This Is MS Multiple Sclerosis Community: Knowledge & Support

Dr. Steinman! Wait a minute! Isn't he THE Lawrence Steinman?

And nobody listened to HIM? Oh, now how can that be explained away?

Deb

Ptwo,



It's a good thing that you didn't post this info about Dr. Steinman before they pulled Tysabri. You likely would have been accused of "fear mongering" and spreading "rumours" by quoting one disgruntled Neurologist

Harry

Yeah, and quoting the very neuro who STARTED research into VLA-4 antagonists (back in the 80s, wasn't it) in the first place!

And you're so right, Harry. They could put a real twist to that one!

(Sorry, I couldn't resist.)

Deb

Here is another newspaper article that I came across today.

Harry

______________
By Ricardo Alonso-Zaldivar and Denise Gellene, Times Staff Writers


WASHINGTON — A multiple sclerosis drug pulled off the market after a patient died was approved by the Food and Drug Administration even though a prominent neurobiologist and a top medical journal had questioned the drug's safety.

When the FDA gave the drug, Tysabri, so-called fast-track approval in November, "there was already somebody out there saying 'Whoops,' " Arthur Levin, director of the New York-based Center for Medical Consumers, said Tuesday.

"It's a legitimate question to ask if the FDA paid any attention to those concerns, and if not, why not?"

Dr. Lawrence Steinman, a Stanford University professor and an MS specialist, said he repeatedly wrote and spoke about the potential for serious immune-system side effects with this type of drug. The MS patient who died while taking Tysabri suffered from progressive multifocal leukoencephalopathy, or PML, a rare central nervous system disease usually seen in AIDS patients.

"I was really worried this would cause opportunistic infections," Steinman said. "I was largely on the sidelines, issuing jeremiads and negative predictions that this would lead to troubles."

Steinman — whose career as a developer of drugs for multiple sclerosis makes him a potential competitor to Tysabri's manufacturers — began raising his concerns long before the New England Journal of Medicine published an editorial in early 2003.

At that point, Tysabri was in what is known as a Phase II trial in which a relatively small number of people taking the drug were studied for six months. The Journal said that "firm conclusions about safety … must await the results of much larger" studies.

Those larger, Phase III studies haven't yet been completed. Nonetheless, the drug was approved under an accelerated program for breakthrough medicines that the FDA sees as offering extraordinary benefits to patients.

"This was a product that absolutely fit the criteria for accelerated approval," said Dr. Douglas Throckmorton, acting deputy director of the FDA's Center for Drug Evaluation and Research. "The trials were well planned and well conducted, and the outcomes suggested a product with important scientific advances."

Throckmorton said he didn't know whether agency scientists saw an article Steinman wrote last summer in the journal Science, in which he warned that "there is at least a theoretical concern that recipients of the therapy would become generally compromised in their ability to fight infection."

But Throckmorton said he was confident that FDA scientists knew about, and considered, such a theoretical risk. He stressed that in almost 3,000 patients involved in clinical trials before Tysabri was approved, there were no cases of PML or life-threatening immune system reactions.

"It's clear that other drugs used for MS have effects on the immune system, and I'm sure the office thought about those same issues when they looked at this new entity," he said. "I am certain the division looked at that."

A spokeswoman for Biogen Idec Inc., which developed the drug with Elan Corp., said Steinman never met with the company to share his concerns.

"Our focus now is on patients," said Amy Brockelman. "Our concern is for their safety and that is what is guiding our actions."

Some in the biotechnology industry said something clearly went wrong in the agency's expedited process, which has been criticized in the past for rushing drugs to the market before they have been thoroughly scrutinized.

"The fast-track process, in the situation that exists, obviously is not working right," said Joseph Panetta, president of Biocom, an industry group in San Diego, where Biogen ranks among the largest biotech employers. "It needs to be looked at …. Something about the process needs to be restructured."

MS affects some 400,000 Americans and leaves about half of its victims permanently disabled. The cause of the disease is unknown, but scientists believe it is rooted in a malfunction of the immune system, which prompts immune system cells to attack the brain and spinal cord.

The FDA approved Tysabri based on results from the first year of two Phase III clinical trials, each of which was designed to last for two years. The first-year results of those trials showed that the drug reduced the frequency of MS attacks by as much as 66%.

The drug is believed to work by binding to certain immune system cells, preventing them from traveling to the brain where they can cause damage. The fast-track clearance was hailed as a breakthrough for MS patients, who had not seen a new drug in a decade. Usually the agency requires the completion of clinical trials before granting approval.

