This Is MS Multiple Sclerosis Knowledge & Support Community

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 have a thread "Tovaxin new MS vaccine" going on Montel's Corner. http://www.spotlighthealth.com/common/f ... ?m=2&sb=12 In it, I discuss being in an FDA trial for Tovaxin, which is a vaccine that targets and eliminates the myelin reactive T-cell that cause MS.

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.


PharmaFrontiers was asked to be a presenter at the 21st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in Thessaloniki Greece. I will paste in the press release and the poster session from Greece. It showed a 92% decrease in attacks compared to the CRAB drugs 33% and a decrease in disability where the CRAB drugs have none. The company hopes to start phase IIb/III trials at the end of this year. Enrollment will start 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 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/Tce ... eRRMS.html

To get on the list for the next trial of Tovaxin, the best person to email is Shannon Inman sinman@pharmafrontierscorp.com . She works for the company and is keeping a file of interested people. There will be sites throughout the US and some in Canada. There may be some outside of North America.

Best regards, Tim
-----------------------------------------
<shortened url>
PharmaFrontiers Presents Positive Tovaxin(TM) Research at International Multiple Sclerosis Meeting
Monday October 3, 5:00 am ET


THE WOODLANDS, Texas--(BUSINESS WIRE)--Oct. 3, 2005--PharmaFrontiers Corp. (OTCBB:PFTR - News), a company involved in the development and commercialization of cell therapies, presented positive interim research findings of its Phase I/II clinical trials of Tovaxin(TM), a novel T cell therapeutic vaccine for Multiple Sclerosis on Friday, September 30, 2005, at the 21st European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and the 10th Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) congress held in Thessaloniki, Greece. The trial results not only indicated that the treatment appeared safe and well tolerated with no dose-limiting toxicities, but that Tovaxin depletes the myelin-peptide reactive T cells that may contribute to the Multiple Sclerosis (MS) disease processes.
Tovaxin 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.

The Tovaxin treatment depleted MRTCs in patients with MS. The patients in the trial also had improvements in the Multiple Sclerosis Impact Scale (MSIS), which measures subjective physical and psychological parameters, and the Kurtzke Expanded Disability Status Scale (EDSS), which is an objective measure of the patient's physical disability.

"Seeing safety, tolerance and early effectiveness data at this stage of development is gratifying. More important is seeing the lowering of the MRTCs and the improvement in the clinical measures that reaffirms our belief that Tovaxin may be the key to treating patients who are in the earlier stages of MS," said David B. McWilliams, chief executive officer of PharmaFrontiers. "Based on mounting evidence from our research and others, we believe that autoimmune mechanisms directed at myelin tissue of the central nervous system may play a major role in causing MS.

"With our clinical development partner, INC Research, Raleigh, NC, we plan to initiate a follow-on Phase IIb clinical study of clinically isolated syndrome and early relapsing-remitting MS patients by the first quarter of 2006 to advance our understanding of this novel T cell therapeutic vaccine for MS," said McWilliams.

MRTCs play a critical role in the pathogenesis of MS. Previous T cell therapy pilot studies used a monovalent formulation of attenuated MRTCs to deplete MBP reactive T cells. Because several myelin antigens are described as potential autoantigens for MS, depletion of MRTCs using a trivalent formulation may have enhanced therapeutic effects.

The dose escalation study was designed for patients with relapsing-remitting or secondary-progressive MS, intolerant of, or having failed, current therapy. Blood was obtained from each patient from which T cells reactive to two peptides each of three proteins (MBP, PLP, and MOG) were expanded ex vivo and prepared as a trivalent formulation of MRTCs. The MRTCs were attenuated by Cesium137 irradiation prior to patients receiving subcutaneous injections of either 6-9 million cells (Dose 1) or 30-45 million cells (Dose 2) at weeks 0, 4, 12 and 20. MRTC frequencies were performed at baseline and weeks 5, 13, 21, 28 and 52. Patients were evaluated for changes in EDSS, MSIS and exacerbations.

"Tovaxin is a patient-specific therapeutic vaccination strategy for MS patients. To formulate Tovaxin T cell vaccine, the patient's own myelin peptide-specific activated T cell lines are harvested and attenuated on the day of vaccine administration," said Jim C. Williams, Ph.D., PharmaFrontiers chief operating officer and co-author of the study who presented at the meeting. "The shelf-life of the final product is approximately three days."

