This Is MS Multiple Sclerosis Knowledge & Support Community

Many of us Msers are already at 100% risk of further disability and disease progression. The CRABs are a dismal failure for many of us. And along comes a brand new drug that offers us some hope and the FDA has decided to engage a RISK averse policy with new drugs using this one as a test case?

The FDA really goofed when they halted and placed a moratorium on an almost flawless clinical study of a new drug in the Tysabri AFFIRM trial.

Some one at the FDA lost control and sight of the bigger picture in the scheme of all things related to legally mandated and tightly controlled drug discovery!

Who are these charlatans, prima donnas, and hacks who robbed the courageous AFFIRM trial MSers and us of OUR wonderful discovery?

I personally would love to hear what the Tysabri did for you. My husband, the MSer, and I are anxiously awaiting the return of Tysabri. His DR said in Oct that she was surprised that it wasn't out by now. She has a friend that took one dose and felt so much better, looked better, and etc. Gary, my hubby, hinges on drastic disabilities. He is just one attack away from disaster and we cringed living this way. Tysabri is hope for him. Copaxon has limited his attacks, but they still happen from time to time. Tysabri may not do a thing, but it is our hope that it will. At least buy him enough time until something comes along to "heal" present damage.

Yep, the new drug was selling like hotcakes right out of the chute. I also was in full support of the suspension of the drug from commercial distribution and the Sentinel clinical study when the safety issue came to light. However, I seriously want to know who put the kabash on the AFFIRM trial. Not only was it an ignorantly BIASED action against established clinical trial protocol, it was a gross error in regulatory judgement, an almost criminal injustice, and a horrible travesty in negligently delaying reasonable scientific discovery designed to hopefully benefit its volunteers or pioneers by CHOICE.

Human clinical trials are set up to legally protect the overall health and safety of its clinical participants during a mandated drug discovery process. In doing so one desires to minimize exposure to a larger uninformed population of patients or public at large. The larger a clinical trial population is, the more accurate and reliable the data is that is collected and extrapolated from the in vivo experiment. The Antegren trials were the largest human clinical study ever designed for a new drug of this class, the humanized MAB Alpha 4 integrin bonding molecule, natalizumab.


The data in the AFFIRM MS trial is most spectacular, not strictly because of its proven or shown clinical efficacy but, the side effect and safety profile exhibited in the trial is absolutely awesome for a novel drug of this kind. Remember that not all guardian Tcells are bound and blocked by the VCAM expressed from the available VLA4 repectors along the endothelial wall. The shorter-lived neutrophils are not blocked by the natilizumab SAM. A monotherapy infused patient is not totally defenseless against foreign invaders or any environmental exposure due to ingested or injected precursory agents.

Some tidbits to chew on:

The intrinsic invader, genetic defect, or disease mechanism of MS is already present if the patient is a properly diagnosed active MSer.

7 to 9% of all interferon treated MSers show presence of JCV proteins or antibodies present in the CNS or cerebrospinal fluid.

Interferon treatment naive MSers show almost ZERO presence of JCV proteins or antibodies in their CNS or cerebrospinal fluid. It is theorized that any present JCV cloaks itself and survives in the kidney tissue of an immunologically healthy human being. An MSer most likely has a defectively over-responsive or hyper active immune system.

Concomitant dosing of beta-interferon 1A was already known to reduce the active clearance of soluble VCAM in blood serum by 30% while boosting the VLA4 expression of the target Tcells concurrently with steadily increasing population of longer lived Tcells trapped from leaking thru the endothelial wall or naturally removed by decay or biological half life of the entire targeted Tcell population.

Don't forget the clinical data compiled and presented from the 2 year endpoint and safety review data from the AFFIRM trial met and exceeded the data presented from the one year endpoint in both SAFETY as well as never seen before efficacy for a gold standard, standalone indication of this fantastic novel therapy for MS!

Call me an idiot or crazy if you wish but, I already know I'm a slowly progressing veteran MSer and willingly able to make a well informed choice when Tysabri returns.

The drug will come back and I plan on being one of its first commercial recipients, once again.

