Campath Phase II results

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Campath Phase II results

Postby bromley » Wed May 02, 2007 7:16 am

Here are the Phase II Campath results.

http://www.genzyme.com/corp/investors/G ... 050207.asp

I think they are impressive for those with RR MS (I'm biased because I've seen excellent results following my first infusion last November). And the impressive reduction in relapses is when compared with Rebif.

These sorts of treatments are riskier than the CRAB drugs, but the risks identified to date can be monitored and treated. And you don't see the following results from the CRAB drugs:

Patients in both alemtuzumab arms also achieved a statistically significant reduction in disability compared with their pre-treatment baseline, as measured by their Extended Disability Status Scale (EDSS) scores.


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Postby Lyon » Wed May 02, 2007 12:05 pm

Thanks for the information Ian.
Dr. Coles’ presentation showed patients taking alemtuzumab at the high dose experienced an 87 percent reduction in the risk for relapse (p<0.0001) and a 66 percent reduction in the risk for progression of clinically significant disability (p<0.0098) when compared to patients treated with Rebif. At the low dose, patients taking alemtuzumab experienced similar results, with a 72 percent reduction in the risk for relapse (p<0.0001) and an 88 percent reduction in the risk for progression of clinically significant disability (p<0.0008) compared with patients treated with Rebif.
Heck, progression of disability is the main concern....I'd go with the low dose!

I'm probably an ingrate but I actually expected the numbers to be a little more favorable?

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Postby CureOrBust » Thu May 03, 2007 3:23 am

probably?

At first I must admit I was a little underimpressed with the results, but the thing to remember is that this is as compared to another drug, not placeebo.
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Postby Lyon » Thu May 03, 2007 5:19 am

CureOrBust wrote: At first I must admit I was a little underimpressed with the results, but the thing to remember is that this is as compared to another drug, not placeebo.
Hi Cure,
I wish I were a little better with math and statistics because I've never fully understood what that means.

So with the crabs being (supposedly) about 30% that means Campath would be close to 100% ??

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Postby gkalman » Fri May 04, 2007 4:38 pm

Don't we all wish it worked that way.

If there are two effects, first reducing a rate by 30% and the other by 80% on top of the first, the effect is multiplicative.

I.e., after the first, the rate is at 70% of where it would have been before, and after the second, at 14% (.7*.2). Thus, the overall reduction would be 86%.
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Postby Lyon » Fri May 04, 2007 4:43 pm

gkalman wrote:Don't we all wish it worked that way.

If there are two effects, first reducing a rate by 30% and the other by 80% on top of the first, the effect is multiplicative.

I.e., after the first, the rate is at 70% of where it would have been before, and after the second, at 14% (.7*.2). Thus, the overall reduction would be 86%.
Hi Gary,
Yup, I knew I wouldn't understand it so thanks for including the final tally!

Jeez, 86% doesn't sound too bad!

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Postby bromley » Sat May 05, 2007 1:30 am

Thanks gkalman,

I tried to come up with an understandable interpretation using some illustrative numbers - but it got too complicated. It's complicated because: (a) the two doses of Campath used in the trial (b) the fact that the trial period covered two years (c) the comparison with Rebif (d) that the dosing of Campath was stopped during the trial.

Professor Compston from Cambridge said at a presentation last September that Campath reduced relapses by c.95%. Given that it wipes out your T and B cell for a while - the c.95% looks feasible.

I'm in Cambridge later this month for my check-up and will ask about the numbers.

As one case study - I had three relapses in 2006 (Jan / June / October (bad one)) - and was on Rebif since Feb 2006 until start of November 2006. I had my five day infusion at the end of November and, so far (six months in), not a whisper of a relapse and a really impressive recovery of deficits.

This drug won't be for everyone (it comes with higher risks) but at least for someone with very active RRMS, it's an option if the CRABs aren't having much effect. The longer impact of this drug on the disease is unknown but the researchers at Cambridge are learning a lot more about (a) the immune system response (b) repair.

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Postby finn » Sat May 05, 2007 2:42 am

gkalman wrote:If there are two effects, first reducing a rate by 30% and the other by 80% on top of the first, the effect is multiplicative.

I.e., after the first, the rate is at 70% of where it would have been before, and after the second, at 14% (.7*.2). Thus, the overall reduction would be 86%.

We're talking about relative change here, not multicaptive effect.

We know that the more effective dose of Campath reduced relapses 87% more than Rebif. Thus, if Rebif reduced relapses by 30%, Campath would have reduced them by 56,1%. The relative difference between 56,1% and 30% is 87% ((56,1-30)/30x100=87).

Unfortunately we just can't calculate the absolute effect of Campath in the study as long as we don't know how effective Rebif was.

Be well.

-finn
"The great tragedy of science - the slaying of a beautiful hypothesis by an ugly fact.” -Thomas Henry Huxley
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Postby CureOrBust » Sat May 05, 2007 6:48 am

finn wrote:Thus, if Rebif reduced relapses by 30%, Campath would have reduced them by 56,1%. The relative difference between 56,1% and 30% is 87% ((56,1-30)/30x100=87).
I dont agree with your numbers finn, and Rebif has a generally accepted (ie derived from previous large studies) effectiveness of around 30% (i think for relapses, not for disability progression, but thats another misalignment in all our calcs). However, assuming 30% is right. And there were no anomolies such as there actually were with people coming off of treatments etc etc etc The simple maths in my eyes is:

Rebif is 100%-30% = 70% Not effective.
Campath is 88% more effective (from the results), so Campath would be:
70 % * (100 - 88)/100 = 8.4% ineffective
Therefore, 100-8.4 = 91.6% effective by my math, which also sorta aggrees with what Ian has been told ie around 95%.

