BLOOMBERG ARTICLE

[OddDuck]

....and speaking of press articles, (weren't we somewhere? ), here is the one that the Bloomberg News did, after speaking with some of us. I believe, though, that they are continuing to follow this story as it all unfolds, and I'm pretty certain we haven't seen nor heard that last from them. (All in all, in my opinion, it's a pretty impartial rendering.)

Anyway, here 'tis, in case anyone was wondering what they ended up writing.

Deb

Elan, Biogen Shares Fall as 2nd Illness Is Confirmed (Update9)

(Adds closing share prices in seventh and eighth paragraphs.)

By John Lauerman and Michelle Fay Cortez
March 4 (Bloomberg) -- Shares of Elan Corp. and Biogen Idec Inc., the third-largest U.S. biotechnology company, fell today after a rare neurological disease was confirmed in a second patient taking their multiple-sclerosis drug Tysabri.

The second case may dash hopes that Tysabri, the first new type of
treatment for MS in eight years, will make an early return to the market after the companies withdrew it Feb. 28. The U.S. Food and Drug Administration, already under scrutiny over drug safety, faces criticism of the accelerated process that got approval for the drug last November.

Omar Khan, director of the MS Clinic at Wayne State University in Detroit and a Tysabri researcher, said the two patients developed progressive multifocal leukoencephalopathy, a fatal condition known as PML, after taking Tysabri and Avonex, another Biogen product, for two years.

``If there is an association, I think this drug is history,'' Kahn said in
an interview today. ``PML can't be a black-box warning disease when it is
invariably fatal.'' The FDA highlights its strongest warnings on drug labels in a black box.

Both PML patients, one of whom has died, were in their mid-40s with mild to moderate MS when they started in the trial. They were among 500 patients who have taken the drugs together for more than two years.

Merck & Co. recalled its Vioxx painkiller Sept. 30 after a company study showed that the rate of heart attacks and strokes among those taking it for 18 months or longer was 15 per 1,000 patients, compared with 7.5 for people on a placebo.

Lost Market Value

Shares of Elan, Ireland's biggest drugmaker, based in Dublin, have fallen 79 percent since the beginning of the week, wiping out $8 billion in market value. The stock dropped 1.10 euros today to 4.47 euros as of 5:13 p.m. in Dublin after trading as low as 4.25 euros, a 15-month low. American depositary receipts, each representing one share, fell 94 cents, or 14 percent, to $5.71 at 4:03 p.m. New York time.

Cambridge, Massachusetts-based Biogen's shares have lost 44 percent, or $9.8 billion. Today the stock declined $1.80, or 4.6 percent, to $37.53 at 4 p.m. New York time in Nasdaq Stock Market composite trading.

``Two cases from separate locations strengthen the link,'' said Goodbody Stockbrokers analyst Ian Hunter in Dublin, Ireland, in a research note.

Return to Market

Tysabri's developers and MS experts said the $23,000-a-year drug may return to the market after more testing. Researchers must monitor patients who took the medicine for at least a year to see whether PML crops up in more people, said Howard Weiner, a neurologist at Harvard Medical School and Brigham and Women's Hospital in Boston.

``We have to find out how prevalent this is,'' said Weiner, who directs an MS clinic visited by about 5,000 patients each year. ``One has to understand all the variables and the scientific basis for what happened to make a decision.''

Elan and Biogen were to discuss Tysabri with FDA officials today. ``We don't expect to report on our internal meetings with companies,'' said FDA spokeswoman Lenore Gelb, who declined to comment further.

MS is a neurological disorder that robs people of muscle coordination and balance, sometimes leading to damaged vision and paralysis. PML, caused by a common virus that most people's immune system keeps in check, strips away the myelin sheath that protects the nerves in the brain, eroding mental function, vision, speech and muscle coordination and leading to paralysis, coma and death.

MS Society

Tysabri, which cut the number of MS attacks by two-thirds in clinical
trials, may be sold again with additional warnings on the label guiding doctors how to use the drug, said Anita Kawatra, a spokeswoman for Elan in New York. There haven't been any reported PML cases in patients taking only Tysabri or only Avonex, the company said.

Some patients said they would still take Tysabri if it is shown to be safe, noting that the complications have occurred only in combination with Avonex. Researchers and company officials hoped the drugs would be more effective when given together because they use different ways of controlling MS.

``There are a lot of drugs out there that can be lethal in combination,'' said John Harrison, an attorney at Cleary Gottlieb Steen & Hamilton LLP in New York, who was diagnosed with MS a year ago, in a telephone interview today.

``The last thing I'd like to see if is the FDA suddenly puts things on a slower track.''

Faster Approval Questioned

The second PML case doesn't change the National Multiple Sclerosis
Society's position in support of a full evaluation of the data, said Patricia
O'Looney, director of biomedical research programs for the New York-based advocacy group. The society supported the FDA's approval of Tysabri based on data from the first year of a two-year study.

