Tuesday, March 15, 2005

Post Tysabri (Natalizumab): What Choices in M.S. Treatment?

The Consumer: Exploring Choices for M.S.
By MARY DUENWALD
The New York Times
15 March 2005

[snip]

An estimated 5,000 patients who had been taking Tysabri since the Food and Drug Administration approved it in late November are now advised to see their doctors for physical examinations and to consider trying other drug treatments to keep their multiple sclerosis in check or perhaps returning to them.

Those who had been in the clinical trial will be given magnetic resonance scans and other tests to check for P.M.L.

The good news, doctors say, is that most patients who took Tysabri alone and only since November are unlikely to develop progressive multifocal leukoencephalopathy.

"If there is any connection between Tysabri and the leukoencephalopathy, that risk should have been removed by stopping the drug," said Dr. Patricia Coyle, director of the multiple sclerosis clinic at the State University of New York at Stony Brook. "Patients don't have to worry that two months or six months from now they're going to come down with P.M.L."

[snip]
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1 Comments:

Blogger IHaveMS-com said...

Hi To All,

I am in an FDA trial for an MS vaccine. The vaccine appears to have arrested my disease and has done the same for the other people in the study. I have two small websites that show a timeline of events. The first one is www.ihavems.com It starts with the first injection and goes for 18 months. My websites are little 10-page boilerplate sites, so my timeline continues on a second website www.timswellness.com from June 2004 to the present. My Dad and I work on the sites together.

The difference between Tysabri and Tovaxin. Tysabri was approved last November for use with people suffering from MS. It reduces the number of attacks by 2/3 verses 1/3 with the current drugs. It reduces brain liaisons by 90% and reduces the progression of disability by 44%. It got fast tracked and was heralded as the next generation of MS treatments. It was the drug that Tovaxin would have gone head-to-head with in Phase III clinical trials.

What is Tysabri? It is a Monoclonal Antibody http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/M/Monoclonals.html -- an antibody that is mass-produced in the laboratory from a single clone and that recognizes only one antigen. Monoclonal antibodies are typically made by fusing a normally short-lived, antibody-producing B cell to a fast-growing cell. The resulting hybrid cell multiplies rapidly; creating a clone that produces large quantities of the antibody.

MS is considered to be an autoimmune disease in which the person's immune system attacks the brain and/or spinal cord. Tysabri appears to work by binding to these immune system cells, thus preventing them from traveling to the brain where they can cause damage.

Antibodies are proteins produced by a person's immune system to fight foreign substances, such as infections. Monoclonal antibodies, such as natalizumab (Tysabri), can be produced in large quantities in cell culture in a laboratory setting. They can be designed to bind to proteins on the body's normal cells. By recognizing and attaching to these proteins, monoclonal antibodies can interfere with (or alter) normal or abnormal cellular responses. In this way, monoclonal antibodies may be useful in the treatment of certain diseases such as MS.

What killed the patient? The reports involved at least three cases of progressive multifocal leukoencephalopathy (PML) http://healthlink.mcw.edu/article/921450160.html , a rare but often fatal disease that affects the nervous system. In two of the cases, the patients had been taking Tysabri for more than two years in combination with another MS drug, Avonex. In the third case, the person was taking only Tysabri and was in a Crohn's Disease study.

It is suspected that Tysabri or the combination of Tysabri and Avonex allowed this rare viral infection to take hold. 80% of all adults have been exposed to this virus, but it is rare for someone to be affected by it. Someone with a compromised immune system, such as AIDS, would be a candidate to get this. Possibly Tysabri or the combination of the two drugs altered the patients immune system enough to allow the virus to attack.

PML is a demyelinating disease and it was first thought that these patients were having an MS attack. There is no known cure for PML and diagnosis is usually done by autopsy. It may be possible to diagnose it with a spinal tap, but currently, an MRI assessment is used when PML is suspected.

