PharmaFrontiers Presents Positive Tovaxin(TM) Research at International Multiple Sclerosis Meeting
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.
“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”
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.
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. The company 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. PharmaFrontiers also 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.
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