Tovaxin depletion of lymphocytes mediating autoimmune diseases such as MS

[Wise Young]

Tovaxin is a drug that depletes cells that mediate lymphocytes the cause autoimmune diseases such as MS. The first phase 1/2 trial results are being reported in an upcoming MS meeting.

http://home.businesswire.com/portal/...ewID=news_view

August 10, 2005 04:00 AM US Eastern Timezone

PharmaFrontiers to Present Tovaxin(TM) Research at International Multiple Sclerosis Meeting

THE WOODLANDS, Texas--(BUSINESS WIRE)--Aug. 10, 2005--PharmaFrontiers Corp. (OTCBB:PFTR), a company involved in the development and commercialization of cell therapies, announced today that their research of their Phase I/II clinical trials of Tovaxin(TM), a novel T cell therapeutic vaccine for Multiple Sclerosis, has been accepted for presentation at the 21st Congress of the European Committee/10th Annual Meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis to be held September 28 - October 1, 2005, in Thessaloniki, Greece. The interim trial results have indicated that the treatment appears safe and well tolerated.

Tovaxin(TM) is a trivalent formulation of attenuated myelin-peptide reactive T cells (MRTCs), which are derived from peripheral blood and produced ex vivo as myelin basic protein (MBP), proteolipid protein (PLP) and myelin oligodendrocyte glycoprotein (MOG) reactive T cells.

In addition to the safety and tolerance indications, the study concluded that MRTCs in patients with MS can be depleted by Tovaxin(TM) treatment. Multiple Sclerosis Impact Scale (MSIS) and Kurtzke Expanded Disability Status Scale (EDSS) clinical measures are improved.

"Having the opportunity to present such encouraging data from Tovaxin(TM) clinical trials at such a prestigious international MS meeting is a great honor and very exciting for our researchers and all of the PharmaFrontiers staff. The acceptance of our abstract confirms our confidence as we move ahead with the development of Tovaxin(TM) for the treatment of patients who are in the early stages of MS," said David B. McWilliams, chief executive officer of PharmaFrontiers. "With our clinical development partner, INC Research, Raleigh, NC, we plan to initiate this pivotal Phase IIb/III clinical study of early relapsing MS patients by the first quarter of 2006 to advance our understanding of this novel T cell therapeutic vaccine for MS."

The presentation, "Autologous T Cell Therapy in Multiple Sclerosis: An Open Label Safety and Dose Range Study," is authored by Brian D. Loftus, MD, director of Neurology Research and Diagnostic Clinic of Houston (and principal investigator for PharmaFrontiers' two current Phase I/II clinical trials of Tovaxin(TM)), Mitzi Montgomery, DVM, PhD, PharmaFrontiers VP of Discovery and Preclinical Development, and Jim C. Williams, PhD, PharmaFrontiers Chief Operating Officer.

Previous studies of T cell vaccination conducted by Jingwu Zhang, M.D., Ph.D., Director of Research, Baylor Multiple Sclerosis Center at The Methodist Hospital, and colleagues have shown that a monovalent (MBP selected MRTCs) formulation was safe and potentially beneficial in relapsing remitting and secondary progressive patients.

[IHaveMS-com]

Hi to all,

I am in the FDA trial for Tovaxin, 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 http://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 http://www.timswellness.com from June 2004 to the present. I am a little behind on the second website. My Dad and I work on it together.

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 http://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. The company has a nice animation of how Tovaxin works at http://www.pharmafrontierscorp.com/toxavin.php

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.

After presenting the data at the International Meeting at the end of September http://home.businesswire.com/portal/...58&newsLang=en , the company hopes to use these results to gain FDA approval to start phase IIb/III trials. Enrollment will start at the end of the year in Texas and at the other sites (I don't know where) after the first of the year.



The company is PharmaFrontiers and the company website is http://www.pharmafrontierscorp.com/ The CEO is David McWilliams dmcwilliams@pharmafrontierscorp.com. The principal investigator for the current studies is Dr. Brian Loftus BLoftus@diagnosticclinic.com The study is posted on his website http://www.loftusmd.com/Articles/MS/...ccineRRMS.html


Best regards, Tim

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This is a short comparison of 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.ult...noclonals.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.

[Wise Young]

Tim, thank you very much for your post. This sounds very exciting. Wise.

[Sue Pendleton]

Originally Posted by Wise Young

Tim, thank you very much for your post. This sounds very exciting. Wise.

Sounds incredible! Would this become something that could be used to stop MS in its more advanced forms and then remyelination therapies could "fix" the disability to the brain and body?

[IHaveMS-com]

Hi Sue,

If you can arrest the progression of the disease, the body will attempt to restore itself. It is common to see some disease reversal in people receiving Tovaxin. The disease reversal was also seen in the early studies of Tovaxin done at Baylor in the late 1990s. I have a link to those studies on the links page of http://www.ihavems.com. They are the first 3 links. Tovaxin has come a long way since those reports were written.

The purpose of Tovaxin is to deplete the myelin reactive T-cells to near zero. With no more attacks, there is no more depletion of myelin. The amount of remyelination that can occur would depend on the length of time since the demyelination, the patient's age, and other health related factors.

Besides the animation of how Tovaxin works at http://www.pharmafrontierscorp.com/toxavin.php there is an animation of the autologous adult stem cell technology that the company is developing. Currently they have produced islet cells http://www.pharmafrontierscorp.com/diabetes.php that when challenged with glucose will secrete insulin and heart muscle cells to repair heart attacks. I would hope they will develop cells to remyelinate in the future.

Best regards, Tim

[Sue Pendleton]

Thanks for the information Tim. I have a relative with chronic progressive and while normally MS tends to hit the body and/or eyes first hers hit her eyes and brain. I thought I was up on the major research in MS but missed this completely. Thanks and I will pass this information on to her family. She was in the first clinical trials of Beta-seron way back when.