Ciao and best wishes

Amelia,
I was lucky enough...and on top of my neuro enough..lol..to receive two Tysabri infusions. I felt better immediately and was feeling better and better as time went on. I quit falling (something that had left me bruised pretty bad the months before). I was able to get around with my cane instead of my walker....and the best...no fatigue! I got to spend the whole day with my 2 year old without having to go 'pass out'!
I quit taking all of my meds..and the spasticity was gone! No more baclofen or zanaflex! My family and friends could visually see me getting more mobile...and of course all of these improvements brought such hope and happiness! I cant wait to get my next dose!
Hang in there! There are many of us fighting for the speedy return of Tysabri.
Peace and Love,
Heather

Hi "Bull",

Don't forget the clinical data compiled and presented from the 2 year endpoint and safety review data from the AFFIRM trial met and exceeded the data presented from the one year endpoint in both SAFETY as well as never seen before efficacy for a gold standard, standalone indication of this fantastic novel therapy for MS!

A very knowledgeable participant on the Brain Talk MS Fourm jumped into the data from the Tysabri trials. This fellow had the ability to sift through information quite thoroughly and in the end, determined that Tysabri had about a 12% more effective efficacy rate than the CRABs. While better I don't think that could be classified as "fantastic".

Call me an idiot or crazy if you wish but, I already know I'm a slowly progressing veteran MSer and willingly able to make a well informed choice when Tysabri returns.

I think what is critical here are the words "well informed". Several MS docs have made the comment that they just aren't too sure about Tysabri and they want more safety information before they give it to their patients. Regardless of what a drug can do for a patient's illness, if it has the ability to become fatal to the patient, the docs want to know a lot of information about it first. And I don't think that Biogen/Elan have provided enough of this information yet.

At the same time, I understand the feeling of MS patients who will risk whatever danger Tysabri gives at the chance of becoming better. It's a horrible disease that slices its victims piece by piece. I only have to look at my wife who has fought MS for almost 35 years and see what it has done to her over this period.

Take care.

Harry

I intentionally quit Betaseron therapy in Oct 2004 in anticipation of starting Tysabri therapy as soon as it was commercially avialable after FDA approval.

When I received my first dose of Tysabri I had already been experiencing occasional MS relapses and disability progression from more recent exacerbations that began several months prior to receiving the new therapy. I had been on Betaseron therapy for almost 10 years. I had been recently experiencing horribly painful muscle spasiticity in my lower exteremities and abdominal muscles. I am also an RA/OA patient with documented arthritic disease and occasional pain in my joints, especially my surgically repaired knees. I have S.O.N. (severe optic neuritis) and am totally blind in my right eye. I am also hypothyrroid and suffer from heat intolerance and increased fatigue.

After I received my first infusion earlier this year I decided to do my own test on my joints and MS problems while on the Tysabri therapy. After over 10 years of mostly sedentary behaviour and persistant chronic fatigue from my MS, I overworked my body for several days following the first infusion. Not only had I not developed any pain or inflammation in my afflicted joints, I noticed that recent abdominal and lower extremity spasticity was slowly drifting away. At around week 6-8 after my second dose I had become much less irritable and less fatigued than I had ever had been in the previous ten years as an R/R MS patient. I was no longer having a difficult time sleeping at night and felt more rested than ever before after each nights rest. I also began walking for excercise again and took less power naps during the day.

Well, not to make a longer story short, after the drug was suspended I went on a long and difficult fact finding mission to find other MSers like myself who had experienced similar benefits in what I thought was really too good to be true. As of today, I have yet to find one MSer that isn't willing to DENY Tysabri as a possible eligible candidate for the best MS therapy they had discovered in their life long struggles with MS. I have met many MSers since February 28th. I have met 1-2-3 Tysabri dosed MSers. I have met one of the first MSers in the world to have pioneered the early dosing studies in the late 90's. I have met Sentinel patients. I have met an Affirm patient. I have also personally met, opined, and consulted with top FDA officials, medical researchers, neurologists, and immunologits. I have been to Capitol Hill to individually lobby for an expeditious FDA advisory review and thorough scientific evaluation of the risks and safety profile of this novel therapy for MS. But, most of all I have fighting the good fight in making sure our all our voices are heard in this critical and time sensitive issue. Concurrently all the previously FDA approved medicines and first generation therapies HAVE NOT been mitigating or suppressing the unrelenting advance of this nasty disease and its disability progression within the entire population of all diagnosed MSers of the world today.

Best wishes and please.............always seek the consultation and advice of licensed and experienced medical professionals before making a well informed decision about your own health and future quality of life.

