Opexa Therapeutics Reports Positive Top-line Data in Phase I/II Dose Escalation Trial with Tovaxin(TM) for Multiple Sclerosis
03 April 2007
Opexa Therapeutics, Inc, a company involved in the development and commercialisation of cell therapies, today announced positive top-line data in an open-label Phase I/II dose escalation clinical trial of the investigational T-cell vaccine, Tovaxin(TM), for multiple sclerosis. In this one-year, 10-subject dose escalation clinical trial, Tovaxin therapy was shown to be safe and effective. The "per-protocol" analysis of Tovaxin therapy achieved a 90% reduction (p = 0.0039) in annualised relapse rate (ARR) in subjects who received one of the three dosage levels; the doses were 6 - 9 x 10(6), 30 - 45 x 10(6) or 60 - 90 x 10(6) attenuated T-cells. Subjects in the study received subcutaneous injections of Tovaxin over a period of 20 weeks (0, 4, 12 and 20 weeks) and were monitored for an additional 32 weeks.
The safety profile for all dosage levels revealed no severe adverse reactions related to T-cell vaccination. With increasing dosage, an increase in mild injection site reactions was observed and these resolved within 48 hours.
All subjects currently are enrolled in an extension study to collect longitudinal safety and effectiveness data.
David McWilliams, president and chief executive officer of Opexa, commented, "We are particularly encouraged by the data from this dose escalation trial. While all three dosage levels were safe and effective, the group treated with the 30 - 45 x 10(6) T-cell dose achieved a 100% reduction in ARR. The currently enrolling Tovaxin IIb clinical trial is being conducted with the 30 - 45 x 10(6) T-cell dose."
The Tovaxin Phase IIb clinical study will include 150 patients in a multicenter, randomised, double blind, placebo-controlled trial designed primarily to evaluate the efficacy, safety and tolerability of the Tovaxin T- cell vaccination with clinically isolated syndrome (CIS) and relapsing-remitting MS (RR-MS) patients. A total of 100 patients will receive Tovaxin, while 50 will receive placebo. The study is designed as a two-arm, 52-week, parallel-group study, whereby 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 scans 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 annualised relapse rate. As of March 19, 2007, Opexa reported that more than 110 patients have been enrolled in the TERMS clinical trial and the Company expects enrollment to be complete by mid 2007. All patients who complete the trial will be eligible to participate in an optional one-year extension study, in which they will receive Tovaxin under an open-label protocol. The open-label study is being planned under a different protocol that will be submitted to the FDA.
About T-cell Vaccination
For a T-cell vaccine to be effective, it should be able to induce T-cell cytotoxic and/or regulatory immune responses against the pathogenic T-cells. Studies of T-cell vaccine have indicated that T-cell vaccination with peripheral blood-derived autologous myelin-peptide selected T-cells in multiple sclerosis patients resulted in the in vivo induction of CD8+ cytotoxic T-cells and CD4+CD25+FoxP3 Tregs specific for T-cell vaccine. The induction of anti-idiotypic cytotoxic CD8+ effector T-cells and anti-ergotypic CD4+CD25+FoxP3 positive Tregs is believed to provide a therapeutically effective dual mechanism of protection to patients treated with Tovaxin(TM). The observed regulatory immune responses have been shown to collectively correlate with clinical improvement in treated patients.
Source: Opexa Theraputics