FDA study shows Tovaxin decreased MS attacks by 92%

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 will say a little about the treatment in this email. More information and a list of FAQs can be found on my small website that show my timeline of events in the study. http://www.ihavems.com

The company making the vaccine, 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 FDA has approved Phase IIb/III trials for Tovaxin, which will start in the first quarter of 2006. There will be 30 sites throughout the US. There should also be sites in Canada and outside of North America. I will paste in a press release about that and the inclusion and exclusion criteria for the next study. There will be several other FDA studies of Tovaxin starting next year. If you don't fit the criteria for this study, there will be other studies for all age groups, levels of disability, and types of MS.
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, and in the same way that a flu vaccination works, the body treats these T-cells as a foreign invader and makes antibodies to eliminate only these specific T-cells. These antibodies eliminate all of the myelin reactive T-cells. 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.
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. The company has a nice animation of how Tovaxin works at http://www.pharmafrontierscorp.com/toxavin.php If you have a dialup connection, this may take 20 minutes to download, but it is worth the wait.When I started the study in November 2003, my EDSS was 5.5. It is now 3.0. 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 had a thread "Tovaxin new MS vaccine" going on Montel's Corner of SpotLight on Health, where I discussed being in an FDA trial for Tovaxin. The whole site has been down for at least a month, and I don't know if it will ever return. Because of that, I have decided to post on or email some sites about Tovaxin. Since the study I am in is an FDA phase I/II trial, you may not have seen anything about Tovaxin. I decided to make my participation in an FDA trial public since I could not find anyone in a trial that was posting a complete timeline of what went on in a study. I hope that my describing every step, test, and result will better inform people of what goes on. This may be of use when deciding if you want to be a human lab rat.

Best regards, Tim
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http://www.findarticles.com/p/articles/mi_m0EIN/is_2005_Oct_3/ai_n15656722
Note: There is a pesky popup if you use the link to this article.

PharmaFrontiers Presents Positive Tovaxin™ Research at International Multiple Sclerosis Meeting
Business Wire, Oct 3, 2005
THE WOODLANDS, Texas -- PharmaFrontiers Corp. (OTCBB:PFTR), 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.
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21st Congress of the European Committee for the Treatment and Research in Multiple Sclerosis10th Annual Meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis
http://registration.akm.ch/einsicht.php?XNABSTRACT_ID=12064&XNSPRACHE_ID=2&XNKONGRESS_ID=22&XNMASKEN_ID=900
Friday, September 30, 2005, 15:30 - 17:00
Autologous T cell therapy in multiple sclerosis: an open-label safety and dose-range studyB. Loftus, M. Montgomery, J. Williams (The Woodlands, Texas, 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.
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http://www.mstrust.org.uk/news/recentstories/article.jsp?id=753
PharmaFrontiers Tovaxin phase IIb multiple sclerosis clinical trial protocol accepted by FDA
2005-10-31
PharmaFrontiers Corp, a company involved in the development and commercialization of cell therapies, announced today that the protocol for its Phase IIb clinical trial of Tovaxin, a novel T cell therapeutic vaccine for Multiple Sclerosis (MS), has been accepted by the U.S. Food and Drug Administration's (FDA) Center for Biologics Evaluation and Research (CBER).
"PharmaFrontiers is very excited to receive a 'green light' from the FDA for our Phase IIb clinical trial. Our earlier open-label Phase I/II clinical trials not only gave us the safety and tolerability data we sought, but we also observed a trend towards a reduction in annualized relapse rate (ARR) in excess of 90%, the lowering of the myelin-peptide reactive T cells (MRTCs) in patients blood and the improvement in patients' clinical measures," said David B. McWilliams, chief executive officer of PharmaFrontiers. "The Tovaxin clinical program continues to show promising results and we believe that the completion of this Phase IIb clinical trial will allow us to launch a Phase III pivotal trial."
Tovaxin is a trivalent formulation of attenuated 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. MRTCs are believed to play a critical role in the pathogenesis of MS. Because several myelin antigens are described as potential autoantigens for MS, depletion of MRTCs using a trivalent formulation may have enhanced therapeutic effects.
This multicenter, randomized, double blind, placebo-controlled Phase IIb clinical study is designed primarily to evaluate the efficacy, safety and tolerability of the Tovaxin T Cell therapy with clinically isolated syndrome (CIS) and early relapsing-remitting MS (RR-MS) patients. Additionally, the study of these patients will evaluate biomarkers of Tovaxin's efficacy and to evaluate the effect of Tovaxin on immune deviation and epitope spreading.
"We believe that the protocol design will allow us to study the clinical effects of Tovaxin in a group of patients requiring a safe and effective therapy," said Edward J. Fox, M.D., Ph. D., director of The MS Clinic of Central Texas (Austin) and the lead principal investigator for the upcoming clinical studies. "During this two-arm, 52-week, parallel-group study, patients will be given five subcutaneous injections at 0, 4, 8, 12 and 24 weeks. The analyses will be performed at the end of the 52-week study to assess the safety and efficacy of Tovaxin. The primary efficacy variable is the cumulative number of gadolinium-enhancing lesions on T1-weighted MRI summed over the Week 28, 36, 44, and 52 MRIs. The secondary efficacy variables are the cumulative number of new gadolinium-enhancing lesions at Weeks 28-52, the change in T2-weighted lesion volume, and the annualized relapse rate. Of the 150 patients participating in the trial, 100 will receive Tovaxin and 50 will receive the placebo."
All patients who complete the trial will be eligible to participate in an optional one-year extension study, in which they will receive Tovaxin open-label. The open-label study is being planned under a different protocol that will be submitted to the FDA.
"A patient-specific therapeutic vaccination strategy, Tovaxin T cell vaccine is formulated using the MS patient's own myelin peptide-specific activated T cell lines, which are harvested and attenuated on the day of vaccine administration," said Jim C. Williams, Ph.D., PharmaFrontiers chief operating officer. "The shelf-life of the final product is approximately three days."
PharmaFrontiers will be conducting the Phase IIb with its clinical development partner, INC Research, Raleigh, NC.
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The inclusion and exclusion criteria for the next study

There will be several other FDA studies of Tovaxin starting next year. If you don't fit the criteria for this study, there will be other studies for all age groups, levels of disability, and types of MS. 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.

Eligibility
Ages Eligible for Study: 18 Years - 45 Years
Genders Eligible for Study: Both
CriteriaInclusion Criteria:
Age 18 to 45 years old Diagnosis of MS within the past 3 years according to the McDonald criteria (2001) Baseline EDSS score between 0 and 3.5 inclusively
Exclusion Criteria:
Unable to produce T cell vaccine Disease-modifying treatment for MS during the last 60 days Diagnosis of progressive-relapsing, secondary progressive or primary progressive MS Planned pregnancy Any prior treatment with total lymphoid irradiation, cladribine, T cell or T cell receptor vaccination
Location and Contact Information

Please refer to this study by ClinicalTrials.gov identifier NCT00245622

Shannon M Inman MSBlood@pharmafrontierscorp.com