Tovaxin Phase I/II Results

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Tovaxin Phase I/II Results

Postby dignan » Fri Jun 03, 2005 8:00 am

The results are good, but the number of patients assessed in this report is tiny! Oh well, they say they are planning to go to Phase II/III in late 2005 or early 2006!


PharmaFrontiers Announces Positive Interim Results of Two Phase I/II Clinical Trials for Multiple Sclerosis

June 3, 2005 -- BUSINESS WIRE -- PharmaFrontiers, a company involved in the development and commercialization of cell therapies, announced that interim results of Tovaxin(TM) in two Multiple Sclerosis (MS) Phase I/II open-label studies indicated that it was safe and well tolerated, and patients showed positive responses. All patients enrolled in the studies had received prior standard of care therapy for MS and were in the relapsing remitting or secondary progressive stages of MS.

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.

An interim analysis of a Phase I/II dose-escalation study of six evaluable patients, half of whom received a low dose (six to nine million MRTCs) and the other half received a mid dose (30-45 million MRTCs) during the six-month evaluable period, indicated that the Tovaxin(TM) therapy reduces peripheral blood MRTC levels in concert with improvements in disability scores Kurtzke Expanded Disability Status Scale (EDSS) as well as in disability neurological assessments for psychological scores Multiple Sclerosis 29 point Impact Scale (MSIS-29). The exacerbation rate over the previous two years for the patients was 1.18 per year. Only one treated patient reported an exacerbation during the six-month evaluable period in this study. All of the related adverse events were mild or moderate in severity.

An interim analysis of a Phase I/II extension study of nine evaluable patients, who received two doses (30-45 million MRTCs) during the six-month evaluable period, indicated a mean percent reduction in MRTCs observed at three and six months for all three categories of MRTCs. A statistically significant percent (greater than minus 60%) reduction in PLP T cells was observed at three and six months. There was a percentage reduction (greater than or equal to minus 21%) in MBP and MOG T cells at three and six months. Percentage reductions in the EDSS and MSIS-29 physiological scores from baseline were observed at the three and six-month follow-up visits. The exacerbation rate over the previous two years for the patients was 0.85 per year. There were no exacerbations during the six-month evaluable period in this study. The most common adverse event was injection site pain, reported by four patients. Adverse events reported by two patients included muscle weakness, abnormal vision, anorexia, pharyngitis / nasopharyngitis, neuropathy and paresthesia. All of the related adverse events were mild or moderate in severity.

"We are very encouraged by these preliminary MRTC levels, which demonstrated a dose response and large mean percentage reductions from baseline at follow-up visits during the six-month period," said David B. McWilliams, chief executive officer of PharmaFrontiers. "Accordingly, we plan on beginning our Phase IIb/III clinical trials by the end of 2005 or early 2006." The Company's preliminary results and clinical development plans will be discussed at a June 4 luncheon at the 19th Annual Meeting of the Consortium of Multiple Sclerosis Centers in Orlando, FL.

"These data, combined with the strong safety profile of Tovaxin(TM), should be welcome news to all MS patients and their families, especially in light of disappointing product news of this past year," Mr. McWilliams added.

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Postby Arron » Fri Jun 03, 2005 1:57 pm

very interesting... i like the mention of EDSS reduction
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Tovaxin study and EDSS

Postby IHaveMS-com » Mon Jun 13, 2005 7:45 am

Hi, I am in the current FDA trials for Tovaxin, and it is true, my EDSS has gone from 5.5 to 3.0 in the last 18 months. I have a small website about my timeline in the study at http://www.IHaveMS.com There was a presentation on Tovaxin at the National MS Centers Meeting a week ago. This is a link to a synopsis of what was said. http://biz.yahoo.com/bw/050608/85342.html?.v=1
Best regards, Tim
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Postby bromley » Mon Jun 13, 2005 8:47 am

Dear all,

It's great news that Tim's EDSS has gone from 5.5 to 3.0 in the last 18 months since being on Tovaxin. Lab Rat has also seen a reduction in his EDSS since starting Campath (EDSS dropped from 3.0 to 1.0 and no relapses).