The study's results demonstrated that MRTCs in the peripheral blood were depleted in a dose dependent manner and analyses showed reductions in all three types of MRTCs at all follow-up visits. All patients in the Dose 2 group had a 100% reduction in MRTC counts at the week five follow-up visit. Percentage reductions were greater in the Dose 2 group than in the Dose 1 group at every follow-up visit. Correlation between the reduction in overall MRTC frequencies and the physical component of the MSIS (p=0.0086) was strong. There was a trend to improved EDSS (p=0.0561). The annual relapse rate (ARR) for the patients prior two years before therapy was 1.28 and following therapy the ARR was 0.10 (92 percent reduction) adjusted for the number of months in the study. The treatment appears to be safe and well tolerated with minimal adverse events and no dose-limiting toxicities.

"If myelin autoreactive T cells are the basis for MS, then we now appear to have a precision guided treatment to seek out and selectively suppress these T cells," said Brian D. Loftus, M.D., director of Neurology Research at the Diagnostic Clinic of Houston, principal investigator for PharmaFrontiers' two current Phase I/II clinical trials of Tovaxin, and co-author of the study who also presented at the meeting.

The presentation, "Autologous T Cell Therapy in Multiple Sclerosis: An Open Label Safety and Dose Range Study," is authored by Dr. Loftus, Mitzi Montgomery, DVM, Ph.D., PharmaFrontiers vice president of Preclinical Development, and Dr. Williams.

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.

------------------------------------------------------------
21st Congress of the European Committee for the Treatment and Research in Multiple Sclerosis
10th Annual Meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis
<shortened url>
Therapy - immunomodulation - Part II
Friday, September 30, 2005, 15:30 - 17:00
Autologous T cell therapy in multiple sclerosis: an open-label safety and dose-range study
B. Loftus, M. Montgomery, J. Williams (The Woodlands, USA)

--------------------------------------------------------------------------------
Objective: To evaluate the safety of a trivalent autologous T cell therapy (TCT) (Tovaxin™) and the effective dose to deplete myelin peptide-reactive T cells (MRTCs) in Multiple Sclerosis. Background: MRTCs play a critical role in the pathogenesis of MS. Previous TCT pilot studies used a monovalent formulation of attenuated MRTCs to deplete myelin basic protein (MBP) reactive T cells. Because several myelin antigens are described as potential autoantigens for MS, depletion of MRTCs using a trivalent formulation (TF) may have enhanced therapeutic effects.
Design/Methods: Patients with relapsing remitting- or secondary progressive-MS intolerant of or having failed current therapy donated blood from which T cells reactive to two peptides each of three proteins [MBP, proteolipid protein (PLP) and myelin oligodendrocyte glycoprotein (MOG)] were expanded ex vivo and prepared as a TF of CD4+ and CD8+ MRTCs. The MRTCs were attenuated by Cesium137 irradiation prior to patients receiving subcutaneous injections of either 6-9 million cells (dose 1) or 30-45 million cells (dose 2) at weeks 0, 4, 12 and 20. MRTC frequencies were performed at baseline and weeks 5, 13, 21, 28 and 52. Patients were evaluated for changes in Expanded Disability Status Scale (EDSS), Multiple Sclerosis Impact Scale (MSIS) and exacerbations.
Results: MRTCs in the peripheral blood were depleted in a dose dependent manner and analyses showed reductions in all 3 types of MRTCs at all follow-up visits. All patients in the dose 2 group had a 100% reduction in MRTC counts at the week 5 follow-up visit. Percentage reductions were greater in the dose 2 group than in the dose 1 group at every follow-up visit. Correlation between the reduction in overall MRTC frequencies and the physical component of the MSIS (p=0.0086) was strong. There was a trend to improved EDSS (p=0.0561). One exacerbation was observed in the dose 1 group. The treatment appears to be safe and well tolerated with minimal adverse events and no dose-limiting toxicities.
Conclusion: MRTCs in patients with MS can be depleted by Tovaxin treatment. MSIS and EDSS clinical measures are improved and the treatment appears safe and well tolerated. A Phase IIb double-blind placebo-controlled trial to study the effects of Tovaxin in treatment of early relapsing MS patients is being planned.