Comparing the data and endpoints with other mutually exclusive clinical trials is unscientific methodology.


Please show me where any of the ABCR drugs showed 28% SUSTAINED disease reversal by 100% mitigated disease progression in any of the previous clinical trials or commercial patient population?


You can't because it may not exist exist. Simple case in point: How come so many of us MSers have continued to relapse, suffer exacerbation, and/or suffer further disability progression although many of us desperately continued our ABCR therapies? The ABCRs have been a classic case of continual expirimentation on the MSers at their expense financially and with added lessor quality of life as an entire patient population!

What is the overall safety profile of all the ABCR drugs in regards to the collateral damage incurred by these ineffective MS drugs relative to the actual damage caused exclusively by the disease itself within the entire MS population?


Good day

TheTysabriBull,
What about your ON? Did Tysabri do anything for it? My husband is totally blind in RE and legally blind in LE, both due to ON. Presently, we have found NO TREATMENTS other than the ABCR's, which are useless as far as disability progression is concered.

TheTysabriBull wrote:Comparing the data and endpoints with other mutually exclusive clinical trials is unscientific methodology.

I believe the poster (Mark) compared the data versus the placebo groups in each trial. I tried to find his message on Brain Talk but their site appears to be down this evening. I'll see if I can find it when the site is back up.

Please show me where any of the ABCR drugs showed 28% SUSTAINED disease reversal by 100% mitigated disease progression in any of the previous clinical trials or commercial patient population?

You don't have to convince me about the minimal efficacy of the CRABs. They have been overrated for years and are a cash cow for the companies who make them. These companies have spent millions on extension trials trying to prove that their CRAB is better than the next guy's! And Biogen has been right in there with Avonex.

What is the overall safety profile of all the ABCR drugs in regards to the collateral damage incurred by these ineffective MS drugs relative to the actual damage caused exclusively by the disease itself within the entire MS population?

You really don't think that the CRAB drug makers would give us that information, do you? I know 3 MS patients who took a CRAB and saw their disease progress so quickly and aggressively it made your head spin!!

At the same time, I also don't trust Biogen when it comes to divulging all the info on Tysabri. Their reputation in the medical world is quite poor in this area. Let's just say that if they had handled the introduction of Tysabri differently, I believe the drug would be in use today under much stricter guidelines.

Harry

Harry, nice one. I wasn't trying to convince you of something you already knew. I was trying to tell you something new. I reworded my previous question into a statement. Now read it again and tell me what you think:

"Tysabri showed 28% SUSTAINED disease reversal with 100% mitigated disease progression in the AFFIRM trial as never seen before efficacy in any of the MS CRAB drugs."

You don't have to convince me about the minimal efficacy of the CRABs. They have been overrated for years and are a cash cow for the companies who make them. These companies have spent millions on extension trials trying to prove that their CRAB is better than the next guy's! And Biogen has been right in there with Avonex.

What is the overall safety profile of all the ABCR drugs in regards to the collateral damage incurred by these ineffective MS drugs relative to the actual damage caused exclusively by the disease itself within the entire MS population?

You really don't think that the CRAB drug makers would give us that information, do you? I know 3 MS patients who took a CRAB and saw their disease progress so quickly and aggressively it made your head spin!!

Good one Harry. You know of 3 MSers. I know of thousands and thousands. What took you so long to figure that out? Don't you think the ABCR companies had us MSers really fooled? It wasn't hard. Those approved MS drugs is all we've had. If MS was a type of deadly CNS cancer, most of us would have been dead by now.

At the same time, I also don't trust Biogen when it comes to divulging all the info on Tysabri. Their reputation in the medical world is quite poor in this area. Let's just say that if they had handled the introduction of Tysabri differently, I believe the drug would be in use today under much stricter guidelines.

Harry, at some point you should consider trusting some one more than just yourself. I think I'll trust anyone who had least tried the drug and all the docs trying to figure out what caused the PML in the Sentinel study. It doesn't appear that Tysabri was the direct cause of PML. Tysabri may have been a convenient accomplice with Avonex while possibly being dosed to a couple of trial patients who may have had another form of demyelinating disease other than typical MS. So in other words, if the experts can't or refuse to figure why PML occurred in the Sentinel study, I feel very confident to safely resume dosing of Tysabri as a standalone monotherapy for my MS.


