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TYSABRI(R) Demonstrates Sustained Improvement in Functional Outcomes in Multiple Sclerosis Patients According to New Post-Hoc Analysis

Biogen Idec (NASDAQ: BIIB) and Elan Corporation, plc (NYSE: ELN) announced that a post-hoc analysis showed TYSABRI®(natalizumab) treatment increases the probability of achieving sustained improvement in physical disability over two years when compared to placebo. This post-hoc analysis provides the first evidence that TYSABRI is associated with a significant improvement in functional outcome, rather than only slowing or preventing progression of disability, in those living with relapsing multiple sclerosis (MS). These findings were derived from a subset analysis of the Phase III AFFIRM trial and were presented today as a poster presentation at the World Congress on Treatment and Research in Multiple Sclerosis in Montreal, Canada. This is the first joint meeting of the Americas Committee on Treatment and Research in Multiple Sclerosis (ACTRIMS) and its counterparts in Europe and Latin America: ECTRIMS and LACTRIMS.

"These results show that TYSABRI treated patients are significantly more likely to experience a sustained improvement in disability compared to placebo patients. This finding from a post-hoc analysis of the pivotal AFFIRM trial supports both the earlier findings from the AFFIRM trial that TYSABRI is associated with an improvement in quality of life as well as anecdotal evidence of recovery of function in some patients.” said Frederick E. Munschauer, MD, Smith Professor and Chair, Department of Neurology, State University of New York at Buffalo. "While, like TYSABRI, other therapies have shown a slowing of progression in disability, this analysis represents the first evidence supporting a sustained improvement in function associated with an approved disease modifying therapy.”

Post-hoc Disability Analysis of Phase III AFFIRM Study

The proportion of patients exhibiting sustained improvements in physical disability in the AFFIRM study was determined based upon the Expanded Disability Status Scale (EDSS) over two years in patients with relapsing MS. EDSS is one of the oldest and most widely utilized methods of quantifying disability in MS.

Post-hoc analysis of AFFIRM patients assessed sustained improvement in disability among patients with a baseline EDSS score = 2.0. Improvement in disability was defined as a one-point decrease in EDSS score sustained for 12 weeks. The cumulative probabilities of 12-week sustained improvement in disability at two years were estimated using the Kaplan-Meier method. Treatment effects were analyzed using the Cox proportional hazards model adjusted for baseline EDSS score. The distribution of sustained improvement by baseline EDSS score for each treatment group was also examined.

TYSABRI produced significant results on the cumulative probability of sustained improvement in disability in those treated over two years compared with placebo. In patients with a baseline EDSS score = 2.0, the probability of achieving sustained improvement was 29.6% with TYSABRI (n=417) compared with 18.7% with placebo (n=203) (p=0.006). In patients with an EDSS score = 2.0 and highly active disease at baseline, the difference between groups was even greater, 35.5% for TYSABRI (n=103) and 15.4% for placebo (n=40) (p=0.045).

The submitted abstract for this study, entitled "Natalizumab significantly increases the cumulative probability of sustained improvement in physical disability” (ID #P474), is available on the World Congress’ website.

Cheers Lauren. My wife (diagnosed MS last year) and I are visiting our neuro next week to discuss her recommendation of Tysabri so it was great to hear this.

Down in NZ we have to pay for treatment unless edss 4 or greater so nice to know its this effective. (Only 3 people in NZ on it because of cost).

I've been researching the drug options and my personal opinion to my wife was that if it were me, Tysabri would be my option. We then got a call from our neuro saying Tysabri just restarting and if we could pay it would be her choice for my wife. So stars seem to be aligning!

As much as we'd all like to think so, New Zealand is not Australia's seventh state

New Zealand is a fully fledged sovereign nation, though it appears with a less generous government pharmaceutical scheme. I'm not aware that the Australian PBS requires a specific EDSS prior to Tysabri treatment.

Of course, we Aussies have had to wait for Tysabri to be made available (though given the history, perhaps not such a bad thing), but now that it is available, everybody in the country (regarless of age, income or employment status) can access the drug for $32 per month. That's socialised health care for you (as opposed to socialised investment banking!!!).

Sort of like Canada being part of the USA I guess haha...Yes NZ situation is not great and I know of two people who returned to either Australia or Denmark so they could access subsidised treatment for their MS. We do have lots of sheep though

To mjs: you said,

we Aussies have had to wait for Tysabri to be made available (though given the history, perhaps not such a bad thing), but now that it is available, everybody in the country (regarless of age, income or employment status) can access the drug for $32 per month

How wonderful!

Thank you so much for the info regarding the PBS/Australia's differences from New Zealand's.

Take care now, Lauren

dreddk wrote:TYSABRI(R) Demonstrates Sustained Improvement in Functional Outcomes in Multiple Sclerosis Patients According to New Post-Hoc Analysis

Never one to trust what Biogen says about any of their products, I sent this press release to a friend who has the ability to look beyond what appears on the surface when it comes to clinical trials on MS.

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First of all Post Hoc means after the fact which I find to be very suspicious given that if these results were truly significant then why didn't Biogen mention them in the original study results?

The AFFIRM trial is completed and it was a 2-year study so why did Biogen do their post hoc analysis of sustained improvement for 12-weeks? Why not tell the actual sustained improvement for 2 years rather than tell the probability from cumulative 12-week data?

They only included patients with an EDSS score of 2.0 at baseline. A patient with an EDSS score of 2.0 is very early on in the disease and it is typical for the patient to have spontaneous remissions that may last for several months at such an early stage of the disease and to not see much increase in disability for several years. (An EDSS score of 1.5 is no disability and a 2.0 score is minimal disability in one function system.) Biogen are claiming that Tysabri increases the probability of achieving sustained improvement in physical disability over two years when in fact they only included people who had an EDSS score of 2.0 that really have no physical disability to start with.

