drug were the users must be carefully and constantly monitored for these dangers. I just hope there aren't any more "surprises" with it as more and more MS patients start to try it.

Harry

There will be surprises of course. However, there will also be miraculous improvement. It is so hard to know where the balance is.