Hi Tim

Thanks for this posting. It is really good news to hear that Tovaxin is working well for you.

I am sure many of us will be keeping an eye on your progress - long may it continue.

best wishes

J.

I know a bit about the immune system and this approach does sound logical.

Did you get any side effects at all? Do you need to take anything else along with these injections?

Thanks to your link, I gave my name for futher studies but I am in Ottawa, Ont. Canada and the main investigator is in Houston! It would be great if my neurologist participated in one of those studies.

Very happy it is doing so much good to you and I will be keeping an eye on your progress. Please keep us up to date. Thanks.

Carole

Hi Carole,

I have had no side effects and do not take anything with the Tovaxin. I do take Zanaflex, but that is for symptoms.

I have heard that McGill will probably be a site, so there should be other sites in Canada. If you neurologist would like to be a site, he can contact the company and indicate his/her willingness to participate. It sounds like there will be 30 to 40 sites for the next study.

Anyone in one of the studies will continue to receive Tovaxin until all of the studies are done and Tovaxin is approved. The IIb study will probably be a one year double blind placebo study with 2/3 getting Tovaxin. After one year, anyone who was receiving the placebo will be given Tovaxin. I assume if there are results similar to mine, the placebo group may get the vaccine even quicker. The phase III study will be Tovaxin against one of the CRAB drugs.

I assume everyone read the press release, but if they didn't, the data presented showed a 92% reduction in attacks and a decrease in disability. In my case, I had no attacks and my EDSS went from 5.5 to 3.0. I was having about 3 attacks per year.

Best regards, Tim

Very encouraging, keep us posted please, this sounds to me like a very solid way of getting rid of this horrible disease. thank, Carole

Tim--read your story not long ago with GREAT interest! In all that I have read about MS, this was by far the most encouraging. I have signed my daughter up for the next trial. However, some questions. I understood this next Phase III would be open lable--no placebos. And what in the H _ _ _ is this about a comparison with a current CRAB drug? Why do they keep doing that? The CRAB drugs were great for their intended purpose--the first drug treatment, ever, for this disease. It has been over 10 years and it is time to MOVE FORWARD to something that is more effective. Why do these drug companies keep trying to hang on to the old stuff? Tovaxin is in a brand new league, all it's own. The combo Phase III is discouraging. Maybe someone more informed than I can understand the need for the inclusion of the CRAB drugs with these "so much newer" drugs.

Chris55,

Why do these drug companies keep trying to hang on to the old stuff?

Because they bring in $4-5 billion a year. Not bad for treatments which have limited efficacy, horrid side-effects etc.


Hope you daughter does well on Tovaxin. It really is time that the treatments moved on and patient outcomes rather than profits came first.


Ian

The other way to look at it is that a Phase III trial has to be placebo controlled. So if you have to have placebo patients, but feel it unethical to have people with a serious degenerative disease not getting treatment, then a good alternative is to do a combination trial where everybody gets a CRAB and some are on the trial drug and some are on placebo in addition to the CRAB. I actually think this is a good thing. But maybe I'm crazy.

Ian--my comments about the CRAB drugs was rather rhetorical. I do understand the "politics" of drug development. There is very little research for "orphan" diseases, which MS was until a very few short years ago. When a company is willing to invest in drug research for this kind of disease, the medical community has no choice but to support them so research will continue. The drug companies spend millions and years developing the drug. They MUST recoup their investment and make a profit. I truly understand all of this. What makes it so difficult is when I look at my precious, beautiful daughter and watch her degrading by the day; watch her pumped full of drugs to offset the drug side effects and disease effects; watch her and her new husband struggle to keep their marriage together; watch her new (very successful) business (dance school) lose over 50% of her students when the word got out (including her neurologists' kids because she dared ask for a 2nd opinion)--I want to SCREAM at the unfairness to ALL of you who must endure this inequity! Sorry about that--just so frustrating!!!

Dignan--combining MS drugs can be dangerous and even fatal, i.e., the Tysabri/Avonex drug trial. Perhaps there is a lesson to be learned. When dealing with a disease and serious as MS, open lable sounds more fair and humane. The participant knows up front the drug may or may not help but might be better than the alternative. Just my thoughts...