The Tysabri group had more than twice as many people in it than did the placebo group. Tysabri group was 417 and the placebo group was 203. Remember in statistics you can increase the power of the study meaning you can increase the effect by increasing the number of subjects. The placebo group showed 18.7% sustained improvement and the Tysabri group showed 29.6%. Given that the Tysabri group was twice the size of the placebo group, the percentage of effect should have been greater than twice the placebo effect to demonstrate even a little more effect than the placebo. Thus the results point to the probability that if the placebo group had been as large as the Tysabri group, the placebo group would have had as good or better effect than the Tysabri group in improving physical disability.

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Statistics in trials and all the analysis that follows is beyond my understanding of this complicated process and that is why I ask others for their comments in this area since they are far more knowledgeable than I ever hope to be with this.

Biogen's expected sales for Tysabri is FAR below what they planned in their initial marketing. So it isn't surprising that they are "dredging" data from the Affirm trial to try and increase their sales. Biogen has one of the slickest marketing departments going!

Harry

Hi Harry,

I share your suspicion about the "new" figures from biogen...
(In the german biogen´s forum "ms-life.de" they even refused to comment on the new pml-cases - and so on....)

But I just don´t get you here:

HarryZ wrote: Given that the Tysabri group was twice the size of the placebo group, the percentage of effect should have been greater than twice the placebo effect to demonstrate even a little more effect than the placebo. Thus the results point to the probability that if the placebo group had been as large as the Tysabri group, the placebo group would have had as good or better effect than the Tysabri group in improving physical disability.

Harry

I´m also not very good at statistics but that sounds strange to me..
Could you explain?

Biogen are claiming that Tysabri increases the probability of achieving sustained improvement in physical disability over two years when in fact they only included people who had an EDSS score of 2.0 that really have no physical disability to start with.

My feeling is that unless a person is actually suffering from the symptoms that MS can bring, one can never really fully comprehend what significant hope this news brings to some MS patients. And I am not referring to a person that had/has a loved one with MS.

Avonex, Betaseron, Rebif, & Copaxone have never been able to make this claim of "Showing BOTH Significant Slowing in Disability Progression and Sustained Improvement in Physical Disability"..., it is easy for others to dismiss proven data and statistics if their mindset continues to remain negative.

None of the older generation MS medications (the ABCRs) have ever made these dual claims and MS patients never reported any kind of "anecdotal" evidence of improvements in their symptoms while being on them, basically only reporting their awful side effects & injection site reactions (not to mention patient noncompliance with the older generation therapies).

And that is all I have to say on this subject.

Lauren

Hi Ursula,

HarryZ wrote: Given that the Tysabri group was twice the size of the placebo group, the percentage of effect should have been greater than twice the placebo effect to demonstrate even a little more effect than the placebo. Thus the results point to the probability that if the placebo group had been as large as the Tysabri group, the placebo group would have had as good or better effect than the Tysabri group in improving physical disability.

Harry

I´m also not very good at statistics but that sounds strange to me..
Could you explain?

You don't expect me to try and figure that out, do you?

However, I did ask for clarification from my source and this is what I received...
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.......The percentage tells you the amount of change seen, but the power tells you how dependable the results are and that they are not just by chance. You can increase the power of a study by increasing the size of the study. The percentage of change may stay the same with the larger study but given that there was only a difference of 11% with a Tysabri group twice as large as the placebo group, it is unlikely that they would have reached significance with a smaller Tysabri group. Remember the size of the groups is determined by the anticipated effect of the drug. The greater the effect of the drug the smaller the number of subjects you need....

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What we have seen from Biogen here is some fancy statistical dredging in an attempt to promote the sale of Tysabri. This is what marketing departments of big pharma do....promote their drugs to increase sales and profit. This data was available two years ago from the Affirm trial yet Biogen is only now telling us about it??!! Like I said earlier, their anticipated sales are way below forecast and they need to stimulate more interest in the medication.

But please don't equate my suspicions about Biogen with the hope that any patient who decides to try Tysabri, gets some kind of benefit from it. Another reader has suggested that since I have never had MS myself, I don't appreciate what benefits Tysabri may give a person. My wife had MS for 36 years and prior to that my uncle had it for 25 years. I have seen what devastation this lousy disease can inflict. At the same time, I have followed the development and marketing of all the currently approved MS drugs (others as well) and have seen how the companies who make them can twist information to make it sound very good.

Unlike the CRAB drugs, Tysabri has basically been tested and used on patients who have mild cases of MS. It is far easier to get an IV once every 28 days than to inject one's self as often as the CRAB drugs require. That in itself brings a level of comfort to MS patients that never existed with the CRABs. The often nasty side effects of the CRABs are also not missed. Again, more cause for excitement and better feeling.

But don't get mislead by some of the Tysabri cheerleaders on the internet or by Biogen who likes to tell MS patients that this drug is the ANSWER to MS. It hasn't been around long enough and used by very large numbers of patients to determine how good or bad it may be. So far I have read that some patients do very well on it, others notice no change at all and some end up become sicker and have to stop using the drug. Sound familiar with MS medications? And again, the data that is used is from mild MS patients.

I really hope that in the long run, Tysabri provides a much better result to MS patients than the CRABs ever did because those drugs never did much for them. I also wish that the range of $3000-10,000 per Tysabri infusion was a lot lower. That kind of cost can bankrupt health care costs!

Harry