On Feb. 17, Biogen announced that it had completed one of the two-year clinical trials and that the results confirmed the positive one-year outcome.

But the next day the makers of the drug reported to the FDA that one patient taking Tysabri as part of the studies had developed PML and that there was a second suspected case.

There is no known effective treatment for PML, which often leads to death. One of the patients died Thursday, four days before the drug was recalled.

Biogen previously said the patient had died Feb. 18.

Company executives said they learned of the two patients after its pre-dawn Feb. 17 announcement about the trial, but refused to be more specific.

Researchers familiar with Tysabri said they weren't surprised to learn that patients had become infected with the deadly virus. Emmanuelle Waubant, a neurologist at UC San Francisco, said PML didn't show up in the one-year data because such infections take long to develop.

"In patients with HIV, it takes several years of having their immune system compromised to develop this virus," she said. "It is not surprising it took two years in each [Tysabri] case," she said. "There is a reason why these studies were designed to take two years."

Waubant said she would not have approved the drug without seeing two years' worth of data, but she was loath to criticize the FDA because the drug also appeared beneficial. Waubant was one of the academics who helped conduct the clinical trial for Biogen and Elan.

"You are always more intelligent after the fact," she said. "It is hard to blame the FDA."

Stephen Miller, a microbiologist at Northwestern University who has collaborated with Biogen on studies in the past, said the body's immune cells were a poor target for an MS drug. Tysabri "blocks the ability of [immune cells] to get from the blood vessels to the tissue to fight infection," he said. "In my opinion, that is not the way to go."
________

Harry~

Thanks for pasting that last article. It was terrific; very clearly and intelligently writen, really right on-the-money (pun intended ).

What newspaper was it from anyway? I saw "Times", but don't know which "Times".

Flora,



To tell you the truth, I don't know. I picked up the article on the net and posted it here. The story originated in Washington but that's all that was there.

Harry

That's OK, Harry. I found it. (Good old Google )

Your article was from "The Los Angeles Times", by Healthcare reporter Ricardo Alonso-Zaldivar, with Denise Gellene, another staff writer. Here's the link to the article:
http://www.latimes.com/news/printedition/la-fi-biogen2mar02,1,4360139.story?ctrack=3&cset=true

.

Great find, Harry (and flora!)

Right about now, though, I'm fit to be tied practically.

Number one. Ok, maybe Dr. Steinman didn't write to the FDA, but I did!! Remember the extreme "heat" I took over THAT one? Right down to having to have that thread locked and removed from this site. That's probably why the reporter I talked to was so interested in the fact that I had written to the FDA, and not only that, I told him how I had asked the FDA to "confirm receipt of my communication", and the big dummies DID confirm receipt of it! So...........what are they going to do? Say they didn't get any objections to the fast tracking of Tysabri? I can hardly wait until the FDA says their little "piece" in the press! They might want to be careful. (And at the time of my postings back in November that caused all the hoopla, (remember Harry?), I had not heard or read about anything any other high profile doctors had been publicly saying. This is all news to me as we speak.)

And the NERVE of Biogen saying Steinman never "met with the company to share his concerns". As if saying nobody contacted THEM? Excuse me? WE did! Arron spoke to "somebody" at Biogen who was "supposed" to answer our questions regarding Tysabri, remember? They never showed up, did they? The NMSS even showed up here once, so they could see we don't "bite". Where did Biogen disappear to? And Art Mellor from Boston Cure reads and posts on this website. He has Biogen people on his Advisory Board! Tell me they didn't likely know about the concerns that were being expressed on this message board alone. Yeah, right.



That's what I want to know, also. I provided them with some biological evidence for my concern, also. I came from the angle and focus of the fertility and birth defects issue and mentioned the word "thalidomide" in order to try to get their attention. The words "possible infection running rampant" that I also posted in November, I KNEW wouldn't have gotten their attention at all. Biogen had already uttered that word, which effectively put the focus off of that risk. But we knew that, also, here on thisisms (i.e. that infection could run rampant). OUR concerns are POSTED and dated! Right, Harry? And I did mention in my letter to the FDA about other safety concerns with Tysabri. Let's see 'em try to get around THAT one!

And you know what? And I'm going to say this again one more time. VLA-4 is necessary for implantation of the fetus in the womb. There is plenty of biological evidence to still indicate that further research into these area(s) of possible severe "safety concerns" with Tysabri needs to be done, also.

