Phase 1 Dose Escalation Study

A Phase 1 dose escalation study was conducted in Relapsing Remitting Multiple Sclerosis (RRMS) and Secondary Procession Multiple Sclerosis (SPMS) patients who were intolerant or unresponsive to current approved therapies for MS. The 2.5 year, open-label, dose escalation study evaluated safety and clinical benefit by administering a primary series of 4 treatments at one of 3 dose levels administered at baseline, weeks 4, 8, and 12.

Conclusions

Results of the efficacy analyses provide evidence of the effectiveness of Tovaxin in the treatment of MS. Statistically significant improvements from baseline at both week 28 and week 52 were observed in Annualized Relapse Rate (ARR). Evaluation of Multiple Sclerosis Impact Scale (MSIS-29) suggests a trend for Tovaxin therapy in the improvement of physical parameters assessed by the MSIS-29. For the Expanded Disability Status Scale (EDSS), statistically significant improvements in comparison to baseline were observed at weeks 12 and 20. The 3-4.5 ◊ 107 cell dose level appears to be the most desirable because of the 100% percent reduction in ARR at both week 28 and week 52 and the consistent reduction of autoreactive T-cell counts at each time point.

Subjects showed statistically significant improvement in overall reduction of Myelin Reactive T-cell (MRTC) counts over baseline at all visits through week 28, as assessed by total MRTC count percentage changes. These data indicate that Tovaxin treatment causes a depletion or immunomodulation of these cells, most obvious at time points more proximal to the injections. This study provided important proof of concept data for Tovaxin.

Overall, results of the safety analyses indicate that treatment with Tovaxin is well-tolerated. Reported adverse events were mostly mild or moderate in intensity. Mild injection site reactions were observed but all resolved rapidly without treatment. In conclusion, data from this study suggest that Tovaxin is safe for the treatment of MS.

Phase 1/2 Extension Study

The second clinical study performed by Opexa was an open-label extension study to treat patients who were previously treated with T-Cell vaccine but whose MS disease had clinically worsened while off Tovaxin, Protocol Number 2001-01. The purpose of this extension study was to continue evaluating the efficacy, safety and tolerability of Tovaxin in patients with RRMS and SPMS with repeated administration of Tovaxin.

Conclusions

Results of the analyses provide evidence of the effectiveness of Tovaxin in the treatment of multiple sclerosis with repeated dosing. Statistically significant improvements from baseline at both week 28 and week 52 were observed for the frequency of MS exacerbations, annualized relapse rate (ARR). Evaluation of MSIS-29 component scores suggests a trend for Tovaxin therapy in the improvement of physical and psychological parameters assessed by the MSIS-29. The EDSS score analysis revealed an upward trend for the percentage of subjects that reported improvement and sustained improvement over baseline as a result of Tovaxin treatment.

Subjects showed statistically significant improvement over baseline in the MRTC counts for each time point through month 9 of the study. These results indicate that Tovaxin treatment results in a statistically significant impact on these cells.

Overall, results of the safety analyses indicate that repeated treatment with Tovaxin is well-tolerated. Reported AEs were mostly mild or moderate in intensity. Mild injection site reactions were observed but all resolved rapidly without treatment.

In conclusion, results from this study suggest that repeated dosing of Tovaxin has a significant effect in reduction of annualized relapse rates in subjects with MS and was well tolerated.

Long-term Follow-up of Pooled Data from Phase 1 and Phase 1/2

A two-year pooled analysis was performed to longitudinally evaluate the tolerability and clinical benefit to second year re-treatments with Tovaxin. The analysis pooled 22 patients that had participated in either the Phase 1 Dose Escalation study or the Phase 1/2 Extension study. Each individual study allowed for re-treatment after one year of treatment. Patients were then assessed for another year for a total of two years after treatment. Of the 22 pooled patients, 13 patients were diagnosed as Relapse Remitting Multiple Sclerosis (RRMS) and 9 were Secondary Progressive Multiple Sclerosis (SPMS) at the time of study entry.

After the first annual course of treatment the company conducted an analysis of each patientís specific disease profile and myelin peptide epitope profile using Opexaís proprietary Epitope Analysis Assay (EAA). The analysis showed that 19 of the 22 patients (86%) had undergone an epitope shift, or change in disease pattern since the original course of treatment. Based on the epitope analysis, Opexa manufactured a new and specific vaccine for each of these patients for their second course of treatment. This enabled Opexa to tailor each vaccine to the individualís current disease profile, thereby maximizing the potential effect.

Results

The two-year, long-term, analysis demonstrated a statistically significant decrease in the Annualized Relapse Rate (ARR) from baseline of 82%, p=<0.0001 (from 1.38 to 0.21 relapses/patient/year). In addition, 73% of the group remained relapse free after two years and 86% demonstrated no worsening of disease (27% of these showed sustained improvement in disability as measured by EDSS). The immunological analysis showed a decreased number of circulating pathogenic Myelin Reactive T-Cells (MRTCs) without the presence of any detectable reduction in the general lymphocyte populations. Side effects observed over the two year treatment period have been limited to moderate injection site reactions, with no serious adverse events, observed by the principal investigator, to be related to Tovaxin treatment.

Conclusion

In Conclusion, Tovaxin represents a safe and effective treatment for MS. Results from this long-term pooled analysis suggest that Tovaxin has a significant effect in reduction of annualized relapse rated in subjects with both relapsing-remitting and secondary-progressive forms of MS. The lack of generalized immune suppression observed at this stage of development is one important aspect that distinguishes the safety of Tovaxin from certain marketed drugs.