Opexa Therapeutics, Inc, a company which develops and commercialises cell therapies to treat autoimmune diseases such as MS, rheumatoid arthritis, and diabetes, said the independent Data Safety Monitoring Board (DSMB) of its ongoing 150-patient phase IIb safety and efficacy study (TERMS) of Tovaxin in multiple sclerosis recommended that the trial be continued as scheduled.
Opexa's Data Safety Monitoring Board is an independent group of multiple sclerosis experts which is responsible for monitoring the ongoing safety and conduct of the study. At each DSMB meeting, the board may recommend continuing the trial unmodified, continue the trial with modifications or discontinue the trial.
The DSMB meeting reviewed 28-week data for approximately 50 per cent of the patients in the study. The DSMB noted in their report very few dropouts and that the study appears to be proceeding well. In addition, the report indicated that baseline MRI data is consistent with the assumptions used in the design of the study. Edward Fox, M.D., Ph.D. said, "As the lead investigator of the TERMS trial, I continue to anticipate the conclusion of this experimental protocol, which has been designed to evaluate the efficacy, tolerability, and safety of Tovaxin in the treatment of patients in the early stages of Multiple Sclerosis."
David McWilliams, president and chief executive officer, Opexa Therapeutics, said, "I am pleased by the steady progress of the trial and the recommendation of the DSMB. We have delivered all Tovaxin doses to patients in the study and now look forward to presenting 52-week topline results of the TERMS phase IIb study in September. With this report, we are aggressively moving forward with our regulatory plans and furthering our discussion with potential strategic development partners."
The descriptive analysis provided to the DSMB included clinical laboratory results, adverse events, vital signs and physical examination data as well as the cumulative number of gadolinium-enhancing lesions on T1-weighted MRI scans, the cumulative number of new gadolinium-enhancing lesions, the change in T2-weighted lesion volume, and annualized relapse rates. Disease progression, as measured by changes in disability scores using the industry-standard Kurtzke Expanded Disability Status Scale (EDSS) along with other select qualitative/quantitative MS-specific instruments, was also assessed.
The Tovaxin phase IIb clinical study includes 150 patients in a multicentre, 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 annualized relapse rate.
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. The observed regulatory immune responses have been shown to collectively correlate with clinical improvement in some patients treated in earlier clinical studies.