Both of these treatments target the T Cells that are considered responsible for the attack on myelin. What does this say about MS being an auto-immune disease (or not)?

Discussions have taken place on this site as to whether MS is an auto-immune disease or a neuro-degenerative disease. If it is an underlying neuro-degenerative disease (with immune system involvement / inflammation etc being a 'side-show), why would improvements be seen in EDSS by affecting the T Cells?

Any thoughts on this would be welcome.

What we do appear to have are two potential future treatments which are good at stopping relapses and letting some repair take place. Time will tell if the good results continue - let's hope they do. The data to date are limited, but they appear to offer more efficacy than the CRABS (although long term risks still to be assessed).

Bromley
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Tovaxin and Campath-1H reduce EDSS

Postby IHaveMS-com » Mon Jun 13, 2005 1:39 pm

Hi To All,

Multiple Sclerosis is both an autoimmune disease and a neurodegenerative disease. It is generally considered to be an autoimmune disease which results in neurodegeneration.

A neurodegenerative disease is a disorder caused by the deterioration of certain nerve cells. Changes in these cells cause them to function abnormally, eventually bringing about their death. The diseases, Alzheimer's, Parkinson's, Creutzfeldt-Jakob, Amyotrophic Lateral Sclerosis (Lou Gehrig's Disease), Huntington's Disease, Frontotemporal Dementia (Pick's Disease), Prion Diseases as well as Multiple Sclerosis, are due to neuronal degeneration in the central nervous system.

An autoimmune disease is when your immune system attacks itself by mistake. Autoimmune diseases can affect many parts of the body, like nerves, muscles, endocrine system, connective tissue, and digestive system. Some of the more common autoimmune diseases are Multiple Sclerosis, Type One Diabetes, Rheumatoid Arthritis, Psoriasis, Graves’ Disease, Lupus, and Crohn's Disease. In each of these diseases the body own T-cells misidentify myelin, islet cells, etc., and attack those cells as if they were an unwanted invader.

The two treatments both target the T-cells that are considered responsible for the attack on myelin. The difference is that Campath-1H is a monoclonal antibody (Tysabri is a monoclonal antibody) and Tovaxin is a targeted T-cell elimination.

A targeted T-cell elimination is where a vaccine is made from the person's own myelin-reactive T-cells. A sample of blood is taken from the patient and the white blood cells are removed. The white blood cells are then introduced to human myelin, and those that react to it are culled out. This small amount of cells, usually 1 or 2 per 1 million are grown in the lab. Once the number of cells has reached 100 million, a dose (30 to 45 million cells) is removed and attenuated (radiated enough to break the DNA chain so that they cannot replicate, but still alive). A vaccine from live cells is like the difference between the Salk and Sabin Polio vaccines. This causes a much greater immune response. It is this immune response that forms antibodies that specifically target the patient's myelin-reactive T-cells. Once the patient has a sufficient number of these antibodies, the number of myelin-reactive T-cells approaches zero and no more myelin destruction occurs.

The improvement in EDSS from both treatments is probably due to the fact that the disease progression has been halted. If the disease is arrested, the body can begin rebuilding. and your EDSS should go down. Both of these treatment go to the root of the problem and eliminate the T-cells that cause the myelin destruction. Tovaxin eliminates 1 or 2 per 1 million T-cells. From what I have read about Campath-1H, it appears that the treatment eleminates all of the patents T-cells, not just the bad one. I will paste in a portion of an interview from July 21, 2003 in which Dr. Jacobs describes the history of Campath-1H and how it works.

Best regards, Tim http://www.IHaveMS.com
---------------------------------------------------------------
Reported July 21, 2003
New Hope for MS -- Full-Length Doctor's Interview

In this full-length doctor's interview, Daniel Jacobs, M.D., explains how a new drug targets destructive white blood cells in MS patients and could stop the disease in its tracks. Ivanhoe Broadcast News Transcript with
Daniel Jacobs, M.D., Neurologist,
TOPIC: New Hope for MS

Tell me about the history of this new treatment for MS.
Dr. Jacobs: Campath-1H is a monoclonal antibody that attacks T-cells, which are the cells that attack the myelin in multiple sclerosis. This drug is given as an infusion. Patients don’t have to get daily shots. They can get an intravenous infusion of drug for five days a year without shots, and it will reduce their relapses and improve the MRI signs of multiple sclerosis. We have not studied it in a huge number of patients yet, so we cannot make any claims about efficacy. But the pilot studies suggest that it’s very effective and maybe more effective than the existing treatments for multiple sclerosis.