NOT in an attempt to try to keep the drug off the market completely. That's not my point. My point is that there are SEVERAL safety concerns with Tysabri that the public needs to be "fully informed" about........FULLY informed............before agreeing to take it.

I will say that and defend our rights for full disclosure until the day I die.

Deb

http://www.thisisms.com/modules.php?nam ... sc&start=0



First, look at the dates of these findings that BIOGEN found.

encephalitogenic means: tending to cause encephalitis - an encephalitogenic strain of a virus



I found and posted these (among other research findings by other researchers) back in November, 2004 - BEFORE the approval of Tysabri.

I have no clue in the world how Biogen can even utter one single word starting with "we didn't know........". Yes, they did.

Deb

EDIT: And I'm sorry, but if the FDA "experts" missed these, also, during their investigations for approval, then we ARE in a precarious situation. (In my humble opinion.)

I think what some of you are overlooking is the fact that Tysabri helped far more people than it hurt. Of course, anytime someone dies, it's very tragic and cannot be overlooked. I'm sure there's a possibility that we will see more deaths, but I find it unlikely.

I've read far to many stories of people with astounding improvement while on Tysabri and even some from folks who were on A & T, are doing much better with no ill effects from the combo.

I believe what we'll see in the end, is that, these folks who became il and or died, we're also on steroids, along with the combo therapy and it was just to much of a wallop to thier immune system. I believe they may have been very weak to begin with.

We see deaths in trials all the time. I don't believe that Biogen knew of these pml dx's & death prior to the release.

All of the rumors floating around are scaring people needlessly. I think everyone should get the facts from thier doctors, not from someone playing doctor or super nurse on the internet.

I will most likely use Tysabri as my MS treatment when and if it becomes available again.

coolycat

Coolycat,

It really doesn't matter how many people a particular drug helps, if it has the ability to kill someone and the company who makes it hasn't done all the research required prior to introducing it to the public, you have a VERY big problem!!

At the moment, Biogen doesn't know what the source of the problem is and until they do, Tysabri won't be allowed. There is all kinds of speculation at the moment but certainly no scientific facts available. Some prominent MS docs had warned Biogen about the problem that is happening now and they chose to push ahead full speed anyway! The litigation lawyers are already having a field day with this and it is likely to get worse.

So until Biogen gets the PML problem sorted out (if that's possible) and any other issues related to tampering with certain T-cells that enter the brain, Tysabri will be unavailable to anyone. And the time frame for this to happen unfortunately simply isn't known at this time.

Harry

Lawyers, Schmaywers.

The class action suit is on behalf of the investors, not the patients.

That's funny. How and why is it then, that Harry knew about it WAY before the release from Biogen. If Harry knew, believe me, I can't help but "suspect" that Biogen knew. (Forgive me, but the accusations and chances of Harry just making that up out of thin air or spreading "rumors" doesn't cut it anymore, does it?) And besides, it's not just "us" on this website asking about it. It's the SEC. You might want to consider voicing that opinion and your support to the SEC, then, and help Biogen Idec/Elan that way.



Well, there's "one". (Sorry for the sarcasm.) But wait.......you said "most likely". For someone so positive about everything, is that "doubt" that you are expressing after all? And what if you don't meet the very probable new and narrowed down "criteria" for taking Tysabri when and/or if (as you yourself eloquently stated) it comes out again?



And as Harry and I (to mention just two) are always so respectfully "asked", is that statement simply based on rumor or from unknown "sources", or can written verifiable "proof" be provided?

Actually, there's no need to answer.

Deb

I'm sorry. Where did Harry say "class action suit"? I'm certain that unless some very quick and very confidential settlements with the deceased families and the "ill" are made, you will see lawsuits, all right.

And that's just to start with.

Hi, Harry!

Deb

EDIT: Oh, yea, and Harry said "litigation" lawyers, not "securities" lawyers.

SECOND EDIT: My apologies. I had forgotten a word in a sentence during my typing, so I made the appropriate typographical error correction is all.

Well, so far the only mention of litigation that I have seen has come from people involved with using Tysabri. That's not to say that the investors won't jump on the band wagon!

Like I have said, this mess is only starting and will get far worse before the dust settles. When people die and immense amounts of money are lost very quickly, the reaction usually comes very quickly....as Biogen is finding out.

Harry