This Is MS Multiple Sclerosis Community: Knowledge & Support

Woohoo!!!


FDA Grants Accelerated Approval of TYSABRI, Formerly ANTEGREN, For the Treatment of Multiple Sclerosis

Biogen Idec (NASDAQ: BIIB) and Elan Corporation, plc (NYSE: ELN) announced today that the U.S. Food and Drug Administration (FDA) has approved TYSABRI(R) (natalizumab), formerly referred to as ANTEGREN(R), as treatment for relapsing forms of multiple sclerosis (MS) to reduce the frequency of clinical relapses. FDA granted Accelerated Approval for TYSABRI following Priority Review based on one-year data from two Phase III studies, the AFFIRM monotherapy trial and the SENTINEL add-on trial with AVONEX(R)(Interferon beta-1a).

TYSABRI, the first humanized monoclonal antibody approved for the treatment of MS, inhibits adhesion molecules on the surface of immune cells. Research suggests TYSABRI works by preventing immune cells from migrating from the bloodstream into the brain where they can cause inflammation and potentially damage nerve fibers and their insulation.

"TYSABRI is a powerful and innovative therapy that offers new hope for hundreds of thousands of people living with MS," said James C. Mullen, chief executive officer, Biogen Idec. "We believe TYSABRI will revolutionize the treatment of MS and become the leading choice for patients and physicians."

"TYSABRI is a significant breakthrough for patients with MS," said Kelly Martin, president and chief executive officer, Elan. "The approval of TYSABRI, with its unique mechanism of action and new level of efficacy, has the potential to make a genuine difference in the lives of patients and families who struggle with the debilitating effects of this disease."

<shortened url>

I saw on another site I check on. Is that this drug is going to cost $2500 a month. Now I have not found anything to confirm this. This info was posted by someone in one of the trials.
So please don't quote me.

I can already see the likes of Serono, Teva and Burlex circling the wagons and planning their marketing strategies to ensure they keep their slice of the pie in the MS world of medicine.

You can bet these companies will examine every period and comma in the clincial trials of Tysabri when they become available.

Harry

Label:
http://www.tysabri.com/downloads/produc ... mation.pdf

Harry,



You're right:

http://uk.biz.yahoo.com/041124/323/f79at.html

Deb

Would you like fries with that?



<shortened url>

PS Anyone know what the status of this drug is in the UK? Does NICE have a position already?

_________________
John
I am what I am

Part of the trial info released contained this statement:

"The exact relationship between MRI findings and the clinical status of patients is unknown. Changes in lesion area often do not correlate with changes in disability progression"

Now this really gives me a lot of assurance that Biogen has done all their homework on this drug!!

Harry

It's interesting to note that the above text is almost identical to the language that Biogen uses to describe the MRI results with Avonex.

"The exact relationship between MRI findings and the clinical status of
patients is unknown. The prognostic significance of MRI findings in these
studies has not been evaluated."

This statement does not lessen the efficacy of Avonex, it only indicates that Biogen's study was not designed to specifically answer questions regarding MRI results and disability progression. It's likely that the studies of antegren did not directly address them either.

NHE

it's a standard disclaimer because the correlation between MRI lesions and disability is poor. for example, from serono's lit on rebif:

"(1) The exact relationship between MRI findings and clinical outcomes for patients is unknown."

I knew there was a reason why I don't place much credence in the CRAB drugs and now Tysabri. ..I guess we can now call all of them the CRABTRI drugs !

All of their studies post the results of a reduction of lesions over placebo but there isn't any correlation between the lesions and level of disability !!!! And they charge thousands of dollars a year for these drugs!

Harry

Harry, the reason there is a standard disclaimer is that the brain is too complex and no one can draw a straight, defensible line. But, relapse rate and new lesions seem to go hand in hand. That Tysabri patients saw 66% reduction in relapse rate v placebo (double the efficacy of the next best treatment - beta inteferons) is a good thing. That new lesions were reduced to virtually nil at the same time is amazing. Now we wait for 2 year data and EDSS scores. MS

PS - Did you see link to label from other thread? Very reassuring.

The one year data that they have taken that 66% rate from is already suspect!