Explain to me how Campath-1H works.
Dr. Jacobs: The drug is a new type of drug called a monoclonal antibody that attacks certain types of white cells that attack the brain and spinal cord and cause multiple sclerosis. It helps prevent the attacks of multiple sclerosis. The drug is a new class of drug called monoclonal antibodies, which attack certain white blood cells that attack the brain and spinal cord and turn these white blood cells off. As a result, multiple sclerosis relapses can be eliminated.
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Postby finn » Thu Jun 16, 2005 5:33 am

Sorry, time to leave the board.

-finn
Last edited by finn on Sun Aug 28, 2005 2:35 pm, edited 1 time in total.
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Postby bromley » Thu Jun 16, 2005 6:44 am

Finn,

Thanks for your excellent summary and the list of questions that still need to be answered. I am seeing this term 'reversible' disability more and more, and you might be right that this might be the disability initially caused by de-myelination (re-myelination helping the symptoms). Some of the research suggesting that atrophy is occuring in other areas (not just where there are lesions / de-myelination) makes this disease look much more sinister than previously thought, as does the research showing that grey matter is also involved. One thing I am learning about MS is that it is always much worse than you first imagined.

The list of questions about this disease appears to be endless. Others might include:

- Is the Secondary Progressive MS stage the same as Primary Progressive (is the difference that there is a period for most sufferers where relapses occur before they move to the progressive stage)?

- Why do some have a very aggressive disease course (some die 10-15 years after onset e.g. Jacqueline du Pre)) while others survive 30-40 years after onset?

- Why do some get the disease in early teens (or earlier) while others get it later in life (40s-50s)?

I could go on but I won't. If only the research community could come up with one clear answer to one of these questions. On the positive(ish) side -we now have some drugs (in trial) that can pretty much stop relapses, a lot of thought is being given to how to prevent neuro-degeneration, stem cells (may) in the future repair some of the damage done.

Regards

Bromley
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Postby IHaveMS-com » Thu Jun 16, 2005 8:18 am

Hi Bromley,

- Is the Secondary Progressive MS stage the same as Primary Progressive (is the difference that there is a period for most sufferers where relapses occur before they move to the progressive stage)?

Relapsing remitting patients will usually transition into secondary progressive within 5 to 10 years after the diagnosis of MS. The two forms of MS both involve CD-4 T-cells. In SP the patient is no longer seeing remissions. Primary progressive differs from RR and SP in that the type of T-cells are CD-8.

- Why do some have a very aggressive disease course (some die 10-15 years after onset e.g. Jacqueline du Pre)) while others survive 30-40 years after onset?

The average life span of someone with MS is only decreased by approximately 3%, except in the case of primary progressive.

- Why do some get the disease in early teens (or earlier) while others get it later in life (40s-50s)?

MS has been diagnosed as young as 5 years old. Pediatric MS is very difficult to diagnose because the body is constantly myelinating until at least 18 years of age. Why is the age of onset different for different people? A guess would be that it is related to when sufficient expose to possible triggers have occurred, only a guess.


-we now have some drugs (in trial) that can pretty much stop relapses, a lot of thought is being given to how to prevent neuro-degeneration, stem cells (may) in the future repair some of the damage done.

There have already been some mouse studies that have demonstrated that when autologous adult stem cells were injected into the tail of the mouse, the cells migrated to the brain and remyelinated the damaged areas. Human remyelination is much farther off than arresting MS. By looking at rehabilitation of stroke patients, we see that the brain has a great degree of plasticity and you can build new pathways around areas that have been demyelinated. Starting with some physical therapy and continuing with a structured exercise program would be something to consider.

Best regards, Tim
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