This Is MS Multiple Sclerosis Community: Knowledge & Support

No, I didn't mean to imply that improving on a CRAB is the only thing that matters, but we all would like at least that much. I don't know of anyone that loves injecting CRABs. My gut feeling is that if a drug or treatment is a totally new, still unproved therapy, it should be run against a straight placebo, perhaps in some manner as the stat paper posted suggests, with a combination of historical data and a small randomized placebo group. Ethically, as suggested already, there should be some markers of improvement apparent within 6 month to one year, so one does not get a placebo longer than that and for some people one year is pushing it. I think it is too risky to have people on a CRAB also getting tested with an experimental drug or procedure whose effects in humans is largely unknown. Tovaxin would fall into this category, as did (after the fact) Tysabri. I don't think Tovaxin testers are taking people on CRABs in their trials, although I could be wrong.

However, if the study is for an existing drug, dietary supplement, etc whose adverse effect profile is better known and which is not expected at the outset to have adverse interactions with a CRAB (although this is not ever really known until tested), then such an agent could be run against a CRAB and also possibly a CRAB+agent combo. We are all holding out for a cure, or next best, total control of the disease process. The next best thing down from that would be drugs at least as effective as what is out there now that are easier to take and tolerate.

Lisa

I read the posts above, and the links.

Within in that I keep reading 92% effective. I was wondering if anyone has links to hard numbers of how many people were in the trial? I read that the 8% failure was due to one person having one relapse.

This treatment sounds pretty promising.

When are the Phase III trials planned? or have they finished? I have read that it isnt expected that this treatment wont be widely available untill 2007 / 2008.

They are planning a Phase IIb trial starting early in 2006. This trial runs for about a year I think. Hopefully that means that they can start a Phase III trial by late 2007, which means if all goes well, the earliest it might see approval is late 2010.

The two links about the new study:
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http://www.clinicaltrials.gov/ct/show/N ... 22?order=1

The Phase I/II study was an open label, most likely small, study. I.e., as good as the treatment may be, the trial results and the 92% are not proof of anything.

The new study IIb will have an enrollment of 150. But it looks like a 50/50 split between placebo and and the real treatment. Given that it is a one year study, it may be a bit hard to get that many volunteers even with all the new hype about the treatment and true desperation out there. May be, they are just going for the CIS crowd which would tend to skew the results. I.e., The earlier one applies any treatment the better the trial results will tend to be.

However, it does look like a treatment with potential.

-Gary

Hi to all,
The FDA has approved the phase IIb clinical trials protocol and patient enrollment will begin in Austin and Houston Texas before the end of the year. Other sites will begin enrollment after the first of the year. If you fit the eligibility criteria and are interested in being in the study, you should use the contact information posted on the government clinical trials site (below). There will be sites throughout the US and some in Canada. There should also be some sites outside of North America.

If you don't fit the eligibility criteria for this study but are interested in being in the next study, you should still contact the company and have them put you on the list for the next study. 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 are several more studies that are in the works. The company wants to show that this works with all of the different types of MS, the different age groups, and the different levels of disability.

Best regards, Tim

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Press release on FDA approval
October 31, 2005 04:00 AM US Eastern Timezone

PharmaFrontiers Tovaxin(TM) Phase IIb Multiple Sclerosis Clinical Trial Protocol Accepted by FDA

THE WOODLANDS, Texas--(BUSINESS WIRE)--Oct. 31, 2005--PharmaFrontiers Corp. (OTCBB: PFTR), a company involved in the development and commercialization of cell therapies, announced today that the protocol for its Phase IIb clinical trial of Tovaxin(TM), 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.

About PharmaFrontiers Corp.

PharmaFrontiers' strategy is to develop and commercialize cell therapies to treat several major disease areas such as cardiac and pancreatic conditions and Multiple Sclerosis. PharmaFrontiers owns patented and proprietary individualized cell therapies that are in FDA Phase I/II human dose ranging clinical trials to evaluate their safety and effectiveness in treating MS. The company also holds the exclusive worldwide license from the University of Chicago, through its prime contractor relationship with Argonne National Laboratory, for patents relating to the use of adult pluripotent stem cells derived from patients' own circulating blood.

Safe Harbor Statement

This press release contains "forward-looking statements," including statements about PharmaFrontiers' growth and future operating results, discovery and development of products, strategic alliances and intellectual property, as well as other matters that are not historical facts or information. These forward-looking statements are based on management's current assumptions and expectations and involve risks, uncertainties and other important factors, specifically including those relating to PharmaFrontiers' ability to obtain additional funding, develop its stem cell technologies, achieve its operational objectives, and obtain patent protection for its discoveries, that may cause PharmaFrontiers' actual results to be materially different from any future results expressed or implied by such forward-looking statements. PharmaFrontiers undertakes no obligation to update or revise any such forward-looking statements, whether as a result of new information, future events or otherwise.