Later Harry

if the experts can't or refuse to figure why PML occurred in the Sentinel study, I feel very confident to safely resume dosing of Tysabri as a standalone monotherapy for my MS.

Put me in the chair and hook up my IV! I am totally ready! My neuro asks me everytime i talked to him if I know any more news about Tysabri! We have a running joke that I will know about its return before he does. He is waiting and ready to write the orders as soon as we hear of its availability. No questions RE safety from either of us. We will be working together to keep tabs on everything...and watch my progress...for once instead of...my progression! woo hoo!
Heather[/quote]

"Bull",

"Tysabri showed 28% SUSTAINED disease reversal with 100% mitigated disease progression in the AFFIRM trial as never seen before efficacy in any of the MS CRAB drugs."

I've looked at a number of abstracts and other articles re: Tysabri and can't find anything about your comment above. Where was this taken from?

Good one Harry. You know of 3 MSers. I know of thousands and thousands. What took you so long to figure that out? Don't you think the ABCR companies had us MSers really fooled? It wasn't hard. Those approved MS drugs is all we've had. If MS was a type of deadly CNS cancer, most of us would have been dead by now.

I wasn't talking about those patients that I have read about but of 3 people that I know personally and saw exactly what happened to them. When the CRABs started to appear in the 90's, it didn't take long to realize what a sales job was being performed by the companies who made them. I can remember attending one of the "Research Updates" sponsored by Berlex, (Betarseron). The neuro pointed out all the nice stats on his chart on how good this drug was for MS patients. In the question period afterwards, I asked him if any of the trial patients actually felt "well" while using the drug. His response was "no"!! You could hear a collective "sigh" in the audience and then dead silence. The glare I received from the neuro wasn't exactly "friendly"!

Harry, at some point you should consider trusting some one more than just yourself. I think I'll trust anyone who had least tried the drug and all the docs trying to figure out what caused the PML in the Sentinel study. It doesn't appear that Tysabri was the direct cause of PML. Tysabri may have been a convenient accomplice with Avonex while possibly being dosed to a couple of trial patients who may have had another form of demyelinating disease other than typical MS. So in other words, if the experts can't or refuse to figure why PML occurred in the Sentinel study, I feel very confident to safely resume dosing of Tysabri as a standalone monotherapy for my MS.

I said I didn't trust Biogen and that lack of trust comes from hearing comments from people in the MS medical world make the same comment....including my wife's neuro who actually conducted Tysabri clinical trials. Please don't twist my words and say that I don't trust anyone.

You say that Tysabri doesn't appear to have been a direct cause of PML and that it "may" have been a convenient accomplice with Avonex. Well there have been some docs who don't agree with that statement and say that the only common denominator here so far is Tysabri. But at this point in time, nobody really knows, do they? MS patients didn't hear about PML until Tysabri came along. This drug is a powerful, immune system altering medication and it needs a lot more study done on it....far more than Biogen/Elan gave it prior to approval and general use. The good thing that has come out of all of this is that when Tysabri starts to get used again, the monitoring of MS patients on it will be far greater than ever before. I'm sure that the FDA will mandate that and will require a "black box" warning for the drug. This is what should have happened in the first place.

Take care.

Harry




Later Harry[/quote]

MS patients didn't hear about PML until Tysabri came along. This drug is a powerful, immune system altering medication and it needs a lot more study done on it....far more than Biogen/Elan gave it prior to approval and general use. The good thing that has come out of all of this is that when Tysabri starts to get used again, the monitoring of MS patients on it will be far greater than ever before. I'm sure that the FDA will mandate that and will require a "black box" warning for the drug. This is what should have happened in the first place.

The Sentinel trial has also shown a small margin of scientific and human error may exist in professional MS patient diagnostics, monitoring, screening and available concomitant drug therapy.

Logical deduction: If many common presenting symptoms of MS are remotely similar to forms of other active, bacterial or viral demyelinating disease such as PML, what fraction of all deceased MSers may have been historically assumed to have died from complete shut down or failure of vital bodily functions controlled by their once healthy CNS? Do their death certificates simply state MS as the cause of death? I'm curious.

Please don't twist my words and say that I don't trust anyone.

Harry, no one twisted your words. You're the one that gets to type what ever you feel like debating about at any given time. Have you noticed that I have the same equal time you are afforded in this unbiased-open forum?

Then you amused me with this very interesting comment:

MS patients didn't hear about PML until Tysabri came along.