Although I understand the ethics of enrolling people in placebo-only groups, not everybody WANTS to take a CRAB. I have a problem with clinical trials that investigate a new treatment + CRAB plus CRAB only. There needs to also be the new treatment-only group, because without it, we won't know whether a new treatment is at least comparable to a CRAB and maybe better. This is important, because some existing drugs or agents like statins, Vitamin D, antibiotics, etc being tried out on MS patients might be at least as good as a CRAB, a whole lot easier to take with fewer side effects, not to mention much less expensive. Some people have tried CRABs and can no longer tolerate them. And new treatments yet untried possibly have unfavorable interactions with CRABs, as suggested by Tysabri, but may not have such serious adverse effects when taken alone and may be better than anything yet tried. Or, the treatment plus CRAB may produce a better result than CRAB only or treatment only, which is why I think the treatment plus CRAB group should also be in a trial.

From all the posts on this site, I believe there are enough people with MS that either don't want to take a CRAB, or who no longer can take a CRAB, that would be willing to be in the new treatment-only group. Those currently on CRABs and doing okay with them can be a pool for the treatment plus CRAB participants. Others can run as CRAB-only. Nobody wants to be in a straight placebo group, and perhaps straight placebos are not necessary at this point because we want to see if we can improve on the CRAB. Without a straight placebo, there is no choice but to run the CRAB and the new treatment against each other in two separate groups, with CRAB plus new treatment as the third group.

I appreciate that the pharmaceutical companies have invested a lot in the CRABs, but that shouldn't trap everyone into a CRAB being the only option for treatment or clinical trial participation for years to come. I consider that unethical.

Lisa

Tovaxin may or may not be the improved treatment we are waiting for. But the limited data to date suggests that it is good at limiting relapses and allowing some repair to take place. Unfortuntately, time is not on our side given the degenerative nature of this disease. We may well have to wait 3 years to see Tovaxin hit the market (if at all). Surely, there must be ways to speed up the process of promising treatments - and I'm not talking Tysabri or cutting corners.

The way trials are currently constructed seems to me to ensure that they take a long time and that the results are never that clear. We know what the CRABs can do - 30% average reduction in relapses. I've seen no evidence that they stop people progressing to SP, or that they promote repair (seen through reduction of EDSS). The CRABs have had their day but annoyingly (like a bad smell) stick around. There must be scope for undertaking a trial without a placebo or one of the CRABs.

Tovaxin could be trialled with an appropriate sample of sufferers and at key points, the revelant data would be know e.g. % had no relapses in the first year; x% had an improvement of X points on EDSS scale by end of month 12; X% reduction in inflammatory lesions etc etc. I do not need to be confused by the inclusion of CRABs - I know their effectiveness.

I think safety is important, but I also think about Jacqueline de Pre or Richard Pyror. Time is not on our side and I'm sure that many of us would take the risk to gain some benefit. Others might wait until all the safety issues have been bottomed out - but by that time the promising treatments may be too late for them! One MS presenter at a drugs conference said - 'I want to add life to my time, not time to my life'. I couldn't agree with him more.

In a consumer society we are being offered very little choice at present - four drugs - each offering an effectiveness of around 30%. But what we are being offered is not what we are after - which is halting the disease, gaining back functions etc. In any other market it would be investigated by the competition commission. But MS is always differen!

I think Lisabee is onto something: coming up with creative ways of having different groups in a trial that won't necessarily involve placebo or CRABs. I don't think CRABs should always be part of a trial, but there are some people who would prefer that type of trial and some who wouldn't. It makes sense that some trials include them and some don't. In terms of improving of the CRABs, I agree that we do want to know if something works better than the CRABs, but that is NOT all that counts now. As you point out, a lot of people either don't respond to the CRABs or can't tolerate them. For these people, an alternative to the CRABs that works as well, or not even as well, is still a potential option if there are no alternatives. Finally, since the effectiveness of the CRABs seems to vary from trial to trial and CRAB to CRAB, we can't even say exactly how effective a new treatment might be if it's compared to CRAB. I hate the idea of being on a placebo, but it does make for the most scientifically sound trial methodology as far as I can tell. Maybe we just need to make the placebo groups a smaller percentage of the trialists.

Interesting abstract of a paper by the Sylvia Lawry group on using statistical models instead of placebo groups:

http://www.slcmsr.net/download/publikat ... 003_MS.pdf