Fox et al. A randomized clinical trial of autologous T-cell therapy in multiple sclerosis: subset analysis and implications for trial design. Mult Scler J. 2011 [Epub ahead of print]
Background: Tovaxin is an designer T-cell immunotherapy (tailored to each individual) under investigation for the treatment of MS. The product consists of in vitro expanded (grown in cell culture), myelin-reactive T-cells manufactured to react with up to six parts of three different myelin proteins. The production renders the cells unable to grow but is geared to make the body produce regulatory cells that control T cells reacting to the myelin proteins
|Fig: T cell (purple) interacting with an antigen presenting cell; T cell vaccines are meant to change how these T cells get activated.|
Methods: A Phase 2b placebo controlled study (TERMS) was conducted in 150 subjects to gather safety and efficacy data in relapsing-remitting MS and clinically isolated syndrome subjects.
Results: Tovaxin had a favorable safety profile. Although no statistically significant clinical or radiological benefit of Tovaxin immunotherapy was identified in the modified intent-to-treat population, a prospective analysis of subjects with more active disease favored Tovaxin in terms of annualized relapse rate (ARR) and disability progression. An analysis also found a possible legacy effect of prior disease-modifying treatment (DMT) which may have contributed to a lowered ARR in the placebo group. DMT-naïve subjects treated with Tovaxin had a lower ARR compared to the placebo group, particularly in those with active baseline disease (ARR≥1, ARR>1). However, clinical benefit was not was accompanied by a treatment-dependent improvement in MRI measures.
Conclusions: Previous DMT exposure may reduce effect size and study power. Limiting subject selection to DMT-treatment-naïve individuals may be a reasonable approach to phase 2 or proof-of-concept studies of limited duration.
"Phase II trials are geared to detect whether a treatment is safe rather than to show a treatment effect, which is the aim of the phase III study. However, rather than conclude that people who have previously been treated do not do relapse as much as those who have not been treated, I would suggest that the study provides no evidence that the drug works!