``We hope that the drug is put back on the market if it's found not to be associated with PML,'' O'Looney said in a telephone interview.

Wayne State's Kahn said the PML cases suggest the FDA's accelerated
approvals, typically applied for conditions including cancer, AIDS and
Alzheimer's disease, may not always be appropriate for less serious conditions. The drug isn't approved in Europe.

Tysabri represents a new class of medicines for which ``we don't have any precedent,'' Kahn said.
``Why not err on the side of safety?'' Kahn said. The FDA's normal
procedure would have been to wait for the full two years of data. ``Had that been the approach, this drug would not have been approved.''

--With reporting by Carey Sargent in London. Editors: Rohner, Simison

Story illustration: To see a series of screens of information on
Elan, see: {ELN ID <EQUITY> CNP03324630106 <GO>}. To see
today's top health-care stories, see: {HTOP <GO>}.

To contact the reporters on this story:
John Lauerman in Boston at (1) (617) 338-5812 or
jlauerman@bloomberg.net.
Michelle Fay Cortez in Minneapolis at (1) (763) 416-0609 or
mcortez@bloomberg.net.

To contact the editor responsible for this story:
Robert Simison at (1) (202) 624-1812 or rsimison@bloomberg.net.

[Arron]

with all due respect to Mr. Khan, I believe he makes some extreme and unfounded statements in this article.

``If there is an association, I think this drug is history,'' Kahn said in an interview today. ``PML can't be a black-box warning disease when it is invariably fatal.''

Mr. Khan should be aware that the FDA issued black-box warnings on antidepressants prescribed to children and teens, indicating that the drugs can increase suicidal tendencies in children and adolescents. Not to be glib, but suicide attempts also have a high likelihood of fatality or grave injury.

Elidel and Protopic, both for eczema, carry a black box warning for cancer and serious infection. Again, cancer has a strong possibility for fatality and the drugs are still on the market.

Bextra has a black box warning for horrendous skin/eye/mouth blistering and infection, sometimes leading to death. "The black box warning that was added details serious skin reactions (ie. toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme) reported in patients receiving Bextra. Some of these reactions have resulted in death. " (http://www.empireblue.com/physician/web ... tra2.shtml)

So no, the incidence of PML does not automatically mean Tysabri is "history."

The next rather aggressive Khan statement is:

The FDA's normal procedure would have been to wait for the full two years of data. ``Had that been the approach, this drug would not have been approved.''

This information came out after the two year data was complete, though certainly not by a long margin. Even if the information was available prior to the approval process, as we've seen in the numerous fascinating articles posted here today, the FDA's opinion on suspending Tysabri is far from clear. To say that the FDA would certainly not have approved Tysabri is acting in the role of an omniscient, but with very little data to back that up.

Excuse the tirade, but just had to speak up at irresponsible statements coming from an authoritarian figure.

[OddDuck]

Well, I think we will have to agree to disagree, Arron.

The examples you give are all things that are not "invariably" fatal. All of which you mention can be treated. PML cannot.

And I believe that what Dr. Khan is simply saying is that if the FDA had waited until after the two years as is normal procedure, these deaths would have happened (which they did happen), which would have prevented the FDA from approving the drug in the first place. Arron, that is true. These deaths happened three months after approval. If they had waited another year, these deaths would have happened BEFORE the drug had been approved, and they would not have approved it.

That's not saying they would NEVER have approved it, they just wouldn't have approved it NOW, hence all of this fiasco of pulling it back off, getting some people worried and/or upset, etc.

I don't see the complication in those statements at all. Besides, Dr. Khan says "I think". That's his opinion. Why should it upset anyone?

Sometimes I wonder if people don't put way too much "power" in people's words and opinions. "Authoritarian figure"? Dr. Khan is just a person expressing his views, that's it.

Deb

[Arron]

Hi Deb,

It seems PML is not always fatal. Besides 10% spontaneous remission, the latest (unsubstantiated) update on patient #2 is that he is (at least temporarily) recovering/stabilizing. Maybe this merely prolongs the inevitable, but as with everything Tysabri-related these days, questions remain.

Maybe I'm missing some built-in administrative delay or my timelines are off, but if the FDA was willing to fasttrack approval in the first place, why are you convinced they would have waited at least 3 months after the 2 year data was complete to approve the drug?

And yes he says "I think" to refer to the drug "being history" (an insensitive and inflammatory-- no pun intended-- phrasing for those people hoping for Tysabri to be re-introduced), but he says that FDA approval was a sure no-go as if he knows that for fact, when as of today we are not even certain if the FDA agreed with Biogen/Elan to suspend Tysabri.