The trick to remember in the maths is that Campath is working on the numbers that Rebif failed on (ie the 70% and not the 30%)

Or, by example, if we have 200 people in the study (100 on each treatment), 70 people on rebif would of "failed" while only 8.4 people on Campath would of "failed". Giving the final figure of 88% via, 100 - (8.4 / 70) = 88% where we are comparing the numbers of those that failed (ie 8.4 to 70)

NB: I know there are a LOT of assumptions, simplifications and crossing of numbers in the above.
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Postby bromley » Sat May 05, 2007 7:07 am

Cure, Thanks - we might be 12,000 miles apart but we think the same.

Finn - I'm assuming your stats lecturer was a certain Professor Z :)


All of this will become clearer when the data are published with the research paper about this trial.

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Postby finn » Sat May 05, 2007 7:36 am

CureOrBust wrote:I dont agree with your numbers finn, and Rebif has a generally accepted (ie derived from previous large studies) effectiveness of around 30% (i think for relapses, not for disability progression, but thats another misalignment in all our calcs). However, assuming 30% is right.
COB, thanks for your comment. We seem to disagree with the numbers. I'm sorry, but I'm not going to change my opinion. I'd still say that they are talking about relative* difference between treatment groups, and if Rebif reduced relapses by 30% campath would have done it by 56%.

But I do agree with you on one thing. We don't know the absolute* numbers so these calculations are all based on speculation.

bromley wrote:Finn - I'm assuming your stats lecturer was a certain Professor Z :)
Thanks Ian, but I'm trying to think with my own brain ;-)

Be well.

-finn

*The difference between absolute and relative way to tell the difference between two groups is well explained in this Accelerated Cure's newsletter: "If 20% of the placebo group had relapses and only 10% of the active drug group did, then there was a 50% reduction in relapses for the drug compared to placebo (that’s relative) but only a 10% reduction overall (absolute)."
"The great tragedy of science - the slaying of a beautiful hypothesis by an ugly fact.” -Thomas Henry Huxley
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Postby Lyon » Sat May 05, 2007 7:54 am

finn wrote: "If 20% of the placebo group had relapses and only 10% of the active drug group did, then there was a 50% reduction in relapses for the drug compared to placebo (that’s relative) but only a 10% reduction overall (absolute)."
Thanks finn,
At least for me, that makes the whole thing a lot more understandable.
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Postby bromley » Sat May 05, 2007 9:32 am

Finn,

You wrote:

We know that the more effective dose of Campath reduced relapses 87% more than Rebif. Thus, if Rebif reduced relapses by 30%, Campath would have reduced them by 56,1%.


We could argue forever about the stats. Remember - statistics are like a hostage, you can torture them and get them to say anything.

I'm pretty confident that Campath reduces relapses by more than 56.1%. Professor Compston who heads up the Campath teams uses 95% in presentations. Out of interest I just received an e-mail from a neuro who was at the AAN conference (he is not connected to the Campath team). I had asked him about the Rituximab results. His response:

The Rituximab results were interesting and in keeping with expectations, but nothing like the Campath results which blew everything away.


I can't believe he would be so impressed with a treatment which only reduces relapses by 56%.

I await the publication of the data.

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Postby Lyon » Sat May 05, 2007 6:13 pm

For me, this about says it all
Safety Results
In the comparison of safety parameters of alemtuzumab vs. Rebif, a greater number of serious adverse events (a subset of total adverse events) were reported in patients receiving Rebif than in the two alemtuzumab dose groups combined. Most of these were associated with patients who were hospitalized for treatment of their MS.
From what I've seen, being diagnosed with MS is a little like finding yourself hanging by your fingertips on a cable suspended over a great chasm.

That scenario seems to leave a person with only two options:

Option one is to stay put and hang on for deal life in hopes of holding off the inevitable as long as possible. At most, the use of the "recommended treatments" might be akin to taking vitamins in hopes that your fingers will grip the cable a little longer.

Option two is attempting to move hand over hand to the edge of the chasm with hopes of saving yourself. Sure, that might seem risky because it will cause your arm to tire more quickly, possibly before you make it to safety.

For some reason in the topsy turvy world of MS the perception has gotten twisted so that the "safe" thing to do is to stay put and wait for the inevitable and the "risky" thing is attempting to save yourself.

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Postby finn » Sat May 05, 2007 11:44 pm

Ian,

I agree with you in this one:

bromley wrote:We could argue forever about the stats. Remember - statistics are like a hostage, you can torture them and get them to say anything.
Yes. Actually, we have a saying here; "lie, mother of all lies, statistics". For once I'd like to see data from MS-drug trial presented only "raw", without any statistical interpretation. It would be nice to know the total amount of clinical and pathological events (relapses, lesions, changes in EDSS, etc) in all treatment groups before and after treatment, and also learn about the way the information was collected and interpreted (for example, how long it took before a relapse turned into a permanent change in disability). It might be possible to find all that information in some of the full articles to be published, but not usually in abstracts and never in drug company press releases.

bromley wrote:I can't believe he would be so impressed with a treatment which only reduces relapses by 56%.
I'm sure he wouldn't. That is why evaluating raw data instead of statistical interpretations would be better. But who knows, maybe he has been able to do it, and my calculations are fundamentally wrong. After all, I couldn't know how well Rebif worked in the study, and how the comparison between treatment groups was really done to get the numbers presented in the article.

bromley wrote:I await the publication of the data.
Me too.

Be well.

-finn
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