What does Tysabri's withdrawal mean to the approval of Tovaxin, and whether or not Tovaxin will get fast tracked? Tysabri has no bearing on whether or not Tovaxin gets approved. Tysabri is a monoclonal antibody and Tovaxin is an autologous T-cell elimination. Tysabri is a laboratory created antibody that attaches itself to T-cells thus preventing them from crossing the blood-brain barrier. It stops almost all T-cell from crossing, not just the bad ones.

Tovaxin http://www.pharmafrontierscorp.com/toxavin.php is a vaccine, which uses the patient's own blood. Like a flu shot, it makes the body form antibodies against a select T-cell, which attacks myelin. It does not interfere with any other T-cells and has no effect on the blood-brain barrier. There is virtually no health risk. The typical frequency of myelin reactive T-cells in the blood of a patient with MS is about 1 to 2 per million. Eliminating this small fraction of T-cells from a person's immune system has very little effect.

Since Tovaxin is autologous and posses little health risk, if a small portion of patients show improvement (10%), it will get fast tracked. The current drug escalation trials have show that it is safe and almost all of the patients have shown improvement.

The study that I am in is small, only 9 to 15 patients. There is a concurrent one that is retreating any of the 114 patients that were in the MS vaccine study done at Baylor in the late 1990s. The vaccine is called Tovaxin and you can see an animation of how it works at http://www.pharmafrontierscorp.com/toxavin.php

All of the patients in my study have responded positively. There is one person in the study who has primary progressive. She did not respond at first, but they have discover the peptide sequence for the CD-8 T-cells that cause PP. Since then she has seen her EDSS go down by 0.5. My EDSS has gone from 5.5 to 3.0.

I am actually out doing things again. I just returned from a solo trip to see some friends in San Francisco. This is amazing, since two years ago, my parents were taking me from our home in Michigan to Houston in a wheelchair.

Tovaxin is an autologous vaccine. That means they take some of my blood, cull out the T-cells and introduce them to human myelin. Those that react to the myelin are culled out and replicated. Once there are enough for the vaccine, about 45 million cells, the T-cells are irradiated so that they are still alive, but cannot reproduce. That is the vaccine.

The vaccine is injected just under my skin, you can see some pictures at www.timswellness.com , and the body treats these T-cells as a foreign invader and makes antibodies to eliminate only these specific T-cells. These antibodies not only take out the T-cells from the vaccine, but also eliminate all of that same type of T-cell throughout my body.

The body produces 2 to 3 trillion red blood cells per day. I am not sure how many T-cells are produced per day, but if 1 or 2 per million are troublemakers, that means there are hundreds of millions of myelin reactive T-cells floating around in the blood stream of someone with MS. A flare is when the body produces too many of these bad T-cells. No one is sure why this happens, but it may be caused by an upper respiratory infection, or a cold sore, or some other immune response that triggers the body to produce T-cells that mistake myelin as something bad.

By eliminating these 1 or 2 per 1 million T-cells does not compromise the immune system, but it does eliminate all of the T-cells that destroy the myelin. No bad T-cells means no more attacks. Anyone on Tovaxin will need to get a booster twice a year to keep the antibodies at a level sufficient to continue to eliminate all of the myelin reactive T-cells as they are produced. This is just like a flu shot.

I think about 30 to 40% of the damage that was done by the attacks has been reversed. The body will repair itself, as long as the attacks stop. I am helping myself by doing a lot of exercising and activities that improve my small motor skills.

I am doing many things that I was no longer able to do. When I started the vaccine, my parent's were cutting my food and feeding it to me. I am able to cut my own food, and today, I peeled some shrimp. Realizing that I can again do something as insignificant as peel a shrimp really makes me feel good. I used to wonder why people got so excited to see a disabled family member regain some little ability, now I understand, and I understand why my family is trilled at even my smallest improvement.

Phase III should begin at the end of this year or the beginning of 2006. http://biz.yahoo.com/bw/050608/85342.html?.v=1 There will be many sites throughout the US and in some foreign countries. You can watch the companies webpage for updates http://www.pharmafrontierscorp.com/

Best regards, Tim

1:46 PM  

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