And yes, I do believe that someone selectively quoted as a lead researcher and director of an MS clinic, and in an article from a highly respected news organization, is in a position of responsibility and authority. There is simply too much uncertainty right now from every single step of the ladder for anyone to be making either absolute or flippant statements at this point. We are all back to the proverbial drawing board until these two companies ascertain more data from their data pool.

Anyways, let's hope for a substantial week of news + miracle recovery for patient #2.

[OddDuck]

Anyways, let's hope for a substantial week of news + miracle recovery for patient #2.

Absolutely! And that's really the bottom line for me. My best and heartfelt wishes goes out to both the patient and his/her family.

Deb

[radnaim]

Hi!

A do totally agree with Arron that he tries to balance the Tysabri forums against two very hardworking forum writers with 800 posts who always say the same irrespective from what information is available.

Regarding the PML - I would not be surprised if the PML caused by Tysabri would not turn out to be fatal. As far as I can figure out, PML is caused by immune suppression. In case of AIDS, if the immune system can be revitalized with antiretroviral drugs, PML subsides. In case of Tysabri, if the treatment is stopped, the immunesuppression can be stopped entirely.

If somebody rereads the statement on the death of the first patient, he was treated with Tysabri and Avonex - and even immunesuppressing steroids! - after he had his first symptoms - because he was misdiagnosed to have an MS flareup. Now, that doctors know that this is caused by the virus, I think the best thing to do is to stop all treatments - and the patient will be cured.

I think some tests can be developed to check for JC virus activity that will be obligatory for Tysabri patients similar to liver function tests.

I think slowly we can see the light on the end of the tunnel and this drug will be back soon.

[flora68]

.........It seems PML is not always fatal. Besides 10% spontaneous remission, .....

I'm confused about this statistic, Aaron. Are you sure it means permanent remission of PML, or just temporary?

The latest, most aggressive highly active anti-retroviral therapies (HAARTs) are helping some AIDS patients with early PML to live longer, up to three or four years, but no source I can find talks about people having permanent remission unless the PML was caused by immune-suppression, as in organ transplant patients. And they got better upon discontinuation of the corticosteroids.

Maybe the rest of the Tysabri patients are (or will very soon be) out of any danger if PML now that the Tysabri has been discontinued. (That's just my thought, totally unsubstantiated by anything real .)

.....Bextra has a black box warning for horrendous skin/eye/mouth blistering and infection, sometimes leading to death. "The black box warning that was added details serious skin reactions (ie. toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme) reported in patients receiving Bextra. Some of these reactions have resulted in death. ...

Aaron, I get your point, and I don't mean to nit-pick, but I think you picked the wrong product's risks to compare to Tysabri's.

The problem with Bextra, as I understand it, is that the makers failed to include a specific warning for those who are allergic to sulfa, informing them that they could be vulnerable to the problems you mentioned above.

They've also added a contraindication for patients who are status pre-or post-op, especially post-CABG or other heart surgery.

But the Bextra reactions you mentioned aren't nearly as deadly as PML, unless the patient keeps taking the Bextra after the skin symptoms have begun and doesn't seek treatment; my doc warned me about that specifically when she put me on Bextra, as did my pharmacist.

They both told me that although I've never had a problem with sulfa or any other antibiotics, if I notice the beginning of any skin or mucosal eruptions or symptoms, to discontinue the Bextra right away and call the doc. They, and the prescribing info at the time, also indicated that the reactions usually go away when the medication is discontinued.

The same company did put the warning for sulfa-allergic patients on their other CoxII drug, Celebrex, from the very beginning.

[HarryZ]

Arron,

Maybe I'm missing some built-in administrative delay or my timelines are off, but if the FDA was willing to fast track approval in the first place, why are you convinced they would have waited at least 3 months after the 2 year data was complete to approve the drug?

Let me try and explain some time-lines here as to what may have happened had the FDA not fast-tracked the Tysabri approval last November.

If Biogen had waited until all of the Phase III 2 year trials were completed, the tabulation of this data, at the earliest, would have been available for submission sometime in early March. The FDA would have reviewed this data and the approval would have taken until sometime late this year before a decision would have been given. If you check back when the Phase III trials started, this approximate time line was made public.

The PML cases, according to Biogen, were made aware to them around Feb. 18 this year. At this point, the two year data was still not completely done so the PML cases information would now have become part of the approval consideration process. I can assure you that a whole new outlook on Tysabri would have taken place and Biogen would have had to provide tons of data to the FDA about these cases. And they don't have this data and it is likely going to take a lot of time and effort to provide it. So in all likelihood, Tysabri's approval would have been severely delayed at best but at least the current recall situation would have been avoided.

Certainly not official by any means and of course their opinions only, but some MS docs are quietly stating that Tysabri may never see the light of day again. Whether this comes to be true is anybody's guess right now.


Harry