I did see the table link on the site which is a brief description of the trial data. I forwarded this to a friend of mine who has done a lot of research in MS and knows how to read these studies. Here are the comments that I got back...............
___________________________________
First of all the patients who were in Study 1 had a disease duration of 5 years versus the patients in Study 2 had a disease duration of 7 years and consequently the percentage of relapse change is significantly different between the two Studies. Furthermore, the patients in Study 1 which Biogen has been boasting that it showed a 66% decrease in relapse rate, most likely had a very low score on the EDSS because "approximately 94% had never been treated with these agents (interferons or copaxone)" but of course they don't bother to tell us what the median EDSS score was in this group. They only tell us that patients were enrolled that had an EDSS score between 0 and 5.0. Most likely the majority of these patients were closer to 0 given that 94% had never received any treatment. (My comment: I believe that Serono alluded to this lack of information in their recent press release on Tysabri.)

Next if you look at the tables in Figure 1 you will see that under MRI Endpoints it says that the median number of new or newly enlarging T2 lesions was 0.0 for the Tysabri group in Study 1 meaning that no new lesions were formed. Well since no new lesions were formed then that means that 60% of patients put in the Tysabri group never had any lesions to start with because it states that 60% of patients in the Tysabri group in Study 1 had no lesions.

Now more tell-tale is the Gd-enhancing lesions (active lesions) because the median in both the Tysabri group and the placebo group in Study 1 were 0.0, meaning no change from before they entered the study. This shows that 96% of the Tysabri group in Study 1 had no active lesions, but the placebo group had only 68% with no active lesions prior to the study. The Tysabri group had only 3% with 1 active lesion prior to the study, yet the placebo group had 13% with 1 active lesion prior to the study. The Tysabri group had only 1% with 2 or more active lesions prior to the study and the placebo group had 19% with 2 or more active lesions before the start of the study.

Study 2 is just more of the same.

So do you see how the study was manipulated to show benefit according to their measurements of effect. Of course I wish people would pay more attention to the real issue here as they boldly state "The exact relationship between MRI findings and the clinical status of patients is unknown. Changes in lesion area often do not correlate with changes in disability progression." So what is the point in using this criteria to determine if a drug is going to have any effect on a MS patients life?!!

___________________________________________


I don't pretend to understand all the very complex data of a clinical trial but instead rely on people who do. I also received comment back from a member of the MS Consortium Group who specialize in MS treatment and research.....the individual told me that she and other members of this group are not very comfortable with the Tysabri data from Biogen.

Maybe the two year data from these trials will answer a number of quesitons that have gone unanswered so far. Maybe my and other people's major concerns about this drug will be laid to rest but until then and until a lot of people start to use Tysabri outside the clinical trial setting, I will be extremely cautious about Tysabri. I simply don't have a great deal of trust in pharmaceutical companies these days after what we have seen what happened with Merck(Vioxx) and Warner Lampbert. (Neurontin)

Harry

Harry,



If you are going to assume the worst then I guess that is exactly what you will see.

MS

MS,



I think you may be missing my point in all of this. I am not assuming the worst nor the best nor anything in between. What the person who read this abstract of the clinical trial was stating was that we simply don't know and the data that Biogen has released simply isn't giving the information that most researchers want to see. When that happens, a lot of red flags are raised.

This quote was taken from Dr. Ben Thrower, a member of the MS Consortium who was commenting on Tysabri's FDA approval.

(Dr. Ben Thrower, Medical Director at the MS Center at Shepherd.)"However, I am advising patients to be cautious because the available data is short-term," he added.

Now Dr. Thrower is a VERY well respected MS neurologist and he is expressing caution based on what he has seen about Tysabri. I don't think that we could say that he is "assuming the worst".

Again, my point in all of this is that we simply don't have enough data about Tysabri and neither does Biogen. And until they make available everything that exists or is coming, a scientific analysis of their trials can't be done.

Harry

Harry,

Am once again feeling a little touchy because you again made a comparison to Vioxx with no just cause. There is no evidence that Tysabri (Antegren) has significantly greater side effects than those associated with the IV itself. Please look at the label.

Now, could it have greater side effects? Never say never. But to make the comparison to Vioxx is, in my opinion, not at all fair.

And, in terms of efficacy, just look at the Sentinel trial. All patients were already very, very active with EDSS scores significantly above zero, and again the difference between Antegren with beta interferon and beta interferon along was extremely striking. The beta interferon was Avonex, which is the very same molecule as Rebif.

I don't object to caution, only the unfair comparisons and the desire to see only those possible questionable issues and to ignore the very compelling data.

If I were diagnosed with MS today, Tysabri would be my choice and if my physician would not prescribe it then I would find a new neurologist.

MS