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http://www.clinicaltrials.gov/ct/action ... CEDAA4DBDE

Autologous T Cell Vaccine for Multiple Sclerosis

This study is not yet open for patient recruitment.
Verified by PharmaFrontiers Corp October 2005

Sponsored by: PharmaFrontiers Corp
Information provided by: PharmaFrontiers Corp
ClinicalTrials.gov Identifier: NCT00245622


Purpose

A 1 year study to evaluate the efficacy, safety, and tolerability of Tovaxin T cell therapy in subjects with Clinically Isolated Syndrome (CIS) and Relapse-Remitting MS (RR-MS)
Condition Intervention Phase
Clinically Isolated Syndrome (CIS)
Relapse-Remitting Multiple Sclerosis (RR-MS)
Vaccine: Autologous T cell vaccine
Phase II


MedlinePlus related topics: Multiple Sclerosis


Study Type: Interventional
Study Design: Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efficacy Study

Official Title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of Subcutaneous Tovaxin in Subjects With CIS or RR-MS

Further Study Details:
Primary Outcomes: To evaluate the efficacy, safety, and tolerability of Tovaxin TCV in subjects with CIS or RR-MS
Secondary Outcomes: To evaluate biomarkers of efficacy of Tovaxin TCV and effects of Tovaxin TCV on epitope spreading
Expected Total Enrollment: 150
Study start: December 2005
Last follow-up: July 2007

A 2 arm, 52 week parallel-group of Tovaxin versus placebo in subjects with CIS or RR-MS. Subjects who provide written, informed consent will complete screening and procurement assessments and provide blood to be used for vaccine production. Eligible subjects will be enrolled to receive either Tovaxin or placebo and will complete baseline assessments. Randomization and enrolled subjects will receive study treatment by subcutaneous injections at weeks 0, 4, 8, 12, and 24. Subjects will be monitored by CBC, serum chemistries, urinalysis, EDSS, MSFC, MSQLI, MRI, and monitor myelin reactive T cells for safety, efficacy, and tolerability of Tovaxin.
Eligibility

Ages Eligible for Study: 18 Years - 45 Years, Genders Eligible for Study: Both
Criteria
Inclusion 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 281-719-3405 MSBlood@pharmafrontierscorp.com



Study chairs or principal investigators

Edward J Fox, M.D., Ph.D., Principal Investigator, Central Texas Neurology Consultants
Jim C Williams, Ph.D., Study Director, PharmaFrontiers Corp
More Information

Study ID Numbers: TERMS Study; 2005-00
Last Updated: October 27, 2005
Record first received: October 20, 2005
ClinicalTrials.gov Identifier: NCT00245622
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-10-28

Hi to all,

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.

The company will start enrolling patients after the first of the year. There will be 30 sites in the US. There should be some sites in Canada and outside of North America.

Merry Christmas to all, Tim

thanks, just to let you know we appreciate you keeping us up to date.

Hi to all,

I have a new website with lots of FAQs. I took about 500 emails questions and made more than 40 FAQs from them. The site is currently http://www.ihavems.org but I will point ihavems.com at it as soon as I do some final tweaks.

Best regards, Tim

Thanks Tim, I always look forward to your updates.

J

Tim,

Next time you visit the clinic bring back a syringe full of the stuff for me.

The initial results (reduction in relapses and reduction in EDSS) look promising and it's good to see a real person rather than a statistic. Are others on the trial seeing similar effects?

It's a shame that it will be some time before this treatment is widely available, particularly given the limited efficacy of the CRAB drugs.

Have a good Christmas.

Ian

PS There's a two week stay in historic London if you can get me on the trial.

Ian, assuming tovaxin trial proves sustained efficacy with few or no side effects, when is the earliest we could expect widespread availability? Is 2008 too unreasonable to hope for?

thanks

J[/quote]

Brownsfan,

I am not Ian and I’m sure he will answer you shortly.

I personally think that 2008 is too early to see widespread availability. Tovaxin needs to complete a phase IIb (1 year) and then a phase III (at least 2 years) in clinical trials before it is approved. I am as eager as you are to see better medications approved but even if Tovaxin performs very well in clinical trials, I think 2008 is unfortunately too early to hope for.

Hi Ian,

I know you are joking, but even if I could get you a syringe full, the key point about Tovaxin is that the vaccine is MY vaccine and probably wouldn't be of any benefit to anyone other than me. I believe that the T-cell vaccine platform that Dr. Zhang created will be able to cure all of the other autoimmune diseases -- rheumatoid arthritis, Crohn's, type one diabetes, lupus, etc.

Even though I have had remarkable results, Tovaxin does need to show those same improvements in a wider patient base. If it is fast-tracked, it might be out in 2009, but 2010 is more likely. I present my story so that people wanting to be a lab rat have a little more information upon which to base their decision. The new FAQ section on my site http://www.ihavems.com answers a lot of questions, and I do respond (slowly) to posts on this site.

Merry Christmas to all, Tim

Tim

Thank you for this valueable information. Your progress is excellent news.

Best of luck and a merry christmas to you too.

J.

I'm very excited about the development of Tovoxin and I looked up information about the company on the internet. They have a very interesting website and filmclips about Tovoxin and MS.

On their news page they mention that they have just bought exclusive worldwide license for the intellectual property rights and research results of an autologous T cell vaccine for rheumatoid arthritis from the Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences of the People's Republic of China.

I've also looked up the financial information about this company. While the Tovoxin info is promising, the financial condition of this company is not. Some very basic thumbnail math suggestes that something needs to change soon at Pharmafrontiers in order to continue to pay for the work they are doing. This concerns me. They are spending money buying a license to a Chinese drug when this company doesn't seem to have enough money to fund the work it has taking Tovoxin to the next Phase.

What happens to companies that run out of money? What happens to the research and those who are participating in trials, etc.? Kim