Harry, its about time us MSers and all of all of our so-called specialists, experts, and practitioners learned about PML. Harry, drug induced PML has also been occurring in the non HIV/AIDs patient population for many years. The drug induced PML safety issue is not only an issue with MS patients! Think about it.


You also said this:

I'm sure that the FDA will mandate that and will require a "black box" warning for the drug. This is what should have happened in the first place.

Let's assume that you really know what you're talking about when it comes to making statements about FDA regulatory decisions.

PML occurred in a combinative or concomitant drug therapy MS clinical trial that was also mandated by the FDA for the drug's BLA approval. Would it make sense that pharmakinetics and immunological suppression came into play because PML hadn't occurred in the several hundred patient years of Tysabri monotherapy dosing since the late 90's? What about all the other cases of PML that had nothing to do with Tysabr/Avonex induced PML within the public domain but outside of the MSer population?

Harry, if what you're saying is true about black box labeling for the new drug, shortly following its commercial re-introduction you might also be likely to see newly revised black labels submitted for beta interferon 1A, prednisone, and IVIG. How about any or all currently avialable drugs without any black label that have ALREADY been linked to drug-induced PML and patient death in the entire patient population?

And in the end if it comes back approved under a black box label like you have said, I do know of a few MS patients that will go back on the monotherapy drug once again, regardless. Our choice.

Harry, I would really rather have YOU look for the information about the sustained disease reversal and mitigation of disease progression in the AFFIRM trial of natalizumab. I'll give you a few days then about the time you cry uncle the FDA will have already granted accelerated or priority approval for the natalizumab sBLA and new label previously submitted by Biogen on Sept 26th. But hey, since you're a nice guy I'll give you one clue to help you along: ECTRIMS 2005 and 2/3 year clinical data safety profile endpoints met or exceeded.

Good day Harry, enjoy.

"Bull",

Logical deduction: If many common presenting symptoms of MS are remotely similar to forms of other active, bacterial or viral demyelinating disease such as PML, what fraction of all deceased MSers may have been historically assumed to have died from complete shut down or failure of vital bodily functions controlled by their once healthy CNS? Do their death certificates simply state MS as the cause of death? I'm curious.

This brings up an interesting scenario. Usually, before an MS patient is allowed into any kind of clinical drug trial, they must have a definite diagnosis of MS. We all know that this disease can sometimes be very difficult to diagnose and that is why so many patients remain in "limbo". So unless the neuro is certain, he won't give the patient a MS diagnosis and certainly wouldn't recommend him/her into a trial. Yet we know that Anita Smith, the Avonex/Tysabri trial patient who died from PML, didn't have MS! So how many other similar "MS" patients are part of this scenario? Hopefully very few.

Harry, no one twisted your words. You're the one that gets to type what ever you feel like debating about at any given time. Have you noticed that I have the same equal time you are afforded in this unbiased-open forum?

Well, you suggested that I start trusting someone other than myself. It was in reply to my comment on not trusting Biogen. I got the inference from your comment that I don't trust anyone which is simply not true. If I misinterpreted what you said, then I offer my apology.

Harry, its about time us MSers and all of all of our so-called specialists, experts, and practitioners learned about PML. Harry, drug induced PML has also been occurring in the non HIV/AIDs patient population for many years. The drug induced PML safety issue is not only an issue with MS patients! Think about it.

Prior to Feb 2005, if one were to look at the many MS internet forums or read the hundreds of CRAB trials, you likely wouldn't see the word "PML". There was no reason for MS patients to be concerned about it. But obviously that has changed!

As for the Black Box label....hey Bull, I'm not the one who is advocating that. That information has come from many of the press releases and articles I have read about the possibility of Tysabri returning. I'm simply relating what the "experts", both in the financial and medical world, have stated.

I've searched the ECTRIMS conference info high and low and haven't located the info about the disease reversal for Tysabri. I'll take your word for it but find it interesting that information, to my knowledge, was never published anywhere prior to the ECTRIMS conference. Is this data new?

So you're betting that the FDA is going to re-approve Tysabri very soon? I'm thinking it will be approved... but later rather than sooner.

Take care.

Harry

So you're betting that the FDA is going to re-approve Tysabri very soon? I'm thinking it will be approved... but later rather than sooner.

well....fda granted priority review as of yesterday...so sooner is on the table