TERMS Phase 2b overview

Opexa completed the 150 patient Tovaxin for Early Relapsing Multiple Sclerosis (TERMS) Phase 2b clinical study in late 2008 which was one of the first clinical studies investigating an autologous T-cell therapy in MS patients. The purpose of this study was to evaluate the efficacy, safety and tolerability in patients who have been diagnosed with Relapsing Remitting MS (RRMS) or Clinically Isolated Syndrome (CIS) . Patients were administered Tovaxin or placebo at weeks 0, 4, 8, 12, and 24. The randomization was stratified by disease type (RRMS vs. CIS) as well as the presence of gadolinium (Gd+ vs. Gd-) enhancing lesions with brain MRI at screening, with a 2:1 ratio (Tovaxin:placebo). The effectiveness of Tovaxin treatment in comparison to placebo was measured by changes in brain MRI, relapse rate and disability over the course of the one year study.

Data from this clinical study show compelling evidence that a subgroup of Relapsing Remitting MS (RRMS) patients treated with Tovaxin saw overall clinical, MRI, and immunological benefits over the placebo group. Patients with more active disease, those with an Annualized Relapse Rate (ARR) more than one at baseline, experienced a statistical significant decrease in Annualized Relapse Rate (ARR), improvement in disability score (EDSS), and improvement in quality of life measures (MSQLI) as compared to placebo-treated patients. Tovaxin was found to have an excellent safety profile with no serious adverse events related to Tovaxin treatment.

Phase 2b Results

The 12-month analysis of the Phase 2b TERMS study demonstrated a number of positive outcomes. Data in patients with at least one relapse in the 12 months prior to study entry (ARR >1; representing 86% of total study population) showed:

• More than 83% of Tovaxin-treated patients remained relapse free at one year
• 42% decrease in ARR following treatment compared to placebo, yielding an ARR=0.20
• 73% of Tovaxin-treated patients showed stabilization or improvement in MS disability including 16.5% with a sustained improvement in the Expanded Disability Status Scale (EDSS) of at least one full point.

All analyses of the TERMS study data have shown Tovaxin to be safe and well tolerated with no serious adverse events related to Tovaxin treatment. Mild injection site reaction was the most common adverse event. Although the study did not show statistical significance in its primary endpoint (cumulative number of gadolinium enhancing lesions summed over weeks 28 to 52), the analyses of the prospectively identified group of patients (ARR>1; n=50) and an additional sub-population including patients with more active disease (ARR>1; n=129) were promising and warrant further development of Tovaxin.

TERMS Design

The Phase 2b Tovaxin for Early Relapsing Remitting MS (TERMS) trial was a multi-center, randomized, double-blind, placebo-controlled study in 150 patients with Relapsing-Remitting Multiple Sclerosis (RRMS) or Clinically-Isolated Syndrome (CIS). It was conducted in 33 sites in the United States. Of the 150 patients enrolled in the study, 100 received Tovaxin and 50 received placebo. Subjects received either five subcutaneous injections of Tovaxin at a dose of 30-45 X 10⁷ cells in a 2mL dose or placebo at weeks 0 (study initiation), 4, 8, 12, and 24.

Phase 2b Conclusions

Based on the current safety data, Tovaxin continues to be safe and well tolerated with minimal adverse events without any serious drug related toxicities. 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.

Tovaxin demonstrated strong efficacy in the group of patients with more active disease across several key endpoints including a reduction in Annualized Relapse Rate (ARR), an improvement in disability (as measured by EDSS), reduction in brain atrophy and reduction in progression to black holes. Along with MRI data suggesting a reduction in neuronal cell loss, these results raise the possibility that Tovaxin-treatment may have neuroprotective as well as disease-modifying effects.

Tovaxin’s favorable safety profile and these early efficacy signals strongly support